Efficacy and safety of single pill combination of amlodipine and valsartan in hypertensive Saudi patients.

OBJECTIVE: A significant global health issue that affects 25.5% of Saudi people is hypertension (HTN). According to international recommendations, most HTN patients require more than one therapy to reach their blood pressure targets (BP). Therefore, it would be preferable to utilize two medications from distinct classes separately or in a predetermined combination. According to recent studies, a single-pill combination (SPC) may be more efficient. This study evaluated the safety and tolerability of Amlodipine/Valsartan (Aml/Val) SPC in Saudi hypertensive patients, as well as the effectiveness of the medication. PATIENTS AND METHODS: Observational research was done prospectively at the King Fahad Armed Forces Hospital in Jeddah, Saudi Arabia. The effectiveness of the treatment and the percentage of 159 hypertensive patients who achieved the target blood pressure values (140/90; 130/80 mmHg) among those with diabetes mellitus (DM), chronic kidney disease (CKD), other cardiovascular disorders, and responders were assessed from the beginning to the endpoint (week 23). RESULTS: According to the results, taking Aml/Val SPC significantly lowered all patients' baseline systolic and diastolic blood pressure readings by -17.97 and 8.58 mmHg, respectively. 43.4% of patients successfully met their BP therapeutic objectives by bringing their blood pressure levels back to normal, including 51.4% of patients under 65, 39.3% of patients with chronic kidney disease, and 26.2% of diabetic patients. Aml/Val 10/160 mg significantly lowers SBP, more than Aml/Val 5/160 mg (-13.32% vs. -9.00%, p<0.050). Vertigo (6.30%), respiratory tract infections (4.0%), and ankle edema (2.50%) were the most frequent adverse events. CONCLUSIONS: Aml/Val SPC therapy effectively lowered BP and had few side effects while being well-tolerated in people with hypertension.

The correlation between copy number variation in Chromosome 14 and DNA methylation in Saudi autistic children.

OBJECTIVE: Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder that represents a range of aberrant behaviour symptoms such as repetitive behaviours and defects in social communication. The prevalence of ASD has been increasing worldwide and many studies have reported that both genetic and epigenetic factors play an important role in the etiology of this disorder. The aim of this study was to investigate the implementation of DNA methylation and Copy number variation (CNV) in the diagnosis of ASD. PATIENTS AND METHODS: This study was carried out on 14 Saudi autistic children and four of their healthy siblings. Comparative genomic hybridization array was used to identify CNV in chromosome 14 and MethyLight qPCR was used to estimate levels of DNA methylation. RESULTS: The results identified CNVs in six cytobands in chromosome 14 for 13 out of 14 autistic samples: 14q11.1-q11.2, 14q11.2, 14q12, 14q21.1, 14q32.2, and 14q32.33. However, some of these cytobands were also found in normal samples with different sizes. Interestingly, chromosomal abnormalities in 14q11.1-q11.2 was only found in ASD samples. The result also showed an increase in methylation ratio of ASD samples in those CNV regions compared with their siblings. CONCLUSIONS: The findings suggest that CNV in 14q11.1-q11.2 might be a potential target in ASD diagnosis and further work is required to detect which biological pathways are affected.

Flow cytometric analysis of CD4 and T-lymphocytes of chronic amphetamine and alcohol abuse.

INTRODUCTION: Drug and alcohol abuse has significant negative impacts on individuals' life, health status and communities. They have also been implicated immunity system diseases. Therefore we aim to investigate the impact of chronic amphetamine abuse or co-abuse of alcohol with amphetamine on immunity, especially CD3 T cells, as well as the response of CD4 and CD8 T cells. PATIENTS AND METHODS: A research sample comprising of 53 individuals younger than 40 years of age was employed to perform a retrospective case study within the setting of the Al-Amal Psychiatric Hospital. Individuals were distributed into 3 groups as the following: group (i) 17 patients abused amphetamine only for five years, group (ii) 17 patients' co-abused alcohol and amphetamine or five years, and group (iii) composed of 19 non-abusers of similar age and sex was selected as control. Flow cytometry was conducted for the collection and analysis of CD3+CD4+ and CD3+CD8+ monoclonal antibodies from blood samples. RESULTS: In contrast to the control group, amphetamine abuser patients showed a significantly decrease of the mean levels of CD3+CD4+ (#Event), CD3+CD8+ (#Event) and CD3+CD8+ (% Total). Meanwhile, levels of CD3+CD4+ (% Parent) was significantly higher in patients versus control (P = 0.001). furthermore, In the amphetamine abuse patient group, there were significant positive correlations between CD3+CD4+ (#Event) and CD3+CD4+ (% Total); CD3+CD8+ (#Event); Between CD3+CD4+ (% Parent) and CD3+CD8+ (% Parent) and CD3+CD8+ (% Total); Between CD3+CD4+ (% Total) and CD3+CD8+ (#Event); Between CD3+CD8+ % Parent) and CD3+CD8+ (% Total). CONCLUSION: The present work shed light on the reaction of CD4 and CD8 T cells to chronic amphetamine and alcohol abuse, which was found to induce changes in the systemic immune response. Interestingly, amphetamine abuse markedly changes the systemic immune as they diminished CD3+CD4+ and CD3+CD8+ T cells, and amphetamine and co-abuse alcohol affected CD3 cells significantly.

Evaluation of the role of an antioxidant gene in NSC-34 motor neuron-like cells as a model of a motor neuron disease.

BACKGROUND: Spinal muscular atrophy is a rare genetic disease, which primarily affects motor neurons and predominantly occurs in children. To date, alternatives for the treatment of the disease have been controversial. Spinal muscular atrophy has a multi-factorial aetiology, with mitochondrial oxidative stress considered as the crucial pathogenic mechanism. To determine the mechanisms underlying the loss of motor neurons, NSC-34 motor neuron-like cells are often used as an in vitro model of spinal muscular atrophy. As plastin 3 (PLS3) has been demonstrated as a modifier of spinal muscular atrophy, the aim of the current study was to evaluate the neuroprotective effect of PLS3 in NSC-34 cells. MATERIALS AND METHODS: Plastin 3 was overexpressed in human embryonic kidney 293T cells and NSC-34 cells via lentiviral transduction. NSC-34 cells transduced with a lentiviral vector carrying the gene for LacZ ß-galactosidase served as a control. Oxidative stress was then induced by depriving cells of serum, and the protective effect of PLS3 was assessed using a cellular reactive oxygen species detection assay. RESULTS: While PLS3 was successfully overexpressed in human embryonic kidney 293T cells and NSC-34 cells, upregulation of this protein did not significantly decrease oxidative stress in serum-deprived NSC-34 cells relative to controls. CONCLUSIONS: Plastin 3 overexpression in NSC-34 cells did not elicit an antioxidative effect following serum deprivation.

The effect of prolonged formalin fixation on the staining characteristics of archival human brain tissue.

BACKGROUND: Neurodegenerative disorders include wide range of conditions, which affect millions of people worldwide. Unfortunately, they are incurable and irreversibly progressive. Immunohistochemical staining of paraffin-fixed tissues for both diagnostic and research purposes are widely used. However, large amount of brain tissues are fixed but little is known about whether they are suitable for retrospective studies. The study aimed at investigating the effects of prolonged formalin fixation time on immunohistochemical expression of some common neurodegenerative markers in archival brain specimens. MATERIALS AND METHODS: Twenty brain specimens were obtained from hu- man cadavers in the Anatomy Department of King Abdulaziz University that were prefixed in 10% formalin. They were divided into two equal groups according to time of fixation: group 1 - less than 1 year, group 2 - up to 20 years. Histological examination of white and grey matter was done using haematoxylin and eosin, luxol fast blue (LFB) for myelin staining, Con- go red for amyloid plaques, CD 68 for microglial cells, tenascin-C (large ex- tracellular matrix glycoprotein) and caspase 3 antibody for apoptotic cells. RESULTS: For both groups, corpus callosum sections displayed myelination with LFB staining. The distribution of CD 68 positive microglial cells was evi- dent in frontal and temporal grey matter, but not in corpus callosum sections. Strongly positive masses were seen in Congo red-stained frontal and temporal sections. Anti-caspase 3 immunostaining revealed positively stained neurons. CONCLUSIONS: Histological and immunohistochemical techniques yielded repro- ducible staining results when applied to human brain tissue stored in formalin for long periods; so they can be used in well preserved biobank material which are the most targeting research areas in neuropathology.