Pharmacology

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https://hdl.handle.net/20.500.11888/17721

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    DOWN-REGULATION OF BETA-CATENIN IN CANCER CELLS BY SIRNA COMPLEXED WITH CARBON NANOTUBE
    (2023-03-14) Ahmad Ghareeb
    Globally, according to the World Health Organization, cancer is the second leading cause of death worldwide. In order to manage cancer, many approaches have been used, such as surgery, radiation, chemotherapy, and gene therapy. Medicine research has taken advantage of biotechnology-based therapy in the past several years, and one of the newest strategies in cancer therapy; is the utilization of small interference RNA (siRNA) to control gene expression. However, effective delivery of siRNA into cells is a challenge, particularly in vivo. Lipofectamine is currently used in vitro for this purpose, but unfortunately, the compound has demonstrated unacceptable toxicity in vivo. To deliver these types of molecules without causing significant harm, researchers are developing new technological delivery systems. The development of drug delivery systems based on carbon nanotubes (CNTs) has received a lot of attention in this respect. Our project aims to develop a new method for delivering siRNA into colon cancer cells in order to target the expression of the β-catenin protein, which is known to play a role in a variety of developmental processes; such as cell growth and proliferation, embryonic patterning, cell differentiation, and other cellular functions. The new approach is based on the synthesis of a new nano-system of multi-walled carbon nanotubes (MWCNTs) functionalized with a tetra-amine linker and mannose sugar as a targeting agent to increase the nano-system`s uptake and selectivity. We successfully functionalized MWCNTs with tetra-amine groups (f-MWCNTs (8)), which were then functionalized with mannose molecules (f-MWCNTs (12)), confirmed by atomic force microscopy. In addition, the amount of amine in f-MWCNTs (8) was 12.7 x 103 nmol/mg and 40 x 103 nmol/mg in f-MWCNTs (12), while the amount of loaded mannose in f-MWCNTs (12) was 20.02 μg/mg as confirmed by the anthrone method. The N/P ratio required to trap β-catenin siRNA starts at 5:1 for f -MWCNTs (8) and 15:1 for f -MWCNTs (12), as determined by agarose gel. Western blot analysis revealed that our compounds significantly reduced β-catenin protein expression (p > 0.05). The knockdown percentage was 20% in f-MWCNTs (8) and 50% of f-MWCNTs (12). We hypothesized that the possible up-regulation of mannose receptors on the surface of caco-2 cells may increase the transfection efficacy of f-MWCNTs (12) compared with f-MWCNTs (8). The MTS results showed that the down-regulation of β-catenin protein can restrict cancer cell growth and prevent cell proliferation which was shown significantly in both transfection approaches with an IC50 equal to 66.48 for f-MWCNTs (8)-siRNA slightly lower than control (IC50 = 70.01μg/ml) while 19.32 μg/ml for f-MWCNT (12)-siRNA. Also, this effect can increase the efficacy of 5-FU in colon cancer significantly compared with control. Therefore, we propose that our approach could be implemented in the setting of colon cancer therapy. Keyword: Beta-catenin; Colorectal Cancer; Multi-walled Carbon Nanotubes.
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    DRUG UTILIZATION PATTERN AMONG TYPE II DIABETIC PATIENTS IN PALESTINE
    (2023-09-24) Mai Ayed Ahmad Awad
    Background: Diabetes mellitus is a type of frequent metabolic illnesses that leads to hyperglycemia from a number of different pathogenic pathways. Drug utilization studies on anti-diabetic agents is essential for encouraging responsible drug use and providing useful data for health planning. Objective: This study aims to describe the drug utilization and the drug description pattern of Type 2 Diabetes Mellitus (T2DM) in Palestine and determine whether it follows the international guidelines of taking hypoglycemic medications in T2DM specially the initial drug prescribed after diagnosis with T2DM mainly in patients treated in diabetic health care centers in MOH. Methods: A cross-sectional survey was conducted in patients treated in diabetic health care centers in Ministry of Health (MOH). The study participants were selected randomly, and 400 patients were interviewed from the diabetic clinics in the northern and middle areas of the West Bank, Palestine. All ethical guidelines were taken into consideration in this study. Results: The results showed that 400 patients were interviewed, 138 (34.5%) were males and 262 (65.5%) were females. The mean age of the patients is 60 years old. The most initial drug prescribed for diabetic patients was metformin. The study's adherence showed that 68% of patients take their medicines as directed yet 24% occasionally forget. Also, vast majority of diabetic patients (about 90%) follow their prescribed medication regimen, taking the recommended dosage exactly as indicated and neither more nor less. Our analysis's findings indicated that there isn't a statistically significant difference in the way that metformin is prescribed in various areas. Glimepiride prescriptions, however, differed statistically significantly (p=0.01) throughout the areas that were visited. Conclusion: Findings of the study have revealed that the most often used medication was metformin as initial therapy, followed by glimepiride. Combination treatment was more frequently used. Therefore, steps may be taken to promote rational prescription by studying the present prescribing practices. Keywords: Drug utilization review, Diabetes mellitus type II, oral hypoglycemic agents, hyperglycemia.
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    EVALUATION OF INFLAMMATORY BOWEL DISEASE SEVERITY, TREATMENT AND OUTCOMES AMONG PALESTINIAN PATIENTS
    (An-Najah National University, 2024-02-01) Naser, Aya
    background Inflammatory bowel disease (IBD) is considered a chronic disease, and it has become more widespread recently. Studies related to it in Palestine are limited. The objectives of this study are to evaluate the severity of the disease, its treatment, and its outcomes among Palestinian patients with inflammatory bowel disease to improve its treatment and follow up. Method This cross-sectional study was conducted from August 2022 to March 2023 at An-Najah National University Hospital, Nablus, Palestine. A data collection form was used to collect data from patients’ files and interviews, it was designed to assess IBD severity, treatment, and outcome. The results were analyzed using the Statistical Package for the Social Sciences (SPSS). Result This study included 219 patients 53.4% of them were males and 46.6% were females, the duration of illness 1-38 years, the age ranged between 6-86 years. we found that 47.9% patients suffered from ulcerative colitis and 52.1% from Crohn's disease, regarding severity of the disease which was based on clinical and diagnostic characteristics, patients were diagnosed with mild in 26% cases, while 45.2% had moderate, and 28.8% were diagnosed with severe. Moreover, the most common symptoms were bloody diarrhea 63%. Regarding medications, mesalamine was the most common medication used as a primary medication in patients with IBD, at a rate of 74%. for current medications, mesalamine was used by 46.6%, corticosteroid by 22.8%, azathioprine by 41.1%, and biological therapy by 35.2%. Conclusion Many patients have severe stages of the disease which affects their daily life. this study shows number of significant associated factors that should be considered when dealing with IBD. Results of the study may help healthcare providers and strategy makers to increase knowledge about IBD patients and its treatment, to improve the quality of life of the IBD patient.
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    EVALUATION OF SAFETY AND EFFICACY OF PHARMACOLOGICAL AND NON-PHARMACOLOGICAL TREATMENTS USED BY IRRITABLE BOWEL SYNDROME PATIENTS
    (An-Najah National University, 2024-10-14) Sarhan, Reem
    Background: Many people in Palestine suffer from irritable bowel syndrome (IBS). Some people deal with the disease using medications, while others prefer non-pharmacological treatments and avoid food that aggravate the symptoms. Objectives: The study aims to assess the severity of IBS, the lifestyle the patients live and evaluate the safety and efficacy of pharmacological and non-pharmacological modalities to treat irritable bowel syndrome among Palestinian patients. Methodology: This was a cross-sectional study using a data collection form to collect data from patients by a face-to-face interview. Patients were met from gastroenterology outpatient clinics, community pharmacies and hospital pharmacies in Bethlehem. The Statistical Package for Social Sciences was performed using statistical analysis (SPSS version 21). Results: A total of 407 patients with irritable bowel syndrome in Bethlehem and surrounding areas participated in this study. The mean age was 36.87±13.8 years old. Among them, 253(62.2%) were females, 263(64.6%) were married and 201(49.4%) were living in the city. Regarding clinical and disease characteristics, 258(63.4%) did not have a family history of IBS, 201(49.4%) had alternate diarrhea and constipation, 229(56.3%) had mixture of solid and watery stool, 310(76.2%) had abdominal pain, 352(86.5%) had abdominal bloating, 350(86%) had abdominal gases, and 69(17.0%) had a bloody stool. Furthermore, the disease affected patients’ life by different ways; 248(60.9%) became nervous, 129(31.7%) couldn’t sleep well. Regarding non-pharmacologic treatments, 206(75.2%) used herbs to sooth IBS symptoms, and 234(57.5%) avoided food that irritates colon. It was found that using herbs that sooth the IBS, increasing liquids, avoiding food that irritates the colon and having exercise were all significantly associated with improvement in IBS symptoms; P-values were <0.001, 0.032, 0.001 and 0.029 respectively. About pharmacologic treatments, 188(46.2%) had taken chlordiazepoxide and clinidium bromide, and 143(35.1%) had taken probiotics to treat IBS symptoms. 148(36,4%) patients told that they had full improvement from pharmacological treatments. Use of probiotics, synthetic fibers, (chlordiazepoxide & clinidium bromide) and hyoscain significantly associated with improvement in symptoms, P-values were <0.001, <0.001, <0.001 and 0.030 respectively Conclusion: Irritable bowel syndrome is a bothering problem that affects daily life, many patients try non-pharmacological treatments with accepted efficacy. Even with pharmacological treatments many patients could not attain satisfactory improvement
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    GENERATION OF ENGINEERED DERMAL TISSUES ENRICHED WITH CHITOSAN-MULTIWALL CARBON NANOTUBE COMPLEX FOR UTILIZATION IN WOUND HEALING
    (An - Najah National University, 2023-05-29) Amal Jafar Alqato
    Introduction and background: The process of wound healing is complicated and involves four precise stages: hemostasis, inflammation, proliferation, and remodeling. When interrupted, this process can result in chronic wounds, constituting significant health and economic burden. Engineered skin tissues (EST) with different constituents have been proposed as a potential treatment. Aim of the project: To generate engineered dermis tissues (EDTs) as a substitute for the dermis layer to enhance wound healing. Material and Methods: The scaffolds of the generated EDTs were based on collagen, which is similar to the natural dermis, and it was enriched with chitosan, a natural biocompatible and biodegradable polymer that possesses wound-healing properties, and different concentrations of multiwall carbon nanotubes (MWCNTs) that can enhance the mechanical properties of the EDTs. The effect of incorporating angiotensin-II (Ang II) in the tissues on angiogenesis was also investigated. All tissues were populated by 3T3 cells. The EDTs were transplanted in a mouse wound model, and the wound sites were analyzed macroscopically and histologically by masson-trichrome stain after 14 days of transplantation to evaluate the quality of wound healing. Results: Overall, our study found that transplanted tissue had no negative impact on animal health. It reduced contraction and facilitated epithelization, but did not affect the percentage of wound closure. EDTs transplantation did not affect the thickness of the new epidermis, but it increased the thickness of the dermis. The incorporation of Ang II in the matrix of the EDT did not affect the degree of angiogenesis. Conclusions and Recommendations: The transplanted tissue enhanced the quality of wound healing by promoting epithelialization and reducing contraction. This finding is significant for the development of potential treatments for slow-healing or high-risk scarring wounds.
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    PERCEPTIONS, CONCERNS AND PRACTICES OF COMMUNITY PHARMACISTS REGARDING COVID-19
    (جامعة النجاح الوطنية, 2022-08-31) Najjar, Alaa
    Abstract Background: COVID-19 is thought to be one of the serious public health hazard to date. Community pharmacists are one of the first line health care workers working hard during this pandemic, and their role is critical in preventing COVID-19 spread. Objective: This study aims to assess perception and practice of community pharmacists in Palestine towards COVID-19 pandemic and to evaluate the concern and worries of community pharmacists from COVID-19. Methods: A cross-sectional survey has been performed in community pharmacy in West Bank. The study was done from the 1st of February to the end of April 2021. A total of 314 respondents were selected by complex randomized method. The self-administered questionnaire was used for data collection. All ethical consideration were considered. Results: The results showed that 18.2% of the participants have a high-level of knowledge about COVID-19, while 69.1% have moderate level of knowledge and 12.7% have a low level of knowledge. The result showed that 87.3% of the participants have a high-level of practice related to COVID-19, while 12.7% have a low level of practice. The result showed that 30.3% of the participants had a high anxiety level while 41.4% had a moderate level of anxiety and 28.3% had a low level of anxiety. The logistic regression showed that gender affected knowledge and gender female is a risk factor. Regarding the practice, Health status affected practice, pharmacist who have a disease that increases the risk of contracting the virus were more likely to have good practice, by same away, gender female, age more than 60, the pattern of working in the morning and evening shift, address of work (central), health status (who have a disease that increases the risk of contracting the virus) and who have been diagnosed with COVID-19 is factors affected on anxiety (P<0.05). Conclusion: Our finding revealed a satisfactory perception and practice of community pharmacist towards COVID-19. But there are high levels of concern present among Palestinian community pharmacist toward COVID-19. Keywords: COVID-19, Perception, Practice, Concern, worry, Community pharmacist.
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    PHARMACOTHERAPY OF EPILEPSY IN WOMEN: CURRENT STATUS, FUTURE DIRECTIONS, AND CHALLENGES
    (جامعة النجاح الوطنية, 2022-03-31) Zaid, Lina
    Background: This study was conducted in two phases: a systematic review and a qualitative study. The systematic review was conducted to evaluate concentrations of antiepileptic drugs (AEDs) in breastmilk of lactating women with epilepsy (WWE). The qualitative study was conducted to explore the perspectives of neurologists, gynecologists, psychiatrists, internists, and pharmacists about caring for WWE in Palestine. Methods: In the systematic review, the databases: MEDLINE/PubMed, EMBASE, CINAHL/EBSCO, COCHRANE, SpringerLink, ScienceDirect, Summon, WHO International Clinical Trials Registry Platform, and SCOPUS were systematically searched. In the qualitative study, a purposive sampling technique was used to recruit the participants for the qualitative study. Semi-structured in-depth interviews were conducted neurologists (n = 6), gynecologists (n = 5), psychiatrists (n = 3), internist (n = 1), and clinical pharmacists (n = 5). The interpretive description methodology was used to thematically analyze the qualitative data. Estimated daily intake (EDI) and relative infant doses (RID) of AEDs were calculated. Results: A total of 15 records were included in this systematic review. The included studies reported levels of 8 AEDs in the breastmilk of WWE. Lamotrigine, levetiracetam, carbamazepine, topiramate, valproic acid, and gabapentin did not produce significant adverse effects that warranted discontinuation of breastfeeding. The mean EDI of AEDs ranged from 0.1 to 278.16 µg/g body weight/day and the mean RID ranged from 1.63% to 36.33%. Breastfeeding might be limited or even discontinued when signs of excessive sedation/drowsiness and/or poor weight gain are evident in infants exposed to primidone and phenobarbital, ethosuximide/primidone, or ethosuximide/phenobarbital. The following themes emerged from the qualitative data: 1) diagnosis and care for patients with epilepsy, 2) general issues in caring for patients with epilepsy, and 3) consideration of women’s issues in the pharmacotherapy of epilepsy. Conclusion: Healthcare providers and WWE might use the findings of this study to make informed decisions on the safety of breastfeeding while taking AEDs. Findings of this qualitative study showed a need to formally adopt uniform guidelines that can guide the diagnosis and care of WWE in the Palestinian healthcare system.
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    PHYSICIAN’S ADHERENCE TO INTERNATIONAL TREATMENT GUIDELINES FOR MAJOR PSYCHIATRIC DISORDERS: A DESCRIPTIVE STUDY FROM PALESTINE
    (2022-11-03) Huda Said Shebli
    Background: Psychiatric disorders are progressively considered among the common health disorders affecting people worldwide. Data from Western countries show that psychiatric disorders are relatively prevalent. Objectives: In this study, we aimed to assess the Palestinian psychiatrist’s adherence to the international treatment guidelines in treating common psychiatric disorders. In addition, we aimed to explore the factors associated with non-adherence to the treatment guidelines. Methodology: A retrospective study was conducted to examine psychiatrist’s adherence to treatment guidelines and the factors associated with the non-adherence of patients diagnosed with schizophrenia, depression, anxiety, bipolar disorder, and schizoaffective disorders, which was obtained from the period May 2021 to September 2021 in an outpatient psychiatric clinic in the north of West Bank, Palestine. Results: A total of 1070 prescriptions were examined. Most patients were aged between 36 and 55 years (47.8%), and two-thirds were males (63.8%). Most of the patients were diagnosed with schizophrenia (46%), while the rest were diagnosed with depression, bipolar disorder, schizoaffective, and anxiety (22.7%, 18.2%, 9.1%, and 4%, respectively). In general, the most commonly prescribed drugs were typical anti-psychotics (47%), followed by atypical antipsychotics, SSRIs, TCAs, BZD, anti-convulsants, and lithium (39.9%, 22.7%, 20.7%, 15.3%, 14.3%, and 3.6%, respectively). Moreover, the study showed that the majority of psychiatric prescriptions (76.8%) were non-adherent to treatment guidelines and 64.7% of them were for males while 47.5% of non-adherent prescriptions were for adult patients aged 36-55 years old. The non-adherent prescriptions were significantly higher among patients diagnosed with schizophrenia (50.73%) (p-value=0.000). In addition, the study found that the majority of non-adherent prescriptions (37%) were due to the drug’s unavailability in the psychiatric clinic. Conclusions: The pharmacotherapy of the major psychiatric disorders in Palestine was not in line with the international treatment guidelines. The most common factors which were associated with the non-adherence are schizophrenia and drug unavailability. Keywords: Adherence; Factors; Guidelines; Outpatients; Psychiatric Disorders.
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    THE RELATIONSHIP BETWEEN SYMPTOM SEVERITY AND SYMPTOM INTERFERENCE, QUALITY OF LIFE, AND TYPE OF TREATMENT IN PALESTINIAN WOMEN WITH BREAST CANCER
    (An-Najah National University, 2024-03-05) Yasin, Eman L.
    Background: Breast cancer is one of the most common cancers that affects women more than men and is considered a major cause of cancer death among women. Women with breast cancer experience bothersome symptoms related either to the disease itself or breast cancer treatments that interfere with patients’ life activities and affect their quality of life. Objectives: To provide a comprehensive explanation of the relationship between symptom severity and symptom interference, quality of life and type of treatment. Methodology: This is a cross-sectional study conducted through the MDASI questionnaire to assess symptom severity and symptom interference and the EQ-5D-5 L questionnaire to assess quality of life among women with a confirmed diagnosis of breast cancer at An-Najah National University Hospital and AL-Watani Hospital. The questionnaire was completed through face-to-face interviews and reviewing patients’ medical records. Results: A cohort of 229 participants was enrolled in the study. Predominantly, patients (34.1%, n=78) fell within the 50-59 years age bracket. Treatment modalities included chemotherapy alone (35.4%, n=81), hormonal therapy (48%, n=110), targeted therapy (9.6%, n=22), and various combination regimens. Specifically, 3.9% (n=9) received hormonal therapy along with targeted therapy, and 3.1% (n=7) underwent combined chemotherapy and targeted therapy. Fatigue emerged as the most prevalent and severe symptom, except for women undergoing chemotherapy plus targeted therapy who reported heightened complaints of sleep disturbances. Pearson correlations between the MDASI symptom severity total mean score and the MDASI symptom interference total mean score were significant for chemotherapy (r = 0.685, p < 0.05), hormonal therapy (r = 0.827, P < 0.05), targeted therapy (r = 0.922, P < 0.05) and hormonal plus targeted therapy (r = 0.699, P < 0.05), and not significant for the chemotherapy plus targeted therapy group (r=0.398, p=0.329). The most robust associations were identified with feelings of sadness (r=0.792, P< 0.05), fatigue (r=0.774, P< 0.05), and distress (r=0.743< P< 0.05). There were significant differences between study participants in relation to patient age, smoking status and treatment methods (p value<0.05), whereas other sociodemographic and clinical characteristics are not significantly associated with the total mean score of the symptom severity scale. Regarding the EQ-5D-5 L dimensions, the majority of patients reported no issues. The EQ-5D-5 L index score exhibited significant positive correlation with the EQ-VAS score (r = 0.568, P value < 0.05). Conversely, it demonstrated significant negative correlations with both the total mean score of symptom severity (r = -0.664, P value < 0.05) and the symptom interference total mean score (r = -0.651, P value < 0.05). Conclusions: The most common type of treatment associated with severe symptoms and affecting patients’ daily life activities is chemotherapy, which has no significant influence on patients’ quality of life. Fatigue was the most severe symptom associated with the breast cancer treatment method.
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    UPPER GASTROINTESTINAL COMPLICATIONS AND TREATMENT AMONG PATIENTS WITH CHRONIC DISEASES: A CROSS SECTIONAL STUDY FROM PALESTINE
    (2022-10-23) Deema Mahmoud Mustafa Tumeh
    Background: Most people, older than 60, have at least one chronic disease. Therefore, these people have no choice but to use, multiple drugs. Gastrointestinal complications occur because of the harmful effects of these chronic drugs on the stomach. Objectives: The study has assessed the prevalence of patients taking chronic drugs and suffering from upper gastrointestinal complications, the severity of these symptoms, and their taking of any gastro-protective drugs or not. Methodology: This is a cross-sectional study. A questionnaire was developed and administered format outpatient clinics at a specialized hospital. Patients with chronic diseases who were taking at least one medication were included in the study. A form was used for data collection. The Short-Form Leeds Dyspepsia Questionnaire (SF-LDQ) was used to evaluate the severity of the upper gastrointestinal symptoms. Statistical analysis was performed, using the Statistical Package for Social Sciences (SPSS) version 21. Results: A total of 400 patients with chronic diseases and using multiple medications participated in the study. Of these 53.8% were females and 56% were married, 58.5% were unemployed, and 70% were non- smokers.The mean age was 54.7±17.5. The most common comorbid diseases among the patients were diabetes, hypertension, and arthritis: 44.3%, 38%, and 27.3%, respectively. Most patients used between 2 and 4 medications daily. The most commonly used medication was aspirin. It was used by 50%, followed by atorvastatin, bisoprolol, and insulin: 29.5%, 25%, and 20.3%, respectively. Among the 400 participants, 362 (90.5%) suffered from upper gastrointestinal side effects like indigestion (66%), heartburn (77.5%), nausea (49.3%), and regurgitation (52.3%). Based on SF-LDQ scoring, of the 400 respondents, 235(58.8%), 109(27.3%) and 18(4.5%) suffered from mild, moderate and severe dyspepsia, respectively. In addition, 38 (9.5%) had no dyspepsia. About 81.3% of participants were prescribed gastro-protective medications. Proton pump inhibitors were the most prescribed group for 209 (52.3%) patients. Older age, marriage health insurance, education, smoking and ≥ 5 medications were all associated with a higher possibility of having dyspepsia; (p-value <0.05). Conclusion: Upper gastrointestinal complications among patients with chronic diseases were very common. Fortunately, the symptoms were mild in most cases. The risk increased with age and with the use of high number of medications. The use of gastro-protective agents, when needed, is important. Keywords: Chronic disease; upper gastrointestinal side effects; stomach irritation; dyspepsia;Palestine