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1.
J Interv Cardiol ; 2023: 1117379, 2023.
Article in English | MEDLINE | ID: mdl-36712998

ABSTRACT

Objectives: To determine if radial artery (RA) access compared with femoral artery (FA) access for percutaneous coronary intervention (PCI) is associated with a lower incidence of acute kidney injury (AKI). Background: AKI results in substantial morbidity and cost following PCI. Prior studies comparing the occurrence of AKI associated with radial artery (RA) versus femoral artery (FA) access have mixed results. Methods: Using a large state-wide database, 14,077 patients (8,539 with RA and 5,538 patents with FA access) were retrospectively compared to assess the occurrence of AKI following PCI. To reduce selection bias and balance clinical data across the two groups, a novel machine learning method called a Generalized Boosted Model was conducted on the arterial access site generating a weighted propensity score for each variable. A logistic regression analysis was then performed on the occurrence of AKI following PCI using the weighted propensity scores from the Generalized Boosted Model. Results: As shown in other studies, multiple variables were associated with an increase in AKI after PCI. Only RA access (OR 0.82; 95% CI 0.74-0.91) and male gender (OR 0.80; 95% CI 0.72-0.89) were associated with a lower occurrence of AKI. Based on the calculated Mehran scores, patients were stratified into groups with an increasing risk of AKI. RA access was consistently found to have a lower risk of AKI compared with FA access across these groups of increasing risk. Conclusions: Compared with FA access, RA access is associated with an 18% lower rate of AKI following PCI. This effect was observed among different levels of risk for developing AKI. Although developed from a retrospective analysis, this study supports the use of RA access when technically possible in a diverse group of patients.


Subject(s)
Acute Kidney Injury , Percutaneous Coronary Intervention , Humans , Male , Risk Factors , Retrospective Studies , Radial Artery , Incidence , Percutaneous Coronary Intervention/adverse effects , Percutaneous Coronary Intervention/methods , Treatment Outcome , Femoral Artery , Acute Kidney Injury/epidemiology , Acute Kidney Injury/etiology , Acute Kidney Injury/prevention & control
2.
Afr J Reprod Health ; 27(5): 30-40, 2023 May.
Article in English | MEDLINE | ID: mdl-37584928

ABSTRACT

Polycystic ovarian syndrome manifests acne and alopecia in teenagers and young adult females. To evaluate ovarian morphology and the prevalence of polycystic ovarian morphology (PCOM) in females between the ages of 21 and 45 who are in the reproductive stage and have isolated acne and/or androgenic alopecia. And their association. The present study was done with patients in the age group of 21 to 45 years with acne and/or androgenic alopecia. Modified Ferriman-Gallwey score was used to assess the degree of hirsutism (with score of more or equal to 8 as significant). Grading of acne vulgaris and androgenic alopecia was done by a single observer. Subjects were then evaluated for biochemical investigations of Hormonal assays on day 2 to 7. Transabdominal ultrasonography was performed in the follicular phase to demonstrate the ovarian morphology. In our study isolated androgenic alopecia was present in 28 patients (24.34%). In our study 54 (46.95%) patients out of 115 had combined acne and androgenic alopecia. In our study out of 33 patients with isolated acne 17 (51.5%) had PCO Morphology with grade I, grade II, grade III having prevalence of 46.2%, 53.8% and 57.1% respectively. In our study of the 28 patients with isolated androgenic alopecia 16 (57.1%) had PCOM with grade I, II and III respectively having prevalence of 56.3%, 55.6%, 66.7% with P value of 0.939. Patients with normal ovarian morphology were 12 in number (42.9%). Of the 54 patients with combined acne and androgenic alopecia 32 (59.3%) had PCOM and 22 patients had normal ovarian morphology. Higher overall prevalence was found in patients with combined acne and alopecia (59.3%) than in isolated groups; acne (51.5%), alopecia (57.1%). In our study it was to found that women with dermatological manifestations like acne and androgenic alopecia with regular menstruation. In our study it was found that these women with have high prevalence of PCOS.


Subject(s)
Acne Vulgaris , Polycystic Ovary Syndrome , Young Adult , Adolescent , Humans , Female , Adult , Middle Aged , Polycystic Ovary Syndrome/complications , Polycystic Ovary Syndrome/diagnostic imaging , Polycystic Ovary Syndrome/epidemiology , Hirsutism/epidemiology , Alopecia/diagnostic imaging , Alopecia/epidemiology , Acne Vulgaris/diagnostic imaging , Acne Vulgaris/epidemiology , Acne Vulgaris/pathology
3.
Med J Malaysia ; 78(7): 870-875, 2023 Dec.
Article in English | MEDLINE | ID: mdl-38159920

ABSTRACT

INTRODUCTION: The aim of this study was to analyse the clinical characteristics of patients with rheumatoid arthritis receiving biologics therapy and investigate the association between types of biologics and tuberculosis (TB) infections in 13 tertiary hospitals in Malaysia. MATERIALS AND METHODS: This was a retrospective study that included all RA patients receiving biologics therapy in 13 tertiary hospitals in Malaysia from January 2008 to December 2018. RESULTS: We had 735 RA patients who received biologics therapy. Twenty-one of the 735 patients were diagnosed with TB infection after treatment with biologics. The calculated prevalence of TB infection in RA patients treated with biologics was 2.9% (29 per 1000 patients). Four groups of biologics were used in our patient cohort: monoclonal TNF inhibitors, etanercept, tocilizumab, and rituximab, with monoclonal TNF inhibitors being the most commonly used biologic. The median duration of biologics therapy before the diagnosis of TB was 8 months. 75% of patients had at least one co-morbidity and all patients had at least one ongoing cDMARD therapy at the time of TB diagnosis. More than half of the patients were on steroid therapy with an average prednisolone dose of 5 mg daily. CONCLUSION: Although the study population and data were limited, this study illustrates the spectrum of TB infections in RA patients receiving biologics and potential risk factors associated with biologics therapy in Malaysia.


Subject(s)
Arthritis, Rheumatoid , Biological Products , Tuberculosis , Humans , Arthritis, Rheumatoid/drug therapy , Biological Products/adverse effects , Malaysia/epidemiology , Retrospective Studies , Tuberculosis/epidemiology , Tumor Necrosis Factor Inhibitors/adverse effects
4.
Mol Reprod Dev ; 89(1): 23-38, 2022 01.
Article in English | MEDLINE | ID: mdl-34911155

ABSTRACT

Ovulatory follicle development and associated oocyte maturation involve complex coordinated molecular and cellular mechanisms not yet fully understood. This study addresses the relationships among follicle diameter, follicle wall blood flow, follicular-fluid factors, and gene expression for follicle growth, steroidogenesis, angiogenesis, and apoptosis in granulosa/cumulus cells and oocytes during different stages from the beginning of largest/ovulatory follicle to impending ovulation in mares. The most remarkable findings were (i) a positive association between follicle development, follicle blood flow, intrafollicular follicle-stimulating hormone (FSH), luteinizing hormone (LH), estradiol, progesterone, and messenger RNA (mRNA) expression for FSHR and LHCGR in granulosa cells of the largest/ovulatory follicle; (ii) a plateau or decrease in follicle diameter and blood flow and granulosa cell mRNA for FSHR, LHCGR, IGF1R, VEGFR2, CYP19A1, and CASP3 at the preovulatory stage; (iii) higher StAR and BCL2 and lower CASP3 mRNA in granulosa cells at the time of impending ovulation; (iv) greater IGF1R mRNA for granulosa cells at the predeviation stage; and (v) lower FSHR, LHCGR, IGF1R, and VEGFR2 mRNA in cumulus cells and greater LHCGR and IGF1R mRNA in oocytes at the ovulatory stage. This study is a critical advance in the understanding of molecular mechanisms of follicle development and oocyte maturation and is expected to be vital for future studies targeting potential markers.


Subject(s)
Follicle Stimulating Hormone , Granulosa Cells , Animals , Estradiol/metabolism , Female , Follicle Stimulating Hormone/metabolism , Gene Expression , Granulosa Cells/metabolism , Hemodynamics , Horses , Ovarian Follicle/metabolism
5.
Proc Natl Acad Sci U S A ; 116(39): 19593-19599, 2019 09 24.
Article in English | MEDLINE | ID: mdl-31501324

ABSTRACT

DNA repair is critical for genome stability and is maintained through conserved pathways. Traditional genome-wide mammalian screens are both expensive and laborious. However, computational approaches circumvent these limitations and are a powerful tool to identify new DNA repair factors. By analyzing the evolutionary relationships between genes in the major DNA repair pathways, we uncovered functional relationships between individual genes and identified partners. Here we ranked 17,487 mammalian genes for coevolution with 6 distinct DNA repair pathways. Direct comparison to genetic screens for homologous recombination or Fanconi anemia factors indicates that our evolution-based screen is comparable, if not superior, to traditional screening approaches. Demonstrating the utility of our strategy, we identify a role for the DNA damage-induced apoptosis suppressor (DDIAS) gene in double-strand break repair based on its coevolution with homologous recombination. DDIAS knockdown results in DNA double-strand breaks, indicated by ATM kinase activation and 53BP1 foci induction. Additionally, DDIAS-depleted cells are deficient for homologous recombination. Our results reveal that evolutionary analysis is a powerful tool to uncover novel factors and functional relationships in DNA repair.


Subject(s)
DNA Repair/genetics , Genome-Wide Association Study/methods , Animals , Apoptosis Regulatory Proteins/genetics , Apoptosis Regulatory Proteins/metabolism , Cell Cycle Proteins/genetics , Cell Cycle Proteins/metabolism , DNA Breaks, Double-Stranded , Evolution, Molecular , Genomic Instability/genetics , Homologous Recombination/genetics , Humans , Rad51 Recombinase/genetics , Rad51 Recombinase/metabolism
6.
Molecules ; 27(5)2022 Mar 07.
Article in English | MEDLINE | ID: mdl-35268826

ABSTRACT

Oral diseases pose a major threat to public health across the globe. Diseases such as dental caries, periodontitis, gingivitis, halitosis, and oral cancer affect people of all age groups. Moreover, unhealthy diet practices and the presence of comorbidities aggravate the problem even further. Traditional practices such as the use of miswak for oral hygiene and cloves for toothache have been used for a long time. The present review exhaustively explains the potential of natural products obtained from different sources for the prevention and treatment of dental diseases. Additionally, natural medicine has shown activity in preventing bacterial biofilm resistance and can be one of the major forerunners in the treatment of oral infections. However, in spite of the enormous potential, it is a less explored area due to many setbacks, such as unfavorable physicochemical and pharmacokinetic properties. Nanotechnology has led to many advances in the dental industry, with various applications ranging from maintenance to restoration. However, can nanotechnology help in enhancing the safety and efficacy of natural products? The present review discusses these issues in detail.


Subject(s)
Oral Health
7.
Molecules ; 27(5)2022 Feb 23.
Article in English | MEDLINE | ID: mdl-35268608

ABSTRACT

Hepatitis E virus (HEV) is an understudied pathogen that causes infection through fecal contaminated drinking water and is prominently found in South Asian countries. The virus affects ~20 million people annually, leading to ~60,000 infections per year. The positive-stranded RNA genome of the HEV genotype 1 has four conserved open reading frames (ORFs), of which ORF1 encodes a polyprotein of 180 kDa in size, which is processed into four non-structural enzymes: methyltransferase (MTase), papain-like cysteine protease, RNA-dependent RNA polymerase, and RNA helicase. MTase is known to methylate guanosine triphosphate at the 5'-end of viral RNA, thereby preventing its degradation by host nucleases. In the present study, we cloned, expressed, and purified MTase spanning 33-353 amino acids of HEV genotype 1. The activity of the purified enzyme and the conformational changes were established through biochemical and biophysical studies. The binding affinity of MTase with magnesium ions (Mg2+) was studied by isothermal calorimetry (ITC), microscale thermophoresis (MST), far-UV CD analysis and, fluorescence quenching. In summary, a short stretch of nucleotides has been cloned, coding for the HEV MTase of 37 kDa, which binds Mg2+ and modulate its activity. The chelation of magnesium reversed the changes, confirming its role in enzyme activity.


Subject(s)
Hepatitis E virus
8.
Mol Carcinog ; 60(11): 769-783, 2021 11.
Article in English | MEDLINE | ID: mdl-34437731

ABSTRACT

Although CAMKK2 is overexpressed in several cancers, its role and relevant downstream signaling pathways in gastric cancer (GC) are poorly understood. Treatment of AGS GC cells with a CAMKK2 inhibitor, STO-609, resulted in decreased cell proliferation, cell migration, invasion, colony-forming ability, and G1/S-phase arrest. Quantitative phosphoproteomics in AGS cells with the CAMKK2 inhibitor led to the identification of 9603 unique phosphosites mapping to 3120 proteins. We observed decreased phosphorylation of 1101 phosphopeptides (1.5-fold) corresponding to 752 proteins upon CAMKK2 inhibition. Bioinformatics analysis of hypo-phosphorylated proteins revealed enrichment of MAPK1/MAPK3 signaling. Kinase enrichment analysis of hypo-phosphorylated proteins using the X2K Web tool identified ERK1, cyclin-dependant kinase 1 (CDK1), and CDK2 as downstream substrates of CAMKK2. Moreover, inhibition of CAMKK2 and MEK1 resulted in decreased phosphorylation of ERK1, CDK1, MCM2, and MCM3. Immunofluorescence results were in concordance with our mass spectroscopy data and Western blot analysis results. Taken together, our data reveal the essential role of CAMKK2 in the pathobiology of GC through the activation of the MEK/ERK1 signaling cascade.


Subject(s)
Benzimidazoles/pharmacology , Calcium-Calmodulin-Dependent Protein Kinase Kinase/metabolism , Naphthalimides/pharmacology , Proteomics/methods , Stomach Neoplasms/metabolism , CDC2 Protein Kinase/metabolism , Calcium-Calmodulin-Dependent Protein Kinase Kinase/antagonists & inhibitors , Cell Line, Tumor , Cell Movement/drug effects , Cell Proliferation/drug effects , Chromatography, Liquid , Cyclin-Dependent Kinase 2/metabolism , G1 Phase Cell Cycle Checkpoints/drug effects , Gene Expression Regulation, Neoplastic/drug effects , Humans , MAP Kinase Signaling System/drug effects , Phosphorylation/drug effects , Stomach Neoplasms/drug therapy , Stomach Neoplasms/genetics , Tandem Mass Spectrometry
9.
Soft Matter ; 17(8): 2034-2041, 2021 Mar 04.
Article in English | MEDLINE | ID: mdl-33443510

ABSTRACT

Droplets are spherical due to the principle of interfacial energy minimization. Here, we show that nonequilibrium droplet shapes can be stabilized via the interfacial self-assembly and crosslinking of nanoparticles. This principle allows for the stability of practically infinitely long liquid tubules and monodisperse cylindrical droplets. Droplets of oil-in-water are elongated via gravitational or hydrodynamic forces at a reduced interfacial tension. Silica nanoparticles self-assemble and cross-link on the interface triggered by the synergistic surface modification with hexyltrimethylammonium- and trivalent lanthanum-cations. The droplet length dependence is described by a scaling relationship and the rate of nanoparticle deposition on the droplets is estimated. Our approach potentially enables the 3D-printing of Newtonian Fluids, broadening the array of material options for additive manufacturing techniques.

10.
Med J Malaysia ; 76(4): 488-492, 2021 07.
Article in English | MEDLINE | ID: mdl-34305109

ABSTRACT

INTRODUCTION: The purpose of this study was to analyse the clinical characteristics of patients with idiopathic inflammatory myopathy (IIM) in Hospital Sultanah Nurzahirah (HSNZ), Terengganu, Malaysia. It also aimed to describe the disease manifestations in association with malignancy and other CTD. METHODS: This was a retrospective descriptive study involving all IIM patients who were managed by the Rheumatology Unit HSNZ from January 2010 to December 2019. RESULTS: In this review we described 15 cases wherein malignancy was detected in 4 patients after the diagnosis of IIM was made and 4 patients with overlap syndrome. One third of patients with malignancy and overlap syndrome had poor treatment response and succumbed to complications of the disease. Almost all of patients received corticosteroid as the first line therapy and nearly two thirds of them responded well to either corticosteroid alone or with combination therapy. CONCLUSION: Although this study did not represent the whole population in Malaysia, it does provide a better understanding of the disease manifestation, treatment and disease complications in our cohort of patients.


Subject(s)
Myositis , Adrenal Cortex Hormones , Cohort Studies , Humans , Malaysia/epidemiology , Myositis/diagnosis , Myositis/drug therapy , Myositis/epidemiology , Retrospective Studies
11.
Indian J Clin Biochem ; 36(3): 278-287, 2021 Jul.
Article in English | MEDLINE | ID: mdl-34220002

ABSTRACT

Human polycystic ovary syndrome (PCOS)-a cluster of diseases displays various symptoms associated with endocrine and gynecological disorders in childbearing women. Oral contraceptive pills (OCP) being a drug of choice minimizes symptoms and complications associated with the disorder. But, the controversial data available in literature regarding use of OCPs compels us to setup a study design regarding effect of OCP treatment in PCOS subjects and the possible outcomes specifically regarding coagulation pathways. Two PCOS study groups have been selected according to Rotterdam Criteria: one with OCP treatment (n = 50) and other without any drug treatment i.e., drug naive (n = 50). Anthropometry, Biochemistry, Hormones, Insulin and various clotting factors like Factor XI, Factor V, tPA, TAT-III and D-dimer were analyzed in both groups. The results showed worsening of IR, Metabolic parameters and coagulopathy in OCP group comparative to drug naive group indicating adverse effects of the OCP treatment which puts these women at risk for number of future clinical implications especially Cardiovascular and metabolic complications.

12.
Catheter Cardiovasc Interv ; 95(6): 1076-1084, 2020 05 01.
Article in English | MEDLINE | ID: mdl-31489742

ABSTRACT

OBJECTIVES: To evaluate the long-term safety and efficacy of the novel combined sirolimus-eluting endothelial progenitor cell capture Combo stent (OrbusNeich, Fort Lauderdale, FL) at 5 years in the REMEDEE (Randomized study to Evaluate the safety and effectiveness of an abluMinal sirolimus coated bio-Engineered stEnt) trial. BACKGROUND: Drug-eluting stents have limited restenosis and reintervention but are complicated by late and very late thrombosis and accelerated neoatherosclerosis. Alternative or adjunctive technologies are needed to address these limitations. METHODS: A total of 183 patients with de novo lesions in native coronary arteries were randomized 2:1 to Combo (n = 124) or Taxus Liberté (n = 59). Primary endpoint was 9 month angiographic in-stent late lumen loss and the secondary endpoint was the occurrence of major adverse events (MACE) through 5-year follow-up. RESULTS: Compared with Taxus, after 5 years the Combo stent was associated with similar rates of MACE (18.3% vs. 16.9%, p = .89), cardiac death (0.8% vs. 5.1%, p = .07), myocardial infarction (4.1% vs. 3.4%, p = .81), target lesion (9.4% vs. 10.2%, p = .78), and target vessel revascularization (14.4% vs. 11.9%, p = .73). No cases of definite stent thrombosis were reported in the Combo group. The follow-up rate at 5 years was 97.7%. CONCLUSION: At 5-year follow-up, the Combo stent remained clinically safe and effective with an overall low rate of MACE comparable to Taxus.


Subject(s)
Cardiovascular Agents/administration & dosage , Coronary Artery Disease/therapy , Drug-Eluting Stents , Endothelial Progenitor Cells/pathology , Percutaneous Coronary Intervention/instrumentation , Sirolimus/administration & dosage , Aged , Cardiovascular Agents/adverse effects , Coronary Artery Disease/diagnostic imaging , Coronary Artery Disease/mortality , Coronary Artery Disease/pathology , Coronary Restenosis/etiology , Coronary Thrombosis/etiology , Female , Humans , Male , Middle Aged , Percutaneous Coronary Intervention/adverse effects , Percutaneous Coronary Intervention/mortality , Prospective Studies , Risk Factors , Sirolimus/adverse effects , Time Factors , Treatment Outcome
13.
J Appl Toxicol ; 40(10): 1410-1420, 2020 10.
Article in English | MEDLINE | ID: mdl-32346888

ABSTRACT

Globally, more than a billion people smoke tobacco making it one of the biggest public health problems and a leading risk factor for global deaths. Nicotine, the main alkaloid in tobacco, has been shown to be associated with fertility problems in men and women. The adverse effects of tobacco/nicotine on reproduction have been attributed to deleterious effects on gametes, steroidogenic imbalance, and competitive inhibition of steroid receptors. The present study reports the sex-steroid receptor disrupting potential of nicotine and its major metabolite cotinine against the estrogen receptor-α (ERα), ERß, androgen receptor (AR), and progesterone receptor (PR). Both ligands bound in the ligand-binding pockets of ERα, ERß, AR and PR and formed important hydrophobic interactions with different amino-acid residues of receptors. Most of the residues of ERα, ERß, AR and PR interacting with nicotine and cotinine were common with those of native/bound ligands of the receptors. Interacting amino acids most important for binding of nicotine and cotinine with each receptor were identified by loss in accessible surface area. Amino acids Leucine-346, Leucine-384 and Phenylalanine-404 for ERα; Methionine-336, Phenylalanine-356 and Leucine-298 for ERß; and Leucine-704 and Leucine-718, respectively for AR and PR, were the most important residues for binding with nicotine and cotinine. Among the four receptors, based on the number of interactions, nicotine and cotinine had greater potential to interfere in the signaling of ERß. In conclusion, the results suggested that nicotine and cotinine bind and interact with sex-steroid nuclear receptors and have potential to interfere in the steroid hormone signaling resulting in reproductive dysfunction.


Subject(s)
Binding Sites/drug effects , Cotinine/toxicity , Molecular Structure , Nicotine/toxicity , Receptors, Estrogen/drug effects , Receptors, Progesterone/drug effects , Receptors, Progesterone/metabolism , Adult , Female , Humans , Male , Middle Aged , Receptors, Estrogen/metabolism , Nicotiana/chemistry
14.
J Appl Toxicol ; 40(6): 832-842, 2020 06.
Article in English | MEDLINE | ID: mdl-32003036

ABSTRACT

Tetrabromobisphenol A (TBBPA) is a widely used brominated flame retardant owing to its efficient fire-breaking property. However, leaching of TBBPA into the environment has been a global health concern due to the endocrine-disrupting activity (EDA) associated with TBBPA exposure. Limited studies are available on the hazardous effects of TBBPA on reproductive function. The aim of the present study was the structural characterization of potential EDA of TBBPA in reproductive hormone signaling and transport including steroid nuclear receptors, such as estrogen receptor alpha (ERα), estrogen receptor beta (ERß), androgen receptor (AR), progesterone receptor (PR), and the steroid transport protein, sex hormone-binding globulin (SHBG). The structural binding characterization of TBBPA with the sex steroid nuclear receptors and transport protein was performed by induced-fit docking using the Schrödinger 2017 suite. The results revealed that the TBBPA binding pattern and molecular interactions with the indicated receptors and transport protein displayed overall similarity with their respective native ligands. The estimated binding energy value of TBBPA for ERα was similar to the native ligand, estradiol, indicating tight binding and greater potential for TBBPA to disrupt ERα signaling. For ERß, AR, PR and SHBG, the estimated binding energy values were also close to their respective native ligands, indicating potential for interference in native hormone signaling and transport. In conclusion, TBBPA exposure in humans may potentially cause disruption of sex steroid signaling and transport, and thus lead to reproductive dysfunction.


Subject(s)
Endocrine Disruptors/chemistry , Endocrine Disruptors/metabolism , Flame Retardants/metabolism , Gonadal Steroid Hormones/metabolism , Molecular Docking Simulation , Polybrominated Biphenyls/metabolism , Receptors, Steroid/metabolism , Sex Hormone-Binding Globulin/metabolism , Databases, Protein , Endocrine Disruptors/toxicity , Estrogen Receptor alpha/metabolism , Estrogen Receptor beta/metabolism , Flame Retardants/toxicity , Humans , Ligands , Polybrominated Biphenyls/chemistry , Polybrominated Biphenyls/toxicity , Protein Binding , Protein Conformation , Receptors, Androgen/metabolism , Receptors, Progesterone/metabolism , Sex Hormone-Binding Globulin/chemistry , Structure-Activity Relationship
15.
Phytother Res ; 34(4): 825-835, 2020 Apr.
Article in English | MEDLINE | ID: mdl-31769107

ABSTRACT

Acute pancreatitis (AP) is a disorder of the pancreas marked by profound inflammation and oxidative stress. Phytoconstituents presents an important toolbox of preventive strategies to combat inflammatory disorders. To this end, we selected the active constituent of Crocus sativus, crocin for evaluation against cerulein-induced AP, owing to its promising antiinflammatory activity in acute as well as chronic inflammatory conditions. The animals were randomly divided into five groups comprising of normal control, cerulein control, crocin low dose (30 mg/kg), crocin high dose (100 mg/kg), and crocin control (100 mg/kg). Various biochemical parameters and the levels of inflammatory cytokines and p65-NFκB were measured. The mechanism was investigated by histology and immunohistochemistry. We found that crocin significantly reduced the pancreatic edema, amylase, and lipase levels. It abrogated the oxidative stress incurred by cerulein challenge. We found that crocin modulated the pancreatic inflammatory cytokine levels. Crocin perturbed the nuclear translocation of p65-NFκB. Crocin reverted the pancreatic histology associated with AP. Furthermore, it upregulated the expression of Nrf-2 and downregulated the expression of IL-6, TNF-α, nitrotyrosine, and NFκB. Cumulatively, these results indicate that crocin has promising potential to prevent cerulein induced AP and regular intake of saffron can prove beneficial for the pancreatic health.


Subject(s)
Anti-Inflammatory Agents/pharmacology , Carotenoids/pharmacology , Ceruletide/toxicity , Oxidative Stress/drug effects , Pancreatitis/chemically induced , Pancreatitis/prevention & control , Acute Disease , Animals , Anti-Inflammatory Agents/isolation & purification , Carotenoids/isolation & purification , Crocus/chemistry , Cytoprotection/drug effects , Male , Mice , Pancreas/drug effects , Pancreas/pathology , Pancreatitis/metabolism , Pancreatitis/pathology , Phytotherapy
16.
Toxicol Ind Health ; 36(5): 322-335, 2020 May.
Article in English | MEDLINE | ID: mdl-32496146

ABSTRACT

Many bisphenol A (BPA) analogs have been commercially used recently, such as 2,2-bis(4-hydroxyphenyl)butane (BPB), 4,4'-ethylidenebisphenol, 4,4'-methylenediphenol (BPF), 4,4'-(1,4-phenylenediisopropylidene)bisphenol (BPP), 4,4'-dihydroxydiphenyl sulfone (BPS), 4,4'-cyclohexylidenebisphenol (BPZ), 4,4'-(hexafluoroisopropylidene)diphenol (BPAF), 4,4'-(1-phenylethylidene)bisphenol (BPAP), and 2,2-bis(4-hydroxy-3,5-dimethylphenyl)propane (TMBPA), to circumvent adverse effects of BPA. However, their increasing use is also contaminating the environment, which is a potential cause of concern for human health. Thyroid hormone transport and signaling are potential targets for endocrine-disrupting activity of BPA analogs. Thyroxine-binding globulin (TBG) is the major carrier protein for thyroxine (T4) and triiodothyronine (T3) in blood. Thyroid hormones exert their action through thyroid hormone receptors (TRα and TRß). This report presents the thyroid-disrupting potential of indicated nine BPA analogs from structure-based studies with TBG and TRα. Each BPA analog formed important polar and hydrophobic interactions with a number of residues of TBG and TRα. Majority of TBG residues (77-100%) and TRα residues (70-91%) interacting with BPA analogs were common with those of native ligands T4 and T3, respectively. Majority of BPA analogs interacted with TBG forming a salt bridge interaction at Lys-270. The hydrogen-bonding interaction of T3 with TRα at His-381 was also shared by majority of analogs. The binding energy for BPP, BPB, BPZ, BPAP, and TMBPA with both proteins was closer to binding energy of respective native ligands. The similarity in structural binding characteristics suggested potential disrupting activity of thyroid hormone signaling and transport.


Subject(s)
Benzhydryl Compounds/adverse effects , Endocrine Disruptors/adverse effects , Environmental Exposure/adverse effects , Phenols/adverse effects , Receptors, Thyroid Hormone/metabolism , Thyroxine-Binding Globulin/metabolism , Humans , Molecular Docking Simulation
17.
Molecules ; 25(21)2020 Nov 03.
Article in English | MEDLINE | ID: mdl-33152997

ABSTRACT

Deep eutectic solvents (DESs) are green solvents developed as an alternative to conventional organic solvents and ionic liquids to extract nitrogen compounds from fuel oil. DESs based on p-toluenesulfonic acid (PTSA) are a new solvent class still under investigation for extraction/separation. This study investigated a new DES formed from a combination of tetrabutylphosphonium bromide (TBPBr) and PTSA at a 1:1 molar ratio. Two sets of ternary liquid-liquid equilibrium experiments were performed with different feed concentrations of nitrogen compounds ranging up to 20 mol% in gasoline and diesel model fuel oils. More than 99% of quinoline was extracted from heptane and pentadecane using the DES, leaving the minutest amount of the contaminant. Selectivity was up to 11,000 for the heptane system and up to 24,000 for the pentadecane system at room temperature. The raffinate phase's proton nuclear magnetic resonance (1H-NMR) spectroscopy and GC analysis identified a significantly small amount of quinoline. The selectivity toward quinoline was significantly high at low solute concentrations. The root-mean-square deviation between experimental data and the non-random two-liquid (NRTL) model was 1.12% and 0.31% with heptane and pentadecane, respectively. The results showed that the TBPBr/PTSADES is considerably efficient in eliminating nitrogen compounds from fuel oil.


Subject(s)
Benzenesulfonates/chemistry , Gasoline , Models, Chemical , Ionic Liquids/chemistry , Solvents/chemistry
18.
Pharm Dev Technol ; 25(9): 1031-1042, 2020 Nov.
Article in English | MEDLINE | ID: mdl-32538215

ABSTRACT

The aim of this study was to formulate and evaluate SR matrix pellets containing losartan potassium (LP) solid dispersion using extrusion-spheronization technique to minimize the fluctuation of its plasma concentration. LP solid dispersions were prepared by using different hydrophobic polymers at different weight ratios (0.5, 1, 2, and 5%). LP-Eudragit RS solid dispersion at 1:5 ratio resulted in slower drug release (only 20% of LP was released in about 8 h). Different concentrations of hydrophilic polymer, PEG 6000, were mixed with Avicel® PH 101 to prepare the LP SR matrix pellets containing solid dispersion using 32 full factorial design to evaluate the effects of formulation parameters on the pellets attributes. The magnitude of torque for the pellet wet masses and binder ratio were decreased significantly with increasing PEG 6000 concentration. LP sustained release pellet formula composed of 9.24% PEG 6000 and 8 × 10-9% PVP K30 solution was chosen as optimized formula. Pharmacokinetic studies revealed that calculated t max was 9.72 ± 2.22 h from the optimized sustained release pellets compared to 2.11 ± 0.49 h in case of Cozaar® immediate release tablet, indicating a slower release of the LP from pellets.


Subject(s)
Delayed-Action Preparations/chemistry , Drug Implants/chemistry , Losartan/chemistry , Acrylic Resins/chemistry , Animals , Cellulose/chemistry , Chemistry, Pharmaceutical/methods , Delayed-Action Preparations/pharmacokinetics , Drug Implants/pharmacokinetics , Hydrophobic and Hydrophilic Interactions , Losartan/pharmacokinetics , Male , Molecular Weight , Polyethylene Glycols/chemistry , Polymers/chemistry , Rabbits , Solubility/drug effects , Tablets/chemistry , Tablets/pharmacokinetics
19.
Angew Chem Int Ed Engl ; 59(35): 14802-14808, 2020 Aug 24.
Article in English | MEDLINE | ID: mdl-32449822

ABSTRACT

The major challenge in solar water splitting to H2 and O2 is in making a stable and affordable system for large-scale applications. We have designed, fabricated, and tested a photoelectrochemical reactor characterized as follows: 1) it comprises an integrated device to reduce the balance of the system cost, 2) it utilizes concentrated sunlight to reduce the photoabsorber cost, and 3) it employs and alkaline electrolyte to reduce catalyst cost and eliminate external thermal management needs. The system consists of an III-V-based photovoltaic cell integrated with Ni foil as an O2 evolution catalyst that also protects the cell from corrosion. At low light concentration, without the use of optical lenses, the solar-to-hydrogen (STH) efficiency was 18.3 %, while at high light concentration (up to 207 suns) with the use of optical lenses, the STH efficiency was 13 %. Catalytic tests conducted for over 100 hours at 100-200 suns showed no sign of degradation nor deviation from product stoichiometry (H2 /O2 =2). Further tests projected a system stability of years.

20.
Andrologia ; 51(6): e13272, 2019 Jul.
Article in English | MEDLINE | ID: mdl-30907014

ABSTRACT

In recent years, genetic studies have yielded great progress in elucidating causes of male infertility. This investigation aims to identify frequent genetic abnormalities, that is, sex chromosome aneuploidies and Y-chromosome microdeletions among infertile men in Western Saudi Arabia. From a population of infertile patients, 88 male patients with either azoospermia or severe oligozoospermia (sperm concentration <5 million/ml) were selected. In addition to a thorough clinical workup, karyotypes and Y-chromosomal microdeletions were investigated. Among those 88 infertile patients, we detected six patients with Klinefelter syndrome, two with 47 XYY syndrome and two with Y-chromosome microdeletions AZFb,c. While the prevalence of sex chromosome aneuploidies was in the range of globally investigated populations, the microdeletions appeared to be less frequent in Western Saudi Arabia compared to other regions of the world. All genetically abnormal cases showed sperm concentration <1 million/ml, and hence, this appears to be the threshold for warranting genetic investigations in Western Saudi Arabia. Since Klinefelter and 47 XYY syndromes were only discovered late in life, upon an infertility investigation, sex chromosome aneuploidies due to their many-fold comorbidities require earlier medical attention. A neonatal screening programme is suggested for detection of these aneuploidies in Saudi Arabia for the general health benefit of these patients.


Subject(s)
Aneuploidy , Infertility, Male/epidemiology , Klinefelter Syndrome/epidemiology , Sex Chromosome Disorders of Sex Development/epidemiology , Adult , Chromosome Deletion , Chromosomes, Human, Y/genetics , Genetic Testing/methods , Health Services Needs and Demand , Humans , Incidence , Infertility, Male/diagnosis , Infertility, Male/genetics , Karyotyping , Klinefelter Syndrome/diagnosis , Klinefelter Syndrome/genetics , Male , Mass Screening/methods , Mass Screening/organization & administration , Middle Aged , Prospective Studies , Saudi Arabia/epidemiology , Sex Chromosome Aberrations , Sex Chromosome Disorders of Sex Development/diagnosis , Sex Chromosome Disorders of Sex Development/genetics , Sperm Count
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