Karbala Journal of Pharmaceutical Sciences

An Investigation of the Correlation Between the CNTNAP2 rs7794745 gene Polymorphism and Autism in Children from the Middle Euphrates Area of Iraq

Safaa Reza Mahdi AL-Safar — 2024-09-12

Background: Autism is an incurable condition that may be attributed to several factors, such as genetic predisposition and environmental influences. Multiple studies have discovered that a substantial number of genes linked to autism serve as constituents of signaling pathways that regulate the plasticity of synapses and development, hence exerting a notable impact on the origins of the illness. CNTNAP2 is increased during the initial phases of neural tube development. Given the increasing worldwide occurrence of autism, there is a growing demand for effective teaching methods and educational programs.

Methods: A case-control study recorded 90 samples, comprising 50 autistic individuals (males and females, mean age 4.5 ± 2 years) and 40 healthy youngsters (5 ± 2 years). PCR and restriction enzymes are used in polymerase chain reaction-restriction to amplify and analyze DNA sequences. PCR-RFLP genotyped CNTNAP2 at rs7794745. Genomic DNA was isolated from peripheral blood cells of healthy children while buccal cells were swapped from patients to obtain and genotype their DNA.

Results: Our results revealed that the low-frequency distribution (p-value > 0.05) of the rs7794745 SNP is statistically non-significant in ASD patients compared to healthy children.

Conclusion: Our case-control study suggests that rs7794745 polymorphism is unrelated to ASD.

The Effects of Extreme Electrospinning and Environmental Parameters on the Resulted Zein Nanofibers Formulated by the Electrospinning Technique

Mokhtar A. S. Al-Janabi — 2024-09-12

Objective: The study declares and shows the effect of electrospinning parameters, including the temperature, humidity, applied voltage, syringe gage, the distance between the needle tip and collector, and flow rate on the morphology of the resulted nanofiber using the electrospinning technique in the preparation of Zein polymer nanofibers.

Methods: The Zein nanofiber was formulated as nanofibers using an electrospinning apparatus. The nanofibers were prepared in different conditions, adjusting the parameters in each single run-in various temperatures and humidity. At the same time, the concentration of the zein polymer remained constant in all of the runs. Then, the nanofibers obtained after drying and collecting them from the aluminum foil were transferred to a tightly sealed container. The nanofiber was characterized using Attenuated Total Reflectance Infrared Spectroscopy (FTIR) to detect the presence of Zein polymer in the matrix. Then, the surface morphology of nanofibers was analyzed using the Scanning Electron Microscopy (SEM) technique. To declare the morphologic changes in the resulting nanofibers.

Results: The results indicate that some specific parameters and conditions can lead to perfectly shaped nanofibers, and applying different conditions and parameters can lead to abnormal morphological topography and electro-spraying instead of electrospun nanofibers.

Conclusions: The SEM images provided visual evidence of the change in morphology that resulted in each different run-in with different conditions and parameters.

Aim of the Study: This study aimed to identify the effect of different electrospinning and environmental parameters on the resulting zein polymer nanofibers.

Serological Evaluation of Systemic Lupus Erythematosus: Association with Disease Severity in Iraqi Patients

Fatimah Abdul Hussein Kadhim — 2024-09-12

The diagnosis, management and treatment of systemic lupus erythematosus (SLE) in clinical settings often involve serological measures of autoantibodies, specifically the anti-double stranded DNA and generally the anti-nuclear autoantibodies (ANA). It remains to be shown, however, whether these serological measures correspond with the severity classification of SLE, particularly among Iraqi patients. Here, we investigated the relationship between serological measurements of autoantibodies and complement proteins with severity classification of SLE patients. Sixty patients clinically diagnosed with SLE, along with 60 age-matched non-SLE individuals (control) were recruited in the study. Serum levels of ANA, anti-dsDNA, complement C3 and C4 were measured. The SLE patients had significantly higher mean values of ANA, anti-dsDNA, with significantly lower levels of C3 and C4 compared to those of the control (non-SLE). With respect to their SLE disease severity classification, while levels of ANA significantly increased with severity of disease (mild, 7.99±0.65 IU/mL; 9.83±0.93 IU/mL; severe, 13.70±1.60 IU/mL; p = 0.004), levels of anti-dsDNA despite increasing (mild, 33.38±2.18 IU/mL; moderate, 39.32±2.28 IU/mL; severe, 42.84±4.80 IU/mL), were not statistically significant (p = 0.101). (p < 0.05). Conversely, levels of C3 (mild, 1.19±0.05 g/L; moderate, 0.98±0.11 g/L; severe, 0.72±0.17 g/L; p = 0.009) and C4 (mild, 0.32±0.02 g/L, moderate, 0.29±0.03 g/L; severe, 0.16±0.03 g/L; p = 0.002) significantly decreased with disease severity (p < 0.05). Our findings show that although ANA and anti-dsDNA autoantibodies may be important in the diagnosis of SLE, their use in predicting the severity of the disease varies considerably, while also highlighting, the significance of complement components C3 and C4 in monitoring and predicting the severity of the disease in addition to their role in the diagnosis of SLE.

Studying the Role of L-Thyroxine in Long-Term Management of Hypothyroidism: A Comparative Analysis with Healthy Control

Nabaa Zuhair Miran — 2024-09-12

Background: Hypothyroidism, characterized by insufficient thyroid hormone production by the thyroid gland, which may lead to significant challenges to metabolic health and overall well-being. Hence, studying the intricate correlation between thyroid biological functions, metabolic pathways and treatment outcomes are crucial for patients care management. Although, recent researches have clarified the complexity between thyroid hormone levels and metabolic pathways, there are still unanswered questions about the specific mechanisms and practical implications.

Patients and methods: Across sectional study was conducted in Iraq from September 2023 to July 2022 involved 100 females with hypothyroidism undergoing L-thyroxine therapy for at least four months and 50 healthy subjects as control. Blood samples was collected after an overnight fast for plasma extraction. Various biochemical and hormonal assays were performed including TSH, TT4, FT4, TT3, FT3, TSH, fasting plasma glucose, insulin levels, HOMA-IR, cholesterol, triglycerides, HDL, LDL, VLDL, and BMI calculations for categorizations into weight groups.

Results: there were notable differences in weight, blood pressure, and BMI but not in age between patients with hypothyroidism and healthy controls. In addition, patients with hypothyroidism showed decreased FT4 levels, which suggested problems with the regulation of free thyroxine, along with increased TSH and FT3 levels, which indicated thyroid dysfunction and hyperactivity. Furthermore, patients had lower HOMA-IR indices and impaired glucose metabolism, highlighting the complex relationship between thyroid function and metabolic parameters. Patients had dyslipidemia indicated by elevated total cholesterol and triglyceride levels, and altered lipid metabolism was suggested by lower VLDL levels. Long-term L-thyroxine therapy resulted in a tendency toward lower TSH levels, with TT3 levels fluctuating over the course of treatment.

Conclusion: The aforementioned results offer fresh perspectives on the intricate relationships among thyroid function, metabolic markers, and treatment results in hypothyroidism. They underscore the necessity for additional investigation to clarify underlying mechanisms and enhance clinical management approaches.

Microsponges: An Innovative Instrument in Pharmaceutical Research

Mustafa R. Abdulbaqi — 2024-09-12

A microsponge delivery system is a novel and distinctive method of administering medications organizationally. The use of microsponge medication delivery enables efficient and prompt regulation of drug administration.

Microsponge delivery system consists of porous microspheres that vary in sphere size range (5 to 300 µm). These microspheres have a significant porous frame and a small spherical form. Microneedle drug delivery systems are typically used for drug administration via the skin, although they lately show potential for drug transfer through the mouth, eyes, and injection routes. Microsponge delivery systems can readily alter the pharmacological release pattern and enhance the stability of the formulation while simultaneously reducing the adverse effects of the medicine.

The primary objective of microsponge medication delivery is to achieve the greatest peak plasma concentration in the bloodstream. The most notable characteristic of Microsponge delivery systems is their inherent ability to self-sterilize.

In conclusion, the microsponge delivery system has been extensively studied and shown to have antiallergic, antimutagenic, and nonirritating properties. This study covers the formulation, criteria for medication inclusion in microsponge delivery systems, formulation techniques, evaluation parameters, and the function of microsponge delivery systems in treating different illnesses. This study will be valuable for examining the usage of microsponge delivery systems in various diseases.

Molecular Docking Study of Five Novel 1,2,3-Triazole Linked Metronidazole Derivatives as Cytotoxic Agents

Haider Hassan Al Sayad — 2024-09-12

Background: Five novel synthetic 1,2,3-triazole-linked metronidazole compounds that target the tyrosine kinase of the epidermal growth factor receptor belong to the ErbB receptor family, which includes Her1 (EGFR), Her2 (erb-B2), Her3 (erb-B3), and Her4 (erb-B4). Certain human carcinomas, such as lung and breast cancer, feature cells that overexpress EGFR. This causes the anti-apoptotic Ras signaling cascade to be incorrectly activated, resulting in uncontrolled cell growth. Inhibiting EGFR TK (PDB code: 1M17) is an important target in the development of anticancer drugs since it can help prevent tumor growth and metastasis.

Materials and Methods: Using the molecular operating environment to evaluate the binding affinity of new design compounds against targeting proteins (EGFRTK). The molecular docking process predicts how molecules interact with the target enzyme, and criteria such as S-score and RMSD evaluate the docking outcomes by comparing estimated and experimental structures. It is an extremely useful tool for drug discovery and studying molecular interactions.

Results: The newly synthesized compounds (I-V) demonstrated improved binding energy (S.score) ranging from -7.5733 to -8.4456 Kcal/mol and reduced rmsd values ranging from 0.8752 to 1.6182 with the enzyme active site, as compared to erlotinib's binding energy of -7.7359 Kcal/mol and rmsd value of 1.720.

Conclusion: The docking results demonstrated that all synthesized compounds (I-V) had higher energy of binding (S-score) and lower Root Mean Square Deviation (RMSD) values, indicating theoretical potential as effective EGFR inhibitors when compared to the reference ligand (erlotinib)

Attitudes on Diabetes Among Type 2 Diabetic Patients in Karbala City

Bashar Khaldoon Gheni — 2024-09-12

Background: Diabetes is a serious health problem that has reached an alarming scale, with over 500 million individuals affected globally. Type 2 diabetes is the most common type of diabetes, accounting for over 90% of all diabetes worldwide. The Middle East and North Africa (MENA) region has the greatest regional prevalence of diabetes (16.2%) and the second-largest expected increase (86%) in the number of people with diabetes.

Objective: This study aims to assess the attitude toward diabetes among type 2 diabetic patients in Karbala City and the factors associated with their attitude.

Patients and methods: A cross-sectional study was conducted on 252 type 2 diabetic patients in multiple health institutes in Karbala City through face-to-face interviews using a questionnaire developed by the University of Michigan Diabetes Research and Training Center (MDRTC). SPSS version 22.00 was used to perform statistical analysis. The means of the groups were compared using independent samples t‑test and ANOVA. Pearson’s rank correlation coefficient test was used to show relationships between diabetic attitude scores, glycated hemoglobin, fasting blood sugar, and random blood sugar.

Results: The mean age of the patients was 56 ± 9.83 years. 64.3% of the patients were female. The mean duration of diabetes was 10.1 ± 6.82 years. The mean attitude score for the patients was 31.55 ± 6.18 out of 50. The majority of patients (72.6%) had a moderate attitude level.

Conclusion: Continuous education programs and healthcare attention are needed to enhance patients' attitudes toward the disease and its complications, especially female patients, those with low educational levels, housewives, those not working, those with lower economic status, those with longer diabetes duration, those who take insulin as treatment, and those who have complications.

Association of FTO Gene Variants with Some Biochemical Markers of Type 2 Diabetes Mellitus Patients in Iraqi Population

Zaid Abdul-Hussain Kadhim — 2024-09-12

Background: The Fat-mass and obesity associated (FTO) gene modulates the gene expression through methylation–demethylation modifications since it is part of Fe (II) - and 2-oxoglutarate-dependent dioxygenases superfamily. This study was carried out in the Department of Clinical Laboratories / College of Applied Medical Sciences / University of Kerbala during the period from November 2022 to April 2024. The study aimed to investigate the association between the variation in the FTO gene and serum level of some biochemical markers in Type 2 Diabetes Mellitus Patients within the Iraqi Population.

Patients and Methods: One hundred volunteers participated in this study, 50 individuals with Type 2 DM as a patient’s group (25 females and 25 males), and 50 apparently healthy individuals as a control group (25 females and 25 males). The ages of all participants were ranged between 25 to 75 years at the time of the investigation. We investigate three sites in the FTO gene (FTO 1, FTO 2, and FTO 3). The variation of the FTO gene was investigated by the Sanger sequencing method. The levels of biochemical markers were measured in blood serum.

Results: The results of the present study identified the presence of four previously registered variants in FTO gene. These variants might be of interest to FTO gene studies due to their presence in the coding regions that included in the gene expression.

Conclusion: The two variants, 53769662 T/A and 53782363 C/A, may be the most important variables because there are statistical associations with some biochemical markers.

The Association of Five Novel Variants of TLR7 Gene with Some Biochemical Markers in Breast Cancer Patients from Iraqi Women

Zahraa Majid Chasib — 2024-09-12

Background: The TLR7 gene carries multiple polymorphisms that are likely associated with human diseases, including cancer. The study aimed to shed light on the relationship between the variation of the TLR7 gene and serum level of biochemical markers (CA15-3, CEA, CA125, and CA27-29) in Iraqi women with breast cancer.

Methods: a case-control study involving 100 women volunteers: 50 with breast cancer as a patient group and 50 who appeared to be healthy as a control group. The ages of all participants were ranged between 29 to 75 years. This study was conducted from November 2022 to April 2024 at the Department of Clinical Laboratories, College of Applied Medical Sciences, University of Kerbala . Sanger sequencing was used to investigate variants of the TLR7 gene. The enzyme-linked immunosorbent assay (ELISA) method was used to evaluate the levels of CA15-3, CEA, CA125, and CA27-29 in serum.

Results: Presence of 5 novel unregistered variants in the Intron 2 region. It was found that a significant effect of TLR7 - 12871749 G\C variant (SNP) of the Intron region on serum level of CEA (point biserial correlation coefficient =-0.396, p-value=0.03). A significant effect of TLR7 - 12871764 A\G variant of the Intron region on serum level of CA 15-3 (point biserial correlation coefficient =-0.385, p-value=0.03). The results showed no significant, weak, moderate, or strong associations between all other types of variants when tested individually and the four biochemical markers under study.

Conclusion: Among the five new variations, 12871749 G\C and 12871764 A\G may be the most significant variants because there is a statistical association with some biochemical markers, therefore, Future research should delve deeper into the role of TLR7 polymorphisms in the fields of tumor immunology, which may open new perspective in early diagnosis and prevention of cancer.

Evaluation Of E-Selectin Levels in Iraqi Patients with Acute Coronary Artery Syndrome

Saif Saihood Hateb — 2024-09-12

Background: There is a great deal of mortality and morbidity associated with various cardiovascular diseases that comprise acute coronary syndrome (ACS). One crucial factor in the development of ACS is inflammation of the coronary plaque. Cell adhesion molecules play a key role in the inflammatory cascade. The vascular endothelium is directly affected by elevated levels of pro-inflammatory cytokines and other systemic inflammatory markers in ACS related to atherogenesis. This causes an increase in the expression of adhesion molecules, such as selectins.

Objective: This study aims to document the inflammatory response after acute coronary syndrome by evaluating the association between serum E-selectin levels and the risk and severity of acute coronary syndrome.

Materials and Methods: A case-control study involving 120 male subjects aged 41–70 years, who were divided into two groups: 60 ACS patients and 60 healthy individuals as a control. Serum E-selectin levels were measured using an ELISA technique.

Results: The study revealed a significant increase in serum E-selectin levels when comparing patients to the healthy control group (216.07±20.26 pg/ml Vs 179.74±53 pg/ml, P ≤ 0.0001) respectively. The analysis of the receiver operating curve (ROC) for E-selectin showed a sensitivity of 85%, a specificity of 70%, a 95% confidence interval (CI) of 0.673-0.863, and the area under the curve (AUC) was 0.768. The cut-off point was set at 197.37 pg/ml or higher.

Conclusion: Elevated serum E-selectin levels in ACS patients suggest a potential role for adhesion molecules in the pathogenesis of ACS. Adhesion molecules could be considered as a biochemical marker for assessing ACS.

Effect of Genetic Polymorphism of CYP2C8 Enzyme on the Montelukast Therapy Responses in Iraqi Asthmatic Children

Hasnaa Haider Mohammed — 2024-09-12

Background: Some reports show that the CYP2C8 enzyme plays an influential role in montelukast metabolism, and genetic polymorphism of CYP2C8 genes may influence therapeutic responses of asthmatic children to montelukast treatment.

Aim of the study: The current study aimed to detect the effects of genetic polymorphism of the CYP2C8*1B (rs7909236) gene on montelukast response in asthmatic children.

Methods and Patients: An observational cross-sectional study was carried out in the respiratory clinic center in the Kerbala Teaching Hospital of Children from early October 2022 to late September 2023.

The trial included one hundred children older than six years old with asthma who had been previously diagnosed and were taking montelukast every day for at least one month. Alle-specific PCR patients out following DNA extraction to determine each patient's genotype to determine each patient's genotype. Total serum Ig E levels, Asthma Control Test (ACT), FEV1, and PEF of Pulmonary Function Tests were also measured.

Results: The distribution of CYP2C8*1B (rs 7909236) genetics polymorphism was found to be 74% for CC wild homozygous, 22% for CA mutants heterozygous, and 4% for mutants homozygous AA, according to the results of genetic amplification. Patients with wild-type and mutant genes do not significantly differ in serum total IgE, FEV1, PEF values, or ACT scores. Therefore, this polymorphism and montelukast responsiveness is predicted to be not significantly related (p value<0.05).

Conclusions: The montelukast respond and the CYP2C8*1B g.-271 G>A (rs7909236) genetic variation did not significantly associate.

Signature of IL-33 and Leptin as Early Progression Markers in Rheumatoid Arthritis

Ahmed Jawad — 2024-09-12

Background: Rheumatoid arthritis (RA) is a chronic, inflammatory, autoimmune disorder characterized by progressive and irreversible joint damage as a consequence of sustained synovitis. Adipokine levels and interleukin have been reported to be significantly increased in serum and synovial fluid (SF) of RA patients.

The study aimed to investigate the association between the levels of Leptin in the circulation of individuals with rheumatoid arthritis (RA).

Methods and Patients: The present work included a case-control study for a group of (90) samples: (60) patient samples and (30) healthy control samples. Patients with Rheumatoid arthritis were selected from Imam Hassan al-Mujtaba Hospital in Kerbala. The sociodemographic aspects of the patients were collected through the self-reported technique (student questionnaire). All patients underwent clinical history, clinical examination, and relevant laboratory investigations. The degree of rheumatoid was identified based on the evaluation of laboratory measurements for the clinical assessment of rheumatoid arthritis. An enzyme-linked immunosorbent assay system (ELISA) was performed using the sandwich-ELISA method to measure the concentrations of serum IL-33. At the same time, a competitive enzyme immunoassay kit was used to detect human Leptin in serum samples quantitatively. Statistical analysis was performed, and the efficiency of the predicting value was assessed using the receiver operating characteristic (ROC) curve.

Results: Results indicated a significant difference in IL-33 and Leptin hormone levels among the study groups, which increased with increasing age, BMI, and duration of the disease. Both biomarkers showed highly significant differences in such disease and represented a risk factor. Leptin was illustrated to be a three-time risk factor for Rheumatoid arthritis disease compared to IL33. AUC analysis for IL-33 as a diagnostic parameter showed that IL-33 performs well in predicting such cases.

Conclusion: This study confirms a significant association between elevated leptin and IL-33 levels in RA patients, with leptin showing a three-fold higher risk than IL-33. Both biomarkers increase with age, BMI, and disease duration, highlighting their potential role in RA progression and diagnosis.

Extraction, Isolation, Purification and Identification of Caffeine in Zamioculcas Zamiifolia L. Leaves Cultivated in Iraq

Estabraq Hussein Naser — 2024-09-12

Background: Phytochemical analysis of Zamioculcas zamiifolia has revealed the presence of alkaloids, phenols, flavonoids, endogenous metabolites, vitamins, carotenoids, and tannins. phytochemical profile of Zamioculcas zamiifolia holds promise for discovering new therapeutic agents and natural products. Caffeine is a purine alkaloid, its trimethyl xanthine compound that has stimulant effect on central nervous system.

Materials and Methods: the fresh leaves of plant were extracted by harborne extraction method in reflux apparatus by using ethyl acetate, chloroform, chloroform- methanol, and distilled water and then determine compounds preliminary by using specific tests through phytochemical assay and TLC. Further phytochemical investigation of compounds performed by using GC-MS, FT-IR, melting point, HPLC, and Mass spectrometer.

Results: the results exhibit different fractions as ethyl acetate, chloroform, chloroform: methanol, chloroform and distilled water weighed 0.92, 0.19,1.51, and 28.65 gram respectively, also the presence of alkaloids specifically purine alkaloids, terpenoids, and phenolic compounds which show in leaves extract, in addition to the isolation of pure caffeine from chloroform-methanol fraction and this study was the first one that isolate caffeine from Zamioculcas zamiifolia in the world.

Conclusion: The phytochemical analyses results exhibit the extract fractions of Zamioculcas zamiifolia leaves indicate the plant considered as an important source of active compounds that might feeding the modern medicine with drugs especially caffeine discovering in plant. Therefore, additional researches are required to confirm the antimicrobial, anthelminthic, anti-hyperglycemic, and anti-inflammatory activities. As well as, compounds isolation, purification and even characterization are essential to make the plant has a novel important study.

Bacterial Profile and Evaluation of Cxcl10 Level in Urine Among People Suffering from Urinary Tract Infections

Alaq Ali Abdulhussein — 2024-09-12

A common bacterial infection that affects millions of people worldwide every year are infections of the urinary tract. The most frequent causes of urinary tract infections, both simple and serious, are Escherichia coli and Klebsiella pneumonia. Proteus mirabilis, Pseudomonas aeruginosa, Enterococcus faecalis, Staphylococcus aureus, and saprophylococcus saprophyticus. In the early 1970s and late 1980s, chemokines were discovered. These positively charged cytokines have molecular weights ranging from 8 to 10 kDA. Since they control immune cell infiltration and inflammatory mediator release., they are essential to the immune system. The 10 kDa interferon-gamma inducible protein of the inflammatory chemokine IP-10, (IP-10) is too referred as C-X-C motif chemokine ligand 10 (CXCL10). Assess the concentration of CXCl10 in the urine of individuals with urinary tract infections. Biomarker (CXCL10), had high-level in-patient group compared to control group which suggests an inflammatory state in these patients. the Sensitivity % of (CXCL10) marker 55.6% and the Specificity 82.2% can be castoff as markers of inflammation, progression, and complications in patients with UTI.