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1.
Front Genet ; 15: 1430291, 2024.
Article in English | MEDLINE | ID: mdl-39119582

ABSTRACT

Background: In Sub-Saharan Africa (SSA), cattle are crucial for socioeconomic stability yet face numerous environmental stressors such as diseases, parasites, and extreme heat within pastoral and agropastoral systems. Despite their significance, gaps remain in understanding how genetic diversity and inbreeding influence traits essential for disease resistance and environmental adaptability. This study examines the genomic adaptations that enable SSA cattle to thrive under these conditions and assesses the impact of inbreeding on such adaptive traits. Methods: We analyzed genomic data from 113 cattle across four breeds-Kuri, N'dama, Zebu-Fulani, and Zebu-Bororo-employing Runs of Homozygosity (ROH) and Integrated Haplotype Score (iHS) analyses to identify historical and recent genetic selections. Strict quality controls using PLINK software ensured accurate genomic pattern identification related to adaptation and inbreeding. Results: ROH analysis revealed islands with genes such as RSAD2, CMPK2, and NOTCH1, which are involved in immune response and cellular stress management, highlighting regions of historical selection that have likely provided adaptive advantages in overcoming environmental and pathogenic stresses. In contrast, iHS analysis identified genes under recent selection like HIPK1, involved in stress response regulation, and EPHA5, which plays a crucial role in neural development and synaptic functions, potentially equipping these breeds with novel adaptations to ongoing and emergent environmental challenges. Conclusion: This research confirms that selective pressures inherent in pastoral and agropastoral systems profoundly influence the genetic structure of SSA cattle. By delineating the genetic bases of key adaptive traits, our study offers crucial insights for targeted breeding programs to enhance cattle resilience and productivity. These findings provide a valuable framework for future genetic improvements and conservation strategies, crucial for sustainable livestock management and economic stability in SSA.

2.
J Vis Exp ; (204)2024 Feb 23.
Article in English | MEDLINE | ID: mdl-38465919

ABSTRACT

Since the introduction of Invisalign by Align Technology, Inc. in 1999, questions and debates have persisted regarding the precision of Invisalign (clear aligner) therapy, particularly when compared to the use of traditional fixed appliances. This becomes particularly significant in cases involving anteroposterior, vertical, and transverse corrections, where precise comparisons are of paramount importance. To address these inquiries, this study introduces a meticulously devised protocol, placing a primary emphasis on digitally superimposing the movement of maxillary posterior teeth to facilitate accurate analysis. The sample included 25 patients who had completed their first series of Invisalign (clear) aligners. Four maxillary digital models (pre-treatment, post-treatment, ClinCheck-initial, and final models) were digitally superimposed using the palate rugae and dentitions as stable references. A software combination was used for model superimposition and tooth segmentation. Transformation matrices then expressed the differences between the achieved and predicted tooth positions. Thresholds for clinically relevant differences were at ±0.25 mm for linear displacement and ±2° for rotation. Differences were assessed using Hotelling's T-squared tests with Bonferroni correction. The mean differences in rotation (2.036° ± 4.217°) and torque (-2.913° ± 3.263°) were significant statistically and clinically, with p-values of 0.023 and 0.0003 respectively. De-rotation of premolars and torque control for all posterior teeth were less predictable. All mean differences for the linear measurements were statistically and clinically insignificant, except that the first molars seemed slightly (0.256 mm) more intruded than their predicted position. The clear aligner system appears to meet its prediction for most translational tooth movements and mesial-distal tipping in maxillary posterior teeth for non-extraction cases with mild to moderate malocclusions.


Subject(s)
Malocclusion , Orthodontic Appliance Design , Humans , Malocclusion/therapy , Bicuspid , Molar , Palate
3.
Front Oncol ; 14: 1295847, 2024.
Article in English | MEDLINE | ID: mdl-38450193

ABSTRACT

Background: Lung cancer is currently the most fatal form of cancer worldwide, ranking as the fourth most prevalent type in Saudi Arabia, particularly among males. This trend is expected to increase with growing population, lifestyle changes, and aging population. Understanding the awareness of the Saudi population regarding the risk factors and symptoms of lung cancer is necessary to attenuate the predicted increase in cases. Method: A cross-sectional, population-based survey was performed using a previously validated questionnaire (Lung CAM). Multiple linear regression analysis was used to assess variables associated with deficiency in knowledge and awareness of risk factors and symptoms of lung cancer. Results: Majority of the 15,099 respondents were male (65%), aged between 18 and 30 years (53%), 50% of which were educated up to a bachelor's degree level. Overall awareness of lung cancer signs and symptoms was 53%, with painful cough and coughing up blood being the best-known symptoms. Conversely, persistent shoulder pain (44%) and clubbing fingers (47%) were the least known lung cancer symptoms. Also, 60% of the respondents showed low confidence in identifying the signs and symptoms of lung cancer. The overall awareness of the risk factors for lung cancer development was 74%, with first-hand (74%) and second-hand (68%) smoking being the most known risk factors. However, only ≤ 62% know the other non-smoking risk factors. Awareness of the risk factors and symptoms of lung cancer depended on age, gender, education, marital and employment status (p < 0.001). Conclusion: Public awareness of the risk factors and symptoms of lung cancer in Saudi Arabia is inadequate and heavily dependent on education and socio-economic status. Awareness can be improved through campaigns to raise awareness about other lesser-known lung cancer risk factors and symptoms.

4.
Sci Rep ; 13(1): 4084, 2023 03 11.
Article in English | MEDLINE | ID: mdl-36906671

ABSTRACT

The purpose of this study was to demonstrate a new method for quantifying the difference between predicted and achieved tooth movement with Invisalign using stable three-dimensional (3D) mandibular landmarks and dental superimposition. Cone-beam computed tomography (CBCT) scans before (T1) and after (T2) the first series of aligners, their corresponding digital models (ClinCheck initial of the first series as T1 and ClinCheck initial of the refinement series as T2), and the ClinCheck final model of the first series as the predicted were obtained from 5 patients treated with non-extraction Invisalign therapy. After segmentation of the mandible and its dentition, T1 and T2 CBCTs were superimposed on stable anatomic structures (Pogonion and bilateral mental foramen) along with the pre-registered ClinCheck models. The 3D prediction differences between the predicted and achieved tooth position for 70 teeth with four types (incisor, canine, premolar and molar) were measured using a combination of software. The method employed in this study was tested to be reliable and repeatable with a very high intraclass correlation coefficient (ICC) for both intra- and inter-examiner reliability. Premolar Phi (rotation), Incisor Psi (mesiodistal angulation), and Molar Y (mesiodistal translation) showed a significant prediction difference (P < 0.05), which is also clinically relevant. The method involving CBCT and individual crown superimposition to measure the 3D positional changes in the mandibular dentition is a robust and novel one. While, our finding in terms of the predictability of Invisalign treatment in the mandibular dentition mainly served as a crude, cursory examination, which warrants further and more rigorous investigations. With this novel methodology, it is possible to measure any amount of 3D tooth position difference in the mandibular dentition either between the simulated and the actual or with treatment and/or growth. Deliberate use of overcorrection of which specific type of tooth movement with clear aligner treatment and to what extent, might be possible with future studies.


Subject(s)
Malocclusion , Orthodontic Appliances, Removable , Spiral Cone-Beam Computed Tomography , Humans , Reproducibility of Results , Malocclusion/therapy , Tooth Movement Techniques/methods , Incisor , Crowns , Mandible
5.
kanem j. med. sci ; 16(1): 124-131, 2023. tables
Article in English | AIM (Africa) | ID: biblio-1427382

ABSTRACT

Background: Coronavirus (COVID-19) which emerged from Wuhan, Hubei province, China has gained tremendous attention. It has caused huge morbidity and mortality as well as a visible psychological burden on communities across the globe. Knowledge, fear, and willingness to accept COVID-19 Vaccine are reported to be serious factors in the fight against the disease in many communities for which Jere LGA, Maiduguri, Borno State, may not be an exception. Objectives: To determine the Knowledge, fear, and willingness to accept the COVID-19 Vaccine among the residents of Jere LGA, Maiduguri, Borno State, Nigeria. Methodology:Adescriptive cross-sectional study design was adopted for this study. Atotal of 384 questionnaires were administered in this study. However, only 367 questionnaires were retrieved for analysis. The sampling technique adopted for this study was multistate sampling techniques. Results: The findings of the study revealed that the majority (67.8%) of the respondents had poor knowledge of the COVID-19 vaccine. On the question of COVID-19 fear, 50.1% had moderate fear. Regarding the vaccination status of the respondents, 93.5% did not receive the COVID-19 vaccine jab and 6.5% did receive the vaccine as of the time of this study. Of the 367 respondents, 78.2% were unwilling to accept the COVID-19 vaccine, if made available to them. Conclusions: The study concluded that there is poor knowledge, and moderate fear and the majority of respondents were unwilling to receive or accept the COVID-19 vaccine in the study area. Therefore, this study recommends a comprehensive awareness campaign on the importance of the COVID-19 vaccine at the community level.


Subject(s)
Humans , Cross-Sectional Studies , Fear , COVID-19 Vaccines , Coronavirus , Knowledge
6.
Saudi Med J ; 43(12): 1324-1332, 2022 Dec.
Article in English | MEDLINE | ID: mdl-36517066

ABSTRACT

OBJECTIVES: To identify potential compounds by seeking the knowledge of molecular interactions between human immunodeficiency virus (HIV) glycoprotein (gp) 120 protein and anti-HIV drug (BMS-488043). METHODS: This study is a computational structure-based drug design study, carried out at University of Taif, Saudi Arabia and African Genome Centre (AGC), Mohammed VI Polytechnic University, Benguerir, Morocco from January 2021 to March 2022. Initially, using the docked structure of gp120 with BMS-488043, a structure-based pharmacophore model was created. The generated model was utilized for virtual screening of the ZINC and ChemBridge database in order to identify hit compounds. To further assess the time-dependent stability of the selected complexes, computer simulation was performed. RESULTS: From pharmacophore-based screening, 356 hits were obtained from both the database. The docking studies of the retrieved hit compounds reveal that all the compounds fit into the binding site of gp120. However, based on the significant interactions with the crucial residues and docking scores four compounds were suggested as potential hits. MD simulation of ChemBridge14695864 and ZINC06893293 in complex with gp120 suggested that both compounds significantly stabilized the receptor. CONCLUSION: These findings could aid in the design of effective drugs against HIV by inhibiting the interaction between gp120 and CD4.


Subject(s)
HIV-1 , Molecular Dynamics Simulation , Humans , Molecular Docking Simulation , Ligands , Pharmacophore , Lead
7.
Clin Lab ; 68(11)2022 Nov 01.
Article in English | MEDLINE | ID: mdl-36378000

ABSTRACT

BACKGROUND: This study evaluates the seroprevalence of immunoglobulin M (IgM) and G (IgG) antibodies against SARS-CoV-2 after two doses of Pfizer-BioNTech COVID-19 vaccination from women with breast cancer in Jazan city Kingdom of Saudi Arabia, antibody detections were performed one month and three months after the administration of the second dose. METHODS: Overall, 103 breast cancer patients were included. Individuals who had had two doses of Pfizer-BioNTech vaccine, patients who were earlier diagnosed with COVID-19 infection, had not finalized immunization plan, or who received the second dose recently were excluded from the study. The antibodies detection test was run according to the manufacturer's directions of Viva Diag™ SARS-CoV-2 IgM/IgG Rapid Test (COVID-19 IgM/IgG Rapid Test). RESULTS: This study included 62 (60.2%) and 41 (39.8%) patients with invasive ductal carcinoma and invasive lobular carcinoma, respectively. The age, median and interquartile range (IQR) was 54.0 (26) years. Regarding reactivity of antibodies, after one month IgM antibody showed 64 (62.1%) positive and 39 (37.9%) negative while IgG antibody showed positive results in all patients. After three months IgM antibody showed 44 (42.7%) positive and 59 (57.3%) negative, while IgG showed 87 (84.5%) positive and 16 (15.5%) negative. There were significant differences in the IgM and IgG seropositivity. There were 19.3% patients with ductal carcinoma who were positive and then turned negative versus 17.7% who were positive and then turned negative, respectively (p < 0.001). There were significant differences in IgM antibody positivity among different age groups. CONCLUSIONS: Our results recommend the importance of screening for an antibody response for breast cancer patient after immunization in order to reveal persons who need early and late extra enhancing vaccine dose. Upcoming studies recommended to estimate different methods that raise cancer patients' immune response.


Subject(s)
Breast Neoplasms , COVID-19 , Carcinoma, Ductal , Humans , Female , Middle Aged , SARS-CoV-2 , Immunoglobulin M , Seroepidemiologic Studies , COVID-19/epidemiology , COVID-19/prevention & control , BNT162 Vaccine , COVID-19 Vaccines , Antibodies, Viral , Immunoglobulin G
8.
In Vivo ; 36(5): 2414-2421, 2022.
Article in English | MEDLINE | ID: mdl-36099148

ABSTRACT

BACKGROUND/AIM: Cervical cancer remains a major public health concern. The ratio of CD4+:CD8+ T-cells is used to evaluate the immune system function. This study aimed to explore the CD4+:CD8+ T-cell ratio in relation to the glycemic status, inflammatory markers, vitamin D, and vitamin B12 in patients with early diagnosed cervical cancer. PATIENTS AND METHODS: This is a cross-sectional study. Blood samples were collected for flow cytometry analysis. Information regarding Papanicolaou (Pap) smears and colposcopy investigations were collected from 152 women with type 2 diabetes admitted to East Jeddah Hospital, Jeddah, Saudi Arabia, between January 2018 and January 2021. RESULTS: Patients with early cervical carcinoma and a higher CD4+:CD8+ ratio (>1.2) had a higher C-reactive protein (CRP) level than those with a lower CD4+:CD8+ ratio (Mean±SD=13.75±13.3 vs. 10.85±8.1; p-value=0.034). Patients with early cervical carcinoma, diabetes, and higher CD4+:CD8+ ratio (>1.2) had a higher blood HbA1c percent than those with a lower CD4+:CD8+ ratio. CONCLUSION: A high CD4+:CD8+ T-cells ratio was associated with an increased HbA1c% and CRP levels in women with diabetes diagnosed with early cervical carcinoma, which can induce inflammation in early diagnosed patients with cervical cancer.


Subject(s)
Diabetes Mellitus, Type 2 , Uterine Cervical Neoplasms , Biomarkers , CD4-Positive T-Lymphocytes/pathology , CD8-Positive T-Lymphocytes/pathology , Cross-Sectional Studies , Diabetes Mellitus, Type 2/pathology , Female , Glycated Hemoglobin , Humans , Uterine Cervical Neoplasms/diagnosis , Uterine Cervical Neoplasms/pathology
9.
Biomed Res Int ; 2021: 1622270, 2021.
Article in English | MEDLINE | ID: mdl-34409099

ABSTRACT

This study investigates the antioxidant activities of lipid, protein, and carbohydrate extracts from the marine mollusk Perna canaliculus. Lipids were extracted using acetone, which was followed by protein extraction using the broad-spectrum enzyme Alcalase and then carbohydrate extraction using cetylpyridinium chloride. Eighty white BALB/c mice were divided into eight groups according to the administered extracts. Groups 1 and 5 were the control and toxin control groups, respectively. Groups 2, 3, and 4 were administered lipid, protein, and carbohydrate extracts, respectively. The other groups were administered P. canaliculus extracts as well as gentamicin and acetaminophen, known as ethanolic extracts, derived from Nerium oleander to induce oxidation stress. All groups showed significant improvements in body weight (p < 0.05). The lipid extract group showed a significant decrease in low-density lipoprotein cholesterol (p < 0.05) and a significant increase in high-density lipoprotein cholesterol (p < 0.05). After the toxin injection, all groups treated with P. canaliculus extracts showed increased antioxidant effects on hepatocytes (p < 0.05). The lipid extracts induced antioxidant effects to protect the kidney by increasing lipid peroxidation (p < 0.05) and catalase activities (p < 0.05). Also, protein extracts showed antioxidant effects by increasing glutathione and catalase levels significantly (p < 0.005). In conclusion, P. canaliculus extracts, especially lipids and proteins, have potent antioxidant activities that protect vital organs from oxidation stress.


Subject(s)
Antioxidants/administration & dosage , Carbohydrates/administration & dosage , Lipids/administration & dosage , Perna/chemistry , Proteins/administration & dosage , Animals , Antioxidants/isolation & purification , Antioxidants/pharmacology , Biological Products/isolation & purification , Carbohydrates/isolation & purification , Carbohydrates/pharmacology , Catalase/metabolism , Ethanol/administration & dosage , Ethanol/pharmacology , Glutathione/metabolism , Lipid Peroxidation/drug effects , Lipids/isolation & purification , Lipids/pharmacology , Male , Mice , Mice, Inbred BALB C , Models, Animal , Nerium/chemistry , Oxidative Stress/drug effects , Proteins/isolation & purification , Proteins/pharmacology
10.
J Food Biochem ; 45(9): e13865, 2021 09.
Article in English | MEDLINE | ID: mdl-34263474

ABSTRACT

In the past decade, the use of marine mussels as seafood is being more popular. They considered being a rich source of various nutritional bioactive compounds that aroused the scientific community's interest. This study investigated the antioxidant and the antithrombotic consequences on Sprague-Dawley male rats after adding dried New Zealand mussel Perna canaliculus in their diet. The biochemical, hematological and histopathological changes were also observed. Forty rats were divided into four groups according to the amount of dried mussels in their diet, in addition to a control group that consumed a basal diet only. Group 1 consumed 25% dried mussels in its basal diet; Group 2 consumed 35% dried mussels in its basal diet, and Group 3 was consumed 45% dried mussels in its basal diet. The biochemical parameters showed improvements in liver function. Interestingly, the lipid profile decreased, especially the low-density lipoprotein cholesterol (LDL-C) levels which were reduced significantly in Group 3 (p < .01). These observations were accompanied by a decrease in iron levels significantly as the amount of dried mussels increased (p < .01). Furthermore, the noticed changes in the hematological profile prove that there is an increase in antithrombotic activity. Dried mussels had potent antioxidant effects in the liver as shown by increased lipid peroxide (p < .05), reduced glutathione (p < .05), and glutathione peroxidase (GSH-Px; p < .05). Additionally, antioxidant activity in the kidney was shown to increase through GSH-Px activity (p < .01). In conclusion, these results indicate that consuming dried mussels resulted in improved biochemical and antioxidants activities and could be used as an antithrombotic agent.


Subject(s)
Perna , Animals , Antioxidants/pharmacology , Fibrinolytic Agents/pharmacology , Male , Rats , Rats, Sprague-Dawley , Seafood
11.
Cureus ; 12(5): e8304, 2020 May 26.
Article in English | MEDLINE | ID: mdl-32601576

ABSTRACT

Objectives We investigated the relationship between acromial shape, classified as Type I-IV by magnetic resonance imaging, and the occurrence and characteristics of rotator cuff tears (RCTs). Methods This retrospective cohort study included 89 patients aged 25 - 60 years who underwent RCT surgeries in the Orthopedic Department at King Abdulaziz University Hospital (KAUH) from January 2014 to April 2019. We collected imaging findings from the KAUH record system, which were then entered into a Google form (Google, Inc., Mountain View, CA) and exported to Microsoft Excel 2016 (Microsoft® Corp., Redmond, WA). Correlations between variables were assessed using Chi-squared tests. Results The supraspinatus muscle in both men and women was most commonly affected by RCTs, accounting for 73.6% of all tears. Subscapularis was the next most commonly injured muscle of the rotator cuff (15.1%), followed by the infraspinatus muscle (11.3%). The majority of supraspinatus, infraspinatus, and subscapularis tears (69.2%, 66.7%, and 56.3%, respectively) were associated with flat acromia. In all cases, tears in association with flat acromia were more prevalent among women (supraspinatus: 51.3% in women, 17.9% in men, p = 0.030; infraspinatus: 50% in women, 16.7% in men, p = 0.292; subscapularis: 43.8% in women, 12.5% in men, p = 0.054). Conclusions No correlation exists between acromial shape and sex, regardless of the specific muscle injured. However, supraspinatus injury, acromial shape, and sex are significantly related; right-side partial tear injuries occur more frequently among women aged ≥ 50 years with flat acromia than other RCTs.

12.
Indian J Med Microbiol ; 38(1): 94-100, 2020.
Article in English | MEDLINE | ID: mdl-32719215

ABSTRACT

Purpose: Helicobacter pylori is one of the most prevalent human pathogens worldwide. However, the outcomes of H. pylori infection are markedly variable from asymptomatic mild lesion to malignant transformation. Many factors are suggested to influence these infection outcomes, including host immunity and genetic susceptibility. Toll-like receptors (TLRs) can recognise different microbial components and play an essential role in the mucosal immune response against H. pylori infection. Materials and Methods: The association between the common single nucleotide polymorphisms (SNPs) in the genes of TLR2, 4, 9 and 10 and H. pylori-related gastric diseases were investigated by molecular methods after the confirmation of H. pylori infection. The study included 210 patients in three groups; chronic gastritis (n = 90), peptic ulcer disease (PUD) (n = 75) and gastric carcinoma (n = 45). Results: The results showed a significant association between TLR4 SNPs (rs 4986790 and rs 4986791) and the presence of H. pylori infection, especially in chronic gastritis patient group. Furthermore, TLR9-rs352140 TT genotype was more prevalent among chronic gastritis patient group. TLR10-rs 10004195 TT genotype was found to be less prevalent among H. pylori-related chronic gastritis and PUD and was suspected to have a protective effect. TLR2 SNPs (rs3804099 and rs3804100) showed no significant statistical difference between H. pylori-infected patients and the controls. Conclusion: TLR genes polymorphisms may play a role in H. pylori infection susceptibility and may influence its outcomes; however, the ethnic and other factors may modify this effect.


Subject(s)
Genetic Predisposition to Disease , Helicobacter Infections/genetics , Stomach Diseases/genetics , Stomach Diseases/microbiology , Toll-Like Receptors/genetics , Adult , Biopsy , Case-Control Studies , Female , Genotyping Techniques , Helicobacter Infections/epidemiology , Helicobacter pylori/isolation & purification , Humans , Male , Middle Aged , Polymorphism, Single Nucleotide , Saudi Arabia/epidemiology , Toll-Like Receptor 10/genetics , Toll-Like Receptor 2/genetics , Toll-Like Receptor 4/genetics , Toll-Like Receptor 9/genetics , Young Adult
13.
IUBMB Life ; 72(10): 2121-2132, 2020 10.
Article in English | MEDLINE | ID: mdl-32710811

ABSTRACT

Sepsis results from a major systemic inflammatory response and can induce disorders in multiple organs. The present study evaluated the potential protective effects of oleuropein (OLE) against hyperinflammatory responses during lipopolysaccharide (LPS)-induced sepsis in mice. Sixty male Balb/c mice were randomly categorized into five groups of 12 animals each: control, intraperitoneally injected with OLE (50 mg/kg), injected with LPS (10 mg/kg, intraperitoneal), and two groups administered OLE (25 and 50 mg/kg) for 3 days prior to LPS injection. Twenty-four hours after lipopolysaccharide injection, the animals were sacrificed. Serum, liver, and kidney tissue samples were collected for biochemical analyses, histopathological examinations, and investigation of inflammation-related gene expression. OLE pretreatment significantly reduced liver damage parameters (alanine aminotransferase, aspartate aminotransferase, lactate dehydrogenase) and kidney damage parameters (blood urea nitrogen, creatinine, and kidney injury molecule-1) in the septic mice. OLE pretreatment ameliorated LPS-induced liver and kidney histological changes. OLE significantly mitigated the increased levels of malondialdehyde in the liver and kidneys and reduced levels of reduced glutathione induced by LPS. LPS injection also resulted in increased expression of the proinflammatory cytokines (TNF-α, IL-1ß, and IL-6) and inflammation-related genes (Nos2, Hmgb1, Mpo, Cd46, Map2k4, and Map2k7) in the hepatic and renal tissues. OLE reduced these expressions to ameliorate the inflammatory response. Moreover, OLE pretreatment enhanced the survival rate of septic mice. In conclusion, OLE alleviated the inflammatory response to protect against LPS-induced sepsis in mice.


Subject(s)
Iridoid Glucosides/pharmacology , Kidney/drug effects , Liver/drug effects , Protective Agents/pharmacology , Sepsis/prevention & control , Animals , Cytokines/metabolism , Gene Expression Regulation/drug effects , Kidney/physiopathology , Kidney Function Tests , Lipopolysaccharides/toxicity , Liver/physiopathology , Liver Function Tests , Male , Mice, Inbred BALB C , Oxidative Stress/drug effects , Sepsis/chemically induced , Sepsis/mortality , Sepsis/physiopathology , Survival Rate
14.
EMBO Mol Med ; 6(2): 183-93, 2014 02.
Article in English | MEDLINE | ID: mdl-24413189

ABSTRACT

Disorders of the mitochondrial genome cause a wide spectrum of disease, these present mainly as neurological and/or muscle related pathologies. Due to the intractability of the human mitochondrial genome there are currently no effective treatments for these disorders. The majority of the pathogenic mutations lie in the genes encoding mitochondrial tRNAs. Consequently, the biochemical deficiency is due to mitochondrial protein synthesis defects, which manifest as aberrant cellular respiration and ATP synthesis. It has previously been reported that overexpression of mitochondrial aminoacyl tRNA synthetases has been effective, in cell lines, at partially suppressing the defects resulting from mutations in their cognate mt-tRNAs. We now show that leucyl tRNA synthetase is able to partially rescue defects caused by mutations in non-cognate mt-tRNAs. Further, a C terminal peptide alone can enter mitochondria and interact with the same spectrum of mt-tRNAs as the entire synthetase, in intact cells. These data support the possibility that a small peptide could correct at least the biochemical defect associated with many mt-tRNA mutations, inferring a novel therapy for these disorders.


Subject(s)
Amino Acyl-tRNA Synthetases/metabolism , Mitochondria/genetics , Mutation/genetics , RNA, Transfer, Leu/genetics , Suppression, Genetic , Amino Acyl-tRNA Synthetases/chemistry , Cell Proliferation , Humans , Mitochondria/enzymology , Oxidative Phosphorylation , Phenotype , Protein Binding , Protein Structure, Tertiary
15.
Bone ; 47(4): 804-14, 2010 Oct.
Article in English | MEDLINE | ID: mdl-20659600

ABSTRACT

Biochemical bone turnover markers (BTMs) provide important information on the diagnosis, therapy and monitoring of metabolic bone diseases including osteoporosis. One goal of antiresorptive therapy in women is to decrease biochemical BTMs to the lower half of reference intervals for healthy pre-menopausal counterparts, using newly developed automated assays of such markers. The main objectives of the present study were to: (1) establish reference interval values for the following biochemical BTMs: serum osteocalcine (s-OC), bone alkaline phosphatase (s-bone ALP), procollagen type 1 N-terminal propeptide (s-PINP), crosslinked C-terminal telopeptide of Type 1 collagen (s-CTX), tartarate-resistant acid phosphatase isoform 5b (s-TRACP-5b) and urinary: CTX (u-CTX), N-telopeptides of type 1 collagen (u-NTX), pyridinoline (u-PYD) and deoxypyridinoline (u-DPD) in randomly selected Saudi healthy pre-menopausal women; (2) study the changes in biochemical BTMs in relation to age in pre- and post-menopausal women and the factors reported to influence bone turnover and (3) determine the effect of menopausal status on BTMs. A total of 2125 women were studied [including (n=1557) pre-, and (n=568) post-menopausal women, respectively, aged 20-79 years]. A total of 765 healthy pre-menopausal women (aged 35-45 years) were used to establish reference intervals for biochemical BTMs. All women studied were medically examined and had their bone mineral density (BMD) values obtained for the lumbar spine (L(1)-L(4)) and femoral neck according to detailed inclusion criteria. In all women, values of biochemical BTMs, decreased with increasing age up to the age of 45 years, increased steeply among women in their 50s and remained increased in post-menopausal women. Significant increases were evident in all biochemical BTMs in post-menopausal women with >5 years since menopause with the exception of s-OC, u-DPD, and u-PYD. Using stepwise multiple linear regression analysis, several variables were identified (depending on the BTM) as determinants of BTMs including age, BMI, parity, FSH, LH, PTH, s-Ca, s-Mg, s-PO(4) and 25(OH)D. In the reference intervals group, there are no significant correlations between any of the biochemical BTMs and age of menarche, day of menstrual cycle, physical activity, total daily dietary calcium and caffeine intakes and parity. It is recommended that the age range 35-45 years should be used when establishing biochemical BTMs reference intervals in Saudi Arabian pre-menopausal women.


Subject(s)
Biomarkers/metabolism , Bone Remodeling/physiology , Adult , Aged , Aging/physiology , Analysis of Variance , Anthropometry , Bone Density/physiology , Confidence Intervals , Cross-Sectional Studies , Female , Humans , Menopause/physiology , Middle Aged , Multivariate Analysis , Parathyroid Hormone/metabolism , Reference Values , Regression Analysis , Saudi Arabia , Young Adult
16.
Saudi Med J ; 23(10): 1222-6, 2002 Oct.
Article in English | MEDLINE | ID: mdl-12436126

ABSTRACT

OBJECTIVE: The present study was conducted to estimate vaccination coverage against hepatitis B virus and the perceptions of 1198 medical sciences students in Sana'a City, Yemen. METHODS: Only those who practice clinical training or are in contact with body fluids were included. The students were enrolled in the Faculty of Medicine and Health Sciences, Sana'a University, Republic of Yemen. Data was collected from 1999-2000. Arabic pre-tested questionnaire forms were completed by 840 students at a response rate of 70.6%. RESULTS: The study revealed a reported vaccination rate of 29.5%. The rate among Faculty of Medicine and Health Sciences students was 32.3%, whereas only 21.3% among the students of High Institute of Health Sciences. Students of dentistry attained the highest rate of vaccination (38.8%), while nursing students of the High Institute of Health Sciences achieved the lowest rate (17.1%). Rate of vaccination (46.6%) among female students was significantly higher than male students (22.3%) with a P- value of 0.0001. Medical assistants of the High Institute of Health Sciences scored the best (56%) in terms of knowledge, medical laboratory sciences students achieved the highest (43.6%) in attitude and dentistry students had the highest scores (35.5%) in practices. The mean knowledge of females and males was comparable, however, females achieved higher attitudes and practices. Final stage students attained better attitude scores than the pre-final and intermediate students. CONCLUSION: Vaccination coverage of medical sciences students in Sana'a City, Yemen is low. Knowledge of medical assistants is the best, attitude of medical laboratory sciences students and practices of dental students is the highest. Attitudes and practices of female students are better than that of males.


Subject(s)
Health Knowledge, Attitudes, Practice , Hepatitis B Vaccines , Students, Health Occupations , Vaccination , Humans , Male , Vaccination/statistics & numerical data , Yemen
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