Optical and Electrochemical Aptasensors Developed for the Detection of Alpha-Fetoprotein.

Early diagnosis of hepatocellular carcinoma (HCC), a leading cause of cancer mortality, is decisive for successful treatment of this type of cancer and increasing the patients' survival rate. Alpha-fetoprotein (AFP) is a glycoprotein that has been currently employed as a potential serological biomarker for determination of HCC and several other cancers. Achieving highly sensitive and specific detection of this biomarker is an effective strategy to inhibit developing issues caused by the cancer. Though, traditional procedures cannot meet the requirements due to the technical drawbacks. Recently, growing number of aptamer-based biosensors (aptasensors) attracted important attention as superior diagnostic tools because of their unique properties such as high stability, target versatility and remarkable affinity and selectivity. Nanomaterials, which broadly employed in the structure of these aptasensors, can considerably enhance the detection limit and sensitivity of analytes determination. Therefore, this review selectively investigated the recent progresses in several different optical and electrochemical aptasensors and nano-aptasensors designed for AFP assay.

Effect of Pharmacist-Led Intervention on Progression of Diabetic Complications at Two Tertiary Care Hospitals of Malaysia.

BACKGROUND AND OBJECTIVE: Diabetes mellitus is a chronic disease which can lead to different complications in patients if not treated properly. An appropriate intervention from health care providers is needed to stop and decrease the progression of diabetic complication in diabetic patients. This study aimed to measure the effect of pharmacist intervention on improvement in sign and symptoms and progression of diabetic complications in diabetic patients. METHODOLOGY: Diabetic patients were randomly selected and divided into two groups from two tertiary care hospitals. Control group contained those 200 patients who were receiving usual treatment from hospitals. In contrast, the intervention group included those 200 patients who were receiving conventional treatment from hospitals together with separate counselling sessions with pharmacists from Diabetes Medication Therapy Adherence Clinic departments. The study continued for 1 year and two follow-up visits for both groups. A prevalidated data collection form was used to measure the improvement in sign and symptoms and progression of diabetic complication in diabetic patients. Statistical Package for the Social Sciences (SPSS) version 24 was used to analyze the data. RESULTS: The average hemoglobin A1c (HbA1c) values decreased up to 1.43% in the control group and 2.82% in the intervention group. The intervention group showed significant improvement in HbA1c between groups (P < 0.05). The results of univariate and multivariate regression analysis showed that a statistically significant (P < 0.001) improvement was observed in all the predictors of diabetic complications among in the intervention group when compared with the control group. CONCLUSION: Statistically significant reduction in the sign and symptoms of diabetic complications was observed in the intervention group at the end of 1 year. The progression of diabetic neuropathy was significantly reduced in the pharmacist intervention group.

Knowledge, Attitude, and Practice of Oral Hygiene Among Students of a Private University.

OBJECTIVE: The objective of the study was to evaluate the knowledge, attitude, and practice among pre-final and final year students of pharmacy, medicine, biotechnology, and business faculties about oral hygiene. MATERIALS AND METHODS: A cross-sectional observational study was conducted to evaluate the knowledge, attitude, and practice of students towards oral hygiene at a private university in Malaysia. Validated questionnaires were distributed to a convenient stratified sample of 324 students studying in the different selected faculties, namely pharmacy, medicine, biotechnology, and business, respectively. The Statistical Package for Social Science (SPSS) Version 24.0 was used to analyze the data. RESULTS: With regard to knowledge, upon evaluation, it was seen that the students of the Faculty of Pharmacy had the highest percentage of adequate knowledge, which was statistically significant with a P-value of 0.001 and the effect size of 0.246. On the evaluation of attitudes, it was seen that the Faculty of Biotechnology had the highest positive attitudes. According to race, Malay students had the highest positive attitude among all the races that participated in the study, which showed a P-value of 0.037 with the effect size of 0.034. Regarding practice, the Faculty of Pharmacy had the lowest practice compared with the other faculties. This variable had a P-value of 0.001 and showed to have significance against the practice with an effect size of 0.193. CONCLUSION: Overall, a good attitude was seen amongst the students on their oral hygiene. It was also observed that the attitude, knowledge, and practice of the students in a private university increased with an increasing level of education.

Knowledge, Attitude, and Practice about Mental Health Challenges among Healthcare Students of a Private University.

OBJECTIVE: The objective of this study was to evaluate the knowledge, attitude, and practice of healthcare students (Medicine, Pharmacy, and Dentistry) in a private university about mental health challenges (MHC). MATERIALS AND METHODS: A research cross-sectional observational was conducted to evaluate the knowledge, attitude, and practice of students towards MHC at a private university in Malaysia. A validated questionnaire was distributed to 284 students studying in three different selected faculties, namely the Faculty of Medicine, Pharmacy, and Dentistry. The Statistical Package for Social Science (SPSS) Version 24.0 was used to analyze the data. RESULTS: Upon evaluation of knowledge, male students were having less-adequate knowledge than females (P = 0.006). Malay students were having adequate knowledge than other races about MHC. Faculty of Medicine was having adequate knowledge than other faculties (P ≤ 0.001). Regarding attitude, the Faculty of Pharmacy students had the highest positive attitudes (P = 0.001). Final year students were having a more positive attitude than pre-final year students. For the evaluation of practice, the Faculty of Dentistry students had the lowest practice compared with other faculties. CONCLUSION: In conclusion, overall, good knowledge was seen among the students of the private medical university about MHC. The medical students had adequate knowledge when compared with other faculties in the university.

Assessing quality of life using WHOQOL-BREF: A cross-sectional insight among patients on warfarin in Malaysia.

BACKGROUND AND AIM: The effect of anticoagulation control on overall Health-Related Quality of Life (HRQoL) in patients taking warfarin in Malaysia has not been explored yet. Therefore, this study aimed to evaluate HRQoL among patients on warfarin in Malaysia. METHODS: HRQoL among patients on warfarin was measured using WHOQOL-BREF (World Health Organization Quality of life Assessment: Brief Version). Descriptive and inferential statistical analysis was done using Statistical Package for the Social Sciences (SPSS) version 22. RESULTS: Out of 319 patients, more female patients were observed than the males (n = 221, 69.3%, and n = 98, 30.7% respectively). Mean scores for the physical (61.14 ± 15.96), psychological (68.58 ± 16.11), social (63.55 ± 27.06) and environmental domains (62.78 ± 17.58) were observed. Statistically, a significant association was found between the comorbidities other than CVDs with health satisfaction (p = 0.002), physical (p = 0.001), psychological (p < 0.001), social (p = 0.003) and environmental domains of the WHOQOL-BREF. A weak positive correlation between overall health satisfaction and the social domain (r = 0.153) and a moderate positive correlation between the physical and environmental domains (r = 0.628) of the WHOQOL-BREF were observed. CONCLUSION: Patients had overall better perceived HRQoL scores in the psychological domain as compared with the rest of the domains of the WHOQOL-BREF. Age, gender, employment status, education level, the indication of use and duration of warfarin therapy associated with overall perceived HRQoL.

Determinants of health-related quality of life among warfarin patients in Pakistan.

INTRODUCTION: The effect of anticoagulation control on overall Health-Related Quality of Life (HRQoL) in patients taking warfarin in Pakistan has not been explored yet. Therefore, this study aimed to evaluate HRQoL among warfarin patients in Pakistan. METHODS: This cross-sectional study was conducted among patients on warfarin in Pakistan. By purposive sampling, data were collected using demographic data collection form and the World Health Organization Quality of Life: Brief Version (WHOQOL-BREF). The WHOQOL-BREF is comprised of four domains; physical, psychological, social relationships, and environment. Descriptive and inferential statistical analysis was done using SPSS version 22. RESULTS: Out of 295 warfarin patients, more females than males (<0.001) were observed (n = 184, 62.4%, and n = 111, 37.6% respectively). One hundred and eighteen (40.0%) patients were less than 30-years of age, whereas one hundred and seventy-seven (60.0%) patients were above 30-years of age. Mean scores for the physical (62.44±15.36), psychological (67.84±15.54), social (64.27±26.28) and environment domains (63.45±17.66) were observed. CONCLUSION: Patients had overall lower to moderate but satisfactory HRQoL scores in all four domains. Age, gender, employment status, education level, the indication of use and duration of warfarin therapy was associated with one or more domains of HRQoL among warfarin patients. The findings of this study would serve as a primary database for future studies. This study highlights how non-clinical factors could impact HRQoL in studied patients.

Genetic risk assessment towards warfarin application: Saudi Arabia study with a potential to predict and prevent side effects.

Warfarin doses are greatly affected by polymorphism altering cytochrome P450 2C9 (CYP2C9) and vitamin K epoxide reductase complex subunit 1 (VKORC1) gene. This study evaluated the prevalence of alleles (either single or double) and carriers of single nucleotide polymorphisms (SNPs) in both genotypes CYP2C9 and VKORC1 in alkharj area, Saudi Arabia and its association with warfarin use risk. Total 112 samples were collected and genotyped using FlexiGene DNA Kit for isolation and StepOnePlus Real-Time PCR System by TaqMan allelic discrimination methods. The results indicated the frequency of 11%, 8% and 45% for CYP2C9 *2 *3 and VKORC1-1639 G > A polymorphism. And as a combination genotype it was 15.18% For both CYP2C9 and VKORC1 polymorphism, 27.67% for CYP2C9 and 42.86% for VKORC1. Non-carriers rate came to be at 30.3%. According to previously published dosing changes in warfarin for polymorphism carriers (single-double-triple). The predicted warfarin doses reduction in order of 1-1.6, 2-2.9, 2.9-3.7 mg/day. It was found that 72.3% of the study population was carrier of a type of polymorphism, 15.18% for two types of polymorphisms. These findings predict changes in warfarin metabolism and eventually dosing alteration among patients on warfarin. Both genotypes (CYP2C9 and VKORC1) require different dosing of warfarin than non-carriers in order to minimize the risk of warfarin overdosing and avoidance of the drug-related problems (DRPs).

Experimental and clinical antihypertensive activity of Matricaria chamomilla extracts and their angiotensin-converting enzyme inhibitory activity.

Three different extracts of Matricaria chamomilla L. were evaluated for their antihypertensive activity, these extracts were total alcohol extract (Extract 1), oil extracted (Extract 2), and water lifted after oil extraction (Extract 3). Quantitative and Qualitative analyses were carried out for all extracts. The 3 extracts were proved to be safe for human use. A single oral administration of the plant extracts (200 mg/kg) decreases both systolic and diastolic blood pressure of normotensive rats after 1, 1.5, and 2 hr. Furthermore, groups treated with the evaluated extracts (100 & 200 mg/kg) or Captopril (20 mg/kg) showed a significant reduction in the elevated blood pressure and heart rate. Extract 3 showed the most antihypertensive activity. Serum biochemical parameters and lipid profile levels of treated groups were improved in comparison with induced-hypertensive untreated rats. In evaluation of oxidative damage parameters Glutathione and superoxide dismutase (SOD) in some organs, the investigated extracts or captopril restored the amount of reduced Glutathione in tissues in addition to an increase in the activity of the SOD after a significant depletion of SOD activity. In the clinical study, there was a significant dose dependent decrease in Systolic blood pressure, Diastolic blood pressure, and heart rate compared with their basal values in both normotensive and hypertensive human volunteers after oral administration of Matricaria chamomilla beverages.

Association between risk of type 2 diabetes mellitus and angiotensin-converting enzyme insertion/deletion gene polymorphisms in a Saudi Arabian population.

The link between the angiotensin-converting enzyme (ACE) insertion/deletion (I/D) gene polymorphism and the prevalence of type 2 diabetes mellitus (T2DM) developing in the Saudi Arabian population remains controversial. The aim of the present study was to evaluate the association between the ACE I/D gene polymorphism and the risk of developing T2DM and hypertension (HTN) in Saudi Arabian individuals. A total of 220 individuals consisting of 48 control subjects, 70 T2DM, 48 HTN, and 54 T2DM with HTN patients were recruited. Genotyping was performed by polymerase chain reaction initially and mistyping of the DD genotypes was conducted with an insertion-specific primer. The genotyping frequency for the II, ID and DD polymorphism of the ACE gene was 6.8, 42.6 and 48.6% in T2DM patients, 4.2, 50 and 45.8% in HTN patients, 5.6, 55.5 and 38.9% in T2DM patients with HTN and 58.3, 37.5 and 4.2% in control subjects, respectively. The frequency for the D allele was 70% in T2DM patients, 70.8% in HTN patients and 66.7% in T2DM patients with HTN as compared with 22.9% in the control subjects. The genotype and allele frequency of the ACE gene polymorphism varied significantly (P<0.05) in the patients when compared with the control subjects. The current study demonstrated that the ID/DD genotype and the D allele of the ACE gene I/D polymorphism were strongly associated with the risk of T2DM and HTN developing in a Saudi Arabian population.

Evaluation of the diuretic and urinary electrolyte effects of methanolic extract of Peganum harmala L. in Wistar albino rats.

The use of traditional medicines as a diuretic agent has been increasing in recent years. The diuretic activity of a number of plant extracts used as diuretic agents in ethnomedicine has been confirmed in experimental animals. However, despite the widespread use of Peganum harmala in traditional medicine, there is a paucity of data supporting its use as a diuretic agent. Therefore, the present study aimed to envisage the true effect and magnitude of diuresis of methanolic extract of P. harmala (MEPH) in comparison with a well-known diuretic drug furosemide using Wistar albino rats. MEPH was administered orally in three different doses (150, 300 and 450 mg/kg) to experimentally dehydrated rats. Furosemide (10 mg/kg orally) was used as a reference drug. The diuretic effect of the MEPH was evaluated by measuring urine volume, urine pH, urinary electrolyte levels, natriuretic and saliuretic effects. The urine volume (in mL) measured at 5 h and 24 h and electrolyte excretion (Na+, K+, and Cl-) at 24 h duration were measured. The urine output and urinary electrolyte excretion were found to be significantly higher in rats treated with MEPH as compared to normal rats in a dose dependent manner (P < 0.05). The results of our study were comparable to furosemide drug. Based on observed results, we can recommend that P. harmala may be an effective diuretic, however, toxicity studies should be conducted before administration.

Liposomal Aerosols of Nitric Oxide (NO) Donor as a Long-Acting Substitute for the Ultra-Short-Acting Inhaled NO in the Treatment of PAH.

PURPOSE: This study seeks to develop a liposomal formulation of diethylenetriamine NONOate (DN), a long acting nitric oxide (NO) donor, with a goal to replace inhaled NO (iNO) in the treatment of pulmonary arterial hypertension (PAH). METHODS: Liposomal formulations were prepared by a lipid film hydration method and modified with a cell penetrating peptide, CAR. The particles were characterized for size, polydispersity index (PDI), zeta potential, entrapment efficiency, storage and nebulization stability, and in-vitro release profiles. The cellular uptake and transport were assessed in rat alveolar macrophages (NR8383) and transforming growth factor ß (TGF-ß) activated rat pulmonary arterial smooth muscle cells (PASMCs). The fraction of the formulation that enters the systemic circulation, after intratracheal administration, was determined in an Isolated Perfused Rat Lung (IPRL) model. The safety of the formulations were assessed using an MTT assay and by measuring injury markers in the bronchoalveolar lavage (BAL) fluid; the pharmacological efficacy was evaluated by monitoring the changes in the mean pulmonary arterial (mPAP) and systemic pressure (mSAP) in a monocrotaline (MCT) induced-PAH rat model RESULTS: Liposome size, zeta potential, and entrapment efficiency were 171 ± 4 nm, -37 ± 3 mV, and 46 ± 5%, respectively. The liposomes released 70 ± 5% of the drug in 8 h and were stable when stored at 4°C. CAR-conjugated-liposomes were taken up more efficiently by PASMCs than liposomes-without-CAR; the uptake of the formulations by rat alveolar macrophages was minimal. DN-liposomes did not increase lung weight, protein quantity, and levels of injury markers in the BAL fluid. Intratracheal CAR-liposomes reduced the entry of liposomes from the lung to blood; the formulations produced a 40% reduction in mPAP for 180 minutes. CONCLUSION: This study establishes the proof-of-concept that peptide modified liposomal formulations of long-acting NO donor can be an alternative to short-acting iNO.

Treatment of retinitis pigmentosa due to MERTK mutations by ocular subretinal injection of adeno-associated virus gene vector: results of a phase I trial.

MERTK is an essential component of the signaling network that controls phagocytosis in retinal pigment epithelium (RPE), the loss of which results in photoreceptor degeneration. Previous proof-of-concept studies have demonstrated the efficacy of gene therapy using human MERTK (hMERTK) packaged into adeno-associated virus (AAV2) in treating RCS rats and mice with MERTK deficiency. The purpose of this study was to assess the safety of gene transfer via subretinal administration of rAAV2-VMD2-hMERTK in subjects with MERTK-associated retinitis pigmentosa (RP). After a preclinical phase confirming the safety of the study vector in monkeys, six patients (aged 14 to 54, mean 33.3 years) with MERTK-related RP and baseline visual acuity (VA) ranging from 20/50 to <20/6400 were entered in a phase I open-label, dose-escalation trial. One eye of each patient (the worse-seeing eye in five subjects) received a submacular injection of the viral vector, first at a dose of 150 µl (5.96 × 10(10)vg; 2 patients) and then 450 µl (17.88 × 10(10)vg; 4 patients). Patients were followed daily for 10 days at 30, 60, 90, 180, 270, 365, 540, and 730 days post-injection. Collected data included (1) full ophthalmologic examination including best-corrected VA, intraocular pressure, color fundus photographs, macular spectral domain optical coherence tomography and full-field stimulus threshold test (FST) in both the study and fellow eyes; (2) systemic safety data including CBC, liver and kidney function tests, coagulation profiles, urine analysis, AAV antibody titers, peripheral blood PCR and ASR measurement; and (3) listing of ophthalmological or systemic adverse effects. All patients completed the 2-year follow-up. Subretinal injection of rAAV2-VMD2-hMERTK was associated with acceptable ocular and systemic safety profiles based on 2-year follow-up. None of the patients developed complications that could be attributed to the gene vector with certainty. Postoperatively, one patient developed filamentary keratitis, and two patients developed progressive cataract. Of these two patients, one also developed transient subfoveal fluid after the injection as well as monocular oscillopsia. Two patients developed a rise in AAV antibodies, but neither patient was positive for rAAV vector genomes via PCR. Three patients also displayed measurable improved visual acuity in the treated eye following surgery, although the improvement was lost by 2 years in two of these patients. Gene therapy for MERTK-related RP using careful subretinal injection of rAAV2-VMD2-hMERTK is not associated with major side effects and may result in clinical improvement in a subset of patients.

Fasudil and SOD packaged in peptide-studded-liposomes: Properties, pharmacokinetics and ex-vivo targeting to isolated perfused rat lungs.

The present study investigated the feasibility of encapsulating two drugs, fasudil and superoxide dismutase (SOD), into liposomes for targeted and inhalational delivery to the pulmonary vasculature to treat pulmonary arterial hypertension (PAH). Nanosized liposomes were prepared by a thin-film formation and extrusion method, and the drugs were encapsulated by a modified freeze-thaw technique. The peptide CARSKNKDC (CAR), a pulmonary-specific targeting sequence, was conjugated on the surface of liposomes. Formulations were optimized for various physicochemical properties, tested for their ex-vivo and in-vivo drug absorption after intratracheal administration, and evaluated for short-term safety in healthy rats. The homogenous nanosized liposomes contained both SOD (~55% entrapment) and fasudil (~40% entrapment), and were stable at 4°C and after nebulization. Liposomes released the drugs in a controlled-release fashion. Compared with plain liposomes, CAR-liposomes increased the uptake by pulmonary endothelial and smooth muscle cells by ~2-fold. CAR-liposomes extended the biological half-lives of SOD and fasudil by ~3-fold. Ex-vivo studies demonstrated that CAR-liposomes were better retained in the lungs than plain liposomes. Bronchoalveolar lavage studies indicated the safety of peptide-equipped liposomes as pulmonary delivery carriers. Overall, this study demonstrates that CAR-liposomes may be used as inhalational carriers for SOD plus fasudil-based combination therapy for PAH.

External ophthalmomyiasis: A case report.

Ophthalmomyiasis is an infestation of the eye with larvae of most common sheep nasal botfly (Oestrus ovis). We describe a case of ophthalmomyiasis in a 50-year-old man who presented with ocular foreign body sensation, redness and tearing. The causative larvae were removed in the emergency room and sent to laboratory for identification. The patient symptoms improved after topical treatment with antibiotics-steroid combination therapy.

The gene therapy revolution in ophthalmology.

The advances in gene therapy hold significant promise for the treatment of ophthalmic conditions. Several studies using animal models have been published. Animal models on retinitis pigmentosa, Leber's Congenital Amaurosis (LCA), and Stargardt disease have involved the use of adeno-associated virus (AAV) to deliver functional genes into mice and canines. Mice models have been used to show that a mutation in cGMP phosphodiesterase that results in retinitis pigmentosa can be corrected using rAAV vectors. Additionally, rAAV vectors have been successfully used to deliver ribozyme into mice with a subsequent improvement in autosomal dominant retinitis pigmentosa. By using dog models, researchers have made progress in studying X-linked retinitis pigmentosa which results from a RPGR gene mutation. Mouse and canine models have also been used in the study of LCA. The widely studied form of LCA is LCA2, resulting from a mutation in the gene RPE65. Mice and canines that were injected with normal copies of RPE65 gene showed signs such as improved retinal pigment epithelium transduction, visual acuity, and functional recovery. Studies on Stargardt disease have shown that mutations in the ABCA4 gene can be corrected with AAV vectors, or nanoparticles. Gene therapy for the treatment of red-green color blindness was successful in squirrel monkeys. Plans are at an advanced stage to begin clinical trials. Researchers have also proved that CD59 can be used with AMD. Gene therapy is also able to treat primary open angle glaucoma (POAG) in animal models, and studies show it is economically viable.

Severe ocular injury and its management following self induced plant extracts: A case report.

INTRODUCTION: Homemade and folk remedies' use is widely practiced in under developed countries, of the used materials are plant extracts, lemon juice and some dried insect bodies. CASE PRESENTATION: We report a case of severe ocular injury and its management after self administered plants seeds in both the eyes of a 47-year-old man who had bilateral severe ocular damage after he put the seeds of a plant Lepidium Sativum (Rashad) in his eyes. He reported severe ocular pain and redness, conjunctival epithelial defect and symblepharon. A conjunctival biopsy was taken which turned out to be negative for the immunological staining studies for Ocular Cicatricial Pemphegoid (OCP). The patient's visual acuity improved from 20/40 before treatment to 20/25 after treatment with no further sequelae after 3 months follow-up. CONCLUSIONS: Self induced plant extracts can cause ocular complications. Public awareness is necessary to help in discouraging the use of these harmful plant extracts in human eyes.

Toxic effect of Cadmium found in eyeliner to the eye of a 21 year old Saudi woman: A case report.

PURPOSE: To raise the issue of increased use of traditional medicine while the Tertiary care hospitals are available to provide the appropriate care for each clinical condition. Eyeliner (Kohl) is an Arabic word denoting a fine powder with a texture and appearance similar to mascara. It is usually worn on the lid margins or inside the conjunctival sac by Middle and Far Eastern and in East Africans populations for different purposes like beauty or religious and as a treatment for many eye diseases. SUMMARY: We report a case of a lady who put traditional locally prepared eyeliner in her eye that resulted in severe corneal edema and faint scaring. On toxicology analysis it was discovered to contain toxic levels of Cadmium (Cd) and Lead (Pb). CONCLUSION: Cd is a heavy toxic metal like Pb but has never been reported as a component of eyeliners. The most likely possible cause of the corneal clinical picture in our case is due to the toxic effect of Cd found in the traditional eyeliner (Kohl) used in Saudi Arabia.