Endothelial Nitric Oxide Synthase Gene Polymorphisms Increase Risk of Deep Vein Thrombosis by Altering Homocysteine Levels.

BACKGROUND: Deep Vein Thrombosis (DVT) is a multicausal disease involving both acquired as well as genetic factors. Nitric oxide is an influential endogenous factor having its role in the development of deep vein thrombosis. It maintains the vascular integrity and any alterations in its levels may lead to a thrombotic event. It may also modulate homocysteine metabolism to cause hyperhomocysteinemia, which is a prominent risk factor for thrombosis. The objective of the study was to study if endothelial nitric oxide gene polymorphisms, 894G/T, and 2479G/A alter the plasma nitric oxide and homocysteine levels which may eventually increase the risk of deep vein thrombosis. METHODS: One hundred Doppler ultrasonography and computerized tomography confirmed (for cerebral venous thrombosis), non-related DVT patients (M:F = 58:42; age range = 18 to 61 years) served as the study population. Two hundred hospital staff and their relatives or unrelated attendants of the patients served as the controls. Nitric oxide levels were determined by measuring its metabolites (NOx), and EIA was used to measure homocysteine levels. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was used for detecting the eNOS polymorphisms 894G/T and 2479G/A. RESULTS: In total, DVT subjects have 25% higher plasma levels of homocysteine and 37% lower levels of NOx in their circulation when compared to controls. In tertile analysis of nitric oxide and homocysteine levels, 894G/T and 2479G/A polymorphisms were associated with plasma nitric oxide and homocysteine levels. The increased risk of deep vein thrombosis was associated with endothelial nitric oxide gene polymorphisms and nitric oxide levels, but homocysteine levels were not a risk for deep vein thrombosis. CONCLUSION: The present study demonstrates that 894G/T and 2479G/A polymorphisms interact with lower levels of nitric oxide and higher levels of homocysteine that may possess the risk of deep vein thrombosis.

Iron Deficiency Anemia as a Factor in Male Infertility: Awareness in Health College Students in the Jazan Region of Saudi Arabia.

Male contribution towards couple infertility is increasing but is less discussed. We aimed to assess the knowledge about iron deficiency anemia (IDA) as a contributor to male infertility in students at health colleges of Jazan University. A multicentric, cross-sectional survey included 910 participants and 768 participants qualified as per our inclusion criteria. The questions were categorized as: Model 1-knowledge about IDA-induced male infertility; Model 2-knowledge about IDA. The average knowledge of IDA causing male infertility is very low among students. The 18-20 years age group had a lesser score for either knowledge of IDA (M2; p-value = 0.047) or total (p-value < 0.0001) compared to the older group. In addition, female students were significantly more likely to be better in achieving higher total scores (p-value = 0.023) as well as M2 scores (p-value < 0.0001) when compared to the respective male category. On the other hand, males were significantly better in scoring for M1 (p-value = 0.004) compared to females. Awareness about iron deficiency anemia as a factor in male infertility may reduce the infertility burden, arising from a preventable factor, in the Jazan region.

Routine laboratory parameters predict serious outcome as well as length of hospital stay in COVID-19.

OBJECTIVES: To validate C-reactive protein (CRP), red cell distribution width (RDW), and neutrophil lymphocyte ratio (NLR) for both serious outcomes and length of hospital stay (LOS) among hospitalized coronavirus disease-19 (COVID-19) patients. METHODS: Laboratory data of adult COVID-19 patients (n=74) was collected in this retrospective cohort. Logistic regression was employed for risk factor evaluation and receiver operating curve was used for comparison of these risk factors for the prediction of serious outcome. Multiple regression was applied to determine the association between routine analytes and LOS. RESULTS: Higher levels of CRP (3 times), white blood cells (20%), and neutrophil counts (40%) were seen in the serious category. Odds ratio for CRP for the serious outcome was 1.052 (p=0.007) and RDW for the serious outcome was 1.218 (p=0.040) in unadjusted model and odds ratio for CRP for the serious outcome was 1.048 (p=0.024) and for RDW 1.286 (p=0.023) in adjusted model. In a multivariate regression analysis for the LOS of the unadjusted models consisting of NLR, monocyte lymphocyte ratio (MLR) and platelet lymphocyte ratio (PLR), the beta coefficients (BC) for the CRP were 0.006 (NLR), 0.005 (MLR) and 0.006 (PLR), whereas -0.029 (NLR), -0.034 (MLR) and -0.027 (PLR) were BCs for mean corpuscular hemoglobin concentration (MCHC). Additionally, in adjusted models, the BCs for MCHC were -0.044 (NLR), -0.047 (MLR) and -0.043 (PLR). However, the CRP was consistent with 0.004 (BC) in all models. CONCLUSION: We observed that CRP is a better predictor than RDW and NLR for serious outcome among COVID-19 patients. Besides, CRP was positively, whereas MCHC was negatively associated with LOS.

Inhibiting Effect of Zinc Oxide Nanoparticles on Advanced Glycation Products and Oxidative Modifications: a Potential Tool to Counteract Oxidative Stress in Neurodegenerative Diseases.

Advanced glycation end products (AGEs) are implicated in several central nervous system (CNS) pathologies including Alzheimer and Parkinson's diseases. In the face-off of AGE menace, we have attempted to investigate the zinc oxide nanoparticle (ZnONP) role in inhibition of AGE formation. Synthesized ZnONPs were used to investigate the inhibitory effects on AGE formation. The inhibitory effects of ZnONPs on AGE formation were determined by biophysical immunological and biochemical techniques. The results showed that ZnONP is a potential anti-glycating agent inhibiting AGE formation as well as protecting the protein structure from change. Therefore, our findings suggest ZnONPs may be used as a therapeutic in resolving the AGE role in CNS-related complications.

Lycopene amends LPS induced oxidative stress and hypertriglyceridemia via modulating PCSK-9 expression and Apo-CIII mediated lipoprotein lipase activity.

This study was undertaken to uncover the regulatory role of lycopene in targeting lipopolysaccharide (LPS) induced oxidative stress and inflammatory cascades and subsequent regulation of proprotein convertase subtilisin/kexin type-9 (PCSK-9) expression via sterol regulatory element binding protein-2 (SREBP-2) and hepatocyte nuclear factor-1α (HNF-1α). Further, protein-protein interaction (PPI) studies for Lycopene-Apo-CIII complex against lipoprotein lipase (LPL) were also performed to assess its regulatory role behind the enhanced circulatory TG/TRLs clearance. Lycopene treatment down-regulated hepatocyte PCSK-9 expression via down-regulation of HNF-1α, whereas, LDL-receptor (LDL-R) was up-regulated by subsequent up-regulation of SREBP-2. PPI studies showed that lycopene diminishes the affinity of Apo-CIII to complex with LPL (ΔG: -917.1 Kcal/mol) resulting in increased LPL functionality and TRLs clearance. Moreover, lycopene also ameliorated LPS stimulated oxidative-stress via enhanced total antioxidant and HDL associated PON-1 activity in addition to down-regulate the expression and plasma level of inflammatory mediators. Based on above findings, we concluded that lycopene exhibits dual role in targeting LPS induced oxidative stress and hypertriglyceridemia via down-regulation of PCSK-9, making greater no. of surface LDL-R available for LPS processing and clearance, as well as increased LPL activity through inhibition of Apo-CIII.

Potential role of lycopene in targeting proprotein convertase subtilisin/kexin type-9 to combat hypercholesterolemia.

Proprotein convertase subtilisin/kexin type 9 (PCSK-9) is a serine protease of the proprotien convertase (PC) family that has profound effects on plasma low density lipoprotein cholesterol (LDL-C) levels, the major risk factor for coronary heart disease (CHD), through its ability to mediate LDL receptor (LDL-R) protein degradation and reduced recycling to the surface of hepatocytes. Thus, the current study was premeditated not only to evaluate the role of lycopene in targeting the inhibition of PCSK-9 via modulation of genes involved in cholesterol homeostasis in HFD rats but also to examine a correlation between HFD induced inflammatory cascades and subsequent regulation of PCSK-9 expression. Besides the effect of lycopene on hepatic PCSK-9 gene expression, PPI studies for PCSK-9-Lycopene complex and EGF-A of LDL-R were also performed via molecular informatics approach to assess the dual mode of action of lycopene in LDL-R recycling and increased removal of circulatory LDL-C. We for the first time deciphered that lycopene treatment significantly down-regulates the expression of hepatic PCSK-9 and HMGR, whereas, hepatic LDL-R expression was significantly up-regulated. Furthermore, lycopene ameliorated inflammation stimulated expression of PCSK-9 via suppressing the expression of inflammatory markers. The results from our molecular informatics studies confirmed that lycopene, while occupying the active site of PCSK-9 crystal structure, reduces the affinity of PCSK-9 to complex with EGF-A of LDL-R, whereas, atorvastatin makes PCSK-9-EGF-A complex formation more feasible than both of PCSK-9-EGF-A alone and Lycopene-PCSK-9-EGF-A complex. Based on above results, it can be concluded that lycopene exhibits potent hypolipidemic activities via molecular mechanisms that are either identical (HMGR inhibition) or distinct from that of statins (down-regulation of PCSK-9 mRNA synthesis). To the best of our knowledge, this is the first report that lycopene has this specific biological property. Being a natural, safer and alternative therapeutic agent, lycopene could be used as a complete regulator of cholesterol homeostasis and ASCVD.

ROLE OF SURGICAL APPROACHES INFLUENCING TUMOUR RECURRENCE IN NASOPHARYNGEAL ANGIOFIBROMA.

BACKGROUND: Juvenile nasopharyngeal angiofibroma (JNA) is an uncommon tumour constituting less than 1% of all head & neck tumours. This tumour has an aggressive local behaviour if left untreated. Surgery is the mainstay of treatment with no common consensus on a single approach. Tumour stage and surgical approaches are the major determinants of outcome. The objective of this study was to evaluate the influence of surgical approaches on tumour recurrence in patients with nasopharyngeal angiofibroma. METHODS: This descriptive study was conducted in the Department of ENT and Head and Neck Surgery, PIMS, Islamabad and Ayub Medical Institution, Abbottabad from Jan 2010 to Jan 2014 consisting of 34 diagnosed cases of nasopharyngeal angiofibroma. All patients were treated surgically while radiotherapy was given in a few. All patients were followed up for one year. RESULTS: Among 34 patients, 25 were treated by lateral rhinotomy approach with medial maxillectomy, 5 by mid-facial degloving approach and 3 by transpalatine approach. One patient with cavernous sinus involvement was treated by radiotherapy. Patients were followed up for one year both by clinical examination and imaging if needed. Recurrence was found in 15% (5/33) patients and postop radiotherapy was given to them. CONCLUSION: Lateral rhinotomy approach with medial maxillectomy is highly effective even in advanced stage JNA for complete removal of the disease. Postoperative radiotherapy is an effective adjuvant.

Efficacy of topical clotrimazole in treatment of otomycosis.

BACKGROUND: Otomycosis is a common condition affecting external ear and ears with chronic suppurative otitis media, and has a tendency for recurrence. Objective of this study was to determine the efficacy of topical clotrimazole in the treatment of otomycosis. METHODS: This descriptive study was conducted at the outpatient department of ENT, Ayub Teaching Hospital Abbottabad, from Jul 2012 to Dec 2012. A total of 101 patients were included in this study. The results were compared and analysed regarding age, gender, presenting complaints and efficacy of clotrimazole. RESULTS: A total of 101 patients of otomycosis were included in the study. Male to female ratio was 0.71:1. Patients of 15 years and above were included in the study. Adults were more affected by otomycosis than the younger age group. The efficacy of clotrimazole in treatment of otomycosis was observed in 89 (94.12%) while in 12 (5.88%) patients no efficacy was seen. Age and gender have no role in efficacy of Clotrimazole in treatment of Otomycosis. CONCLUSION: Topical clotrimazole is effective in the treatment of Otomycosis.

Effect of temperature and humidity on epistaxis in Hazara division.

BACKGROUND: Epistaxis is one of the commonest ENT emergencies and is experienced by up to 60% of people in their lifetime, with 6% requiring medical attention. The objective of the study was to determine the frequency of primary epistaxis and its relationship with temperature and relative humidity. METHODS: This cross sectional study included 460 patients with epistaxis attending the ENT Department of Ayub Medical College, Abbottabad. Daily temperature and humidity record was obtained from the department of Hydrology and Meteorology of Hazara Division. The results of four hundred and sixty patients were analyzed for the effect of temperature and humidity on the frequency of epistaxis. Data was analysed using SPSS-11. Pearson's r was calculated to determine correlation between different variables. RESULTS: A total of 460 patients were included, out of which 206 (44.8%) had primary epistaxis. The frequency of primary epistaxis was seen to be higher during the cold period from October to March. Statistical analysis showed good negative correlation between temperature and primary epistaxis (r = -0.948) while average correlation with humidity (r = -0.445). CONCLUSION: The relationship between temperature and primary epistaxis was good while that with relative humidity was average.

Early complications of elective and emergency tracheostomy.

BACKGROUND: Tracheostomy is a life saving procedure when it is performed for an appropriate indication and surgical technique. The aim of this study was to compare the early complications of elective and emergency tracheostomy in our setup. METHODS: This comparative study was conducted at the ENT Department. Hayatabad Medical (Complex (HMC) from March 2009 to March 2010. A total of 100 patients included in this study were divided in to two equal groups, group A undergoing elective tracheostomy and group B undergoing emergency tracheostomy. The results of hundred patients were compared and analysed from stand point of age, sex, disease pattern, operative procedure and postoperative complications associated with tracheostomy. RESULTS: A total of 100 patients were included with age ranging from 17 to 88 years. The average age was 35 years in elective cases and was 32 years in emergency cases. The male to female ratio was 2.9:1 in elective cases and 4.6:1 in emergency cases. The overall complications rates were 38% in elective cases and 56% in emergency cases. CONCLUSION: Early complications of emergency tracheostomy are more common than elective tracheostomy.