Publications by authors named "Khalid Hussain"

320 Publications

In vitro antioxidant potential and antiproliferative activity of Aesculus indica seed extract against hepatocellular carcinoma cell line.

Pak J Pharm Sci 2021 Jan;34(1(Supplementary)):301-306

School of Biological Sciences, University of the Punjab, Quaid-e-Azam Campus, Lahore, Pakistan.

Therapeutic secondary metabolites have gained immense attention in recent years due to their effective medicinal properties. Aesculus indica is a medicinally important plant being traditionally used for various ailments. The present study aimed to determine the antioxidant and antiproliferative activities of seeds of A. indica. The crude methanolic seed extract was prepared and subjected to sequential fractionation in increasing polarity. The extract and its fractions were investigated for antioxidant activities using various in vitro assays. Further, the extract along with its potential antioxidant fractions were analyzed for their cytotoxic activity against HepG2, human hepatocyte carcinoma cells through bioassays. The results showed highly significant antioxidant potential of methanolic extract of A. indica seeds and two of its fractions prepared with chloroform and ethyl acetate. The studies on hepatocyte carcinoma cells further revealed that the extract and two of its potential antioxidant fractions significantly induced cytotoxicity and inhibited migration, proliferation, clonogenicity and 3D growth of HepG2 cells. It is therefore, concluded that A. indica possess significant antioxidant and cytotoxic potential against HepG2 cells and with further research can be proposed for therapeutic interventions.
View Article and Find Full Text PDF

Download full-text PDF

Source
January 2021

Ga-NODAGA-exendin-4 PET improves the detection of focal congenital hyperinsulinism.

J Nucl Med 2021 Jul 2. Epub 2021 Jul 2.

Radboud University Medical Center, Netherlands.

Surgery with curative intent can be offered to Congenital Hyperinsulinism (CHI) patients, provided that the lesion is focal. Radiolabeled Exendin-4 specifically binds the glucagon-like peptide 1 receptor (GLP-1R) on pancreatic beta cells. In this study we compared the performance of [F]F-DOPA positron emission tomography/computed tomography (DOPA PET) and PET/CT with the new tracer [Ga]Ga-NODAGA-exendin-4 (Exendin PET) in the preoperative detection of focal CHI. Nineteen CHI patients underwent both DOPA PET and Exendin PET prior to surgery. The images were evaluated in three settings a) standard clinical reading b) blinded expert reading and c) joined reading. Target (lesion) / non target (normal pancreas) ratio were determined using maximum standard uptake value (SUV). Image quality was rated by pediatric surgeons in a questionnaire. Fourteen/nineteen patients having focal lesions underwent surgery. Based on clinical readings, the sensitivity of Exendin PET (100% (CI 77-100%)) was higher than that of DOPA PET (71% (CI 42-92%)). Interobserver agreement between readings was higher for Exendin than for DOPA PET (Fleiss' kappa 0.91 vs. 0.56). Exendin PET provided significantly ( = 0.021) higher target / non target ratios (2.02 ± 0.65 ) than DOPA PET (1.40 ± 0.40). On a five point scale, Pediatric surgeons rated Exendin PET superior to DOPA PET. Exendin PET has higher clinical sensitivity and better interobserver correlation for the detection of focal CHI than DOPA PET. Better contrast and image quality makes Exendin PET superior to DOPA PET in surgeons' intra-operative quest for lesion localization.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2967/jnumed.121.262327DOI Listing
July 2021

An induced pluripotent stem cell line derived from a patient with neonatal diabetes and Fanconi-Bickel syndrome caused by a homozygous mutation in the SLC2A2 gene.

Stem Cell Res 2021 07 21;54:102433. Epub 2021 Jun 21.

Diabetes Research Center (DRC), Qatar Biomedical Research Institute (QBRI), Hamad Bin Khalifa University (HBKU), Qatar Foundation (QF), PO Box 34110, Doha, Qatar; College of Health and Life Sciences, Hamad Bin Khalifa University (HBKU), Qatar Foundation, Education City, Doha, Qatar. Electronic address:

Recessive mutations in the glucose transporter gene SLC2A2 (GLUT2) lead to permanent neonatal diabetes (PNDM) and Fanconi Bickel Syndrome (FBS). Here, we generated an induced pluripotent stem cell (iPSC) line, QBRIi012-A, from a 24-month-old boy with FBS and PNDM due to homozygous nonsense mutation in the SLC2A2 gene (c.901C > T). The QBRIi012-A was fully characterized using different approaches. The cell line showed normal karyotype and was able to differentiate into the three germ layers in vitro. This iPSC line provides a novel human cell model to understand the pathophysiology of FBS and diabetes associated with SLC2A2 defects.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.scr.2021.102433DOI Listing
July 2021

GHRH secretion from a pancreatic neuroendocrine tumor causing gigantism in a patient with MEN1.

Endocrinol Diabetes Metab Case Rep 2021 Jun 1;2021. Epub 2021 Jun 1.

Department of Endocrinology, Barts and the London School of Medicine and Dentistry, William Harvey Research Institute, Queen Mary University of London, London, UK.

Summary: A male patient with a germline mutation in MEN1 presented at the age of 18 with classical features of gigantism. Previously, he had undergone resection of an insulin-secreting pancreatic neuroendocrine tumour (pNET) at the age of 10 years and had subtotal parathyroidectomy due to primary hyperparathyroidism at the age of 15 years. He was found to have significantly elevated serum IGF-1, GH, GHRH and calcitonin levels. Pituitary MRI showed an overall bulky gland with a 3 mm hypoechoic area. Abdominal MRI showed a 27 mm mass in the head of the pancreas and a 6 mm lesion in the tail. Lanreotide-Autogel 120 mg/month reduced GHRH by 45% and IGF-1 by 20%. Following pancreaticoduodenectomy, four NETs were identified with positive GHRH and calcitonin staining and Ki-67 index of 2% in the largest lesion. The pancreas tail lesion was not removed. Post-operatively, GHRH and calcitonin levels were undetectable, IGF-1 levels normalised and GH suppressed normally on glucose challenge. Post-operative fasting glucose and HbA1c levels have remained normal at the last check-up. While adolescent-onset cases of GHRH-secreting pNETs have been described, to the best of our knowledge, this is the first reported case of ectopic GHRH in a paediatric setting leading to gigantism in a patient with MEN1. Our case highlights the importance of distinguishing between pituitary and ectopic causes of gigantism, especially in the setting of MEN1, where paediatric somatotroph adenomas causing gigantism are extremely rare.

Learning Points: It is important to diagnose gigantism and its underlying cause (pituitary vs ectopic) early in order to prevent further growth and avoid unnecessary pituitary surgery. The most common primary tumour sites in ectopic acromegaly include the lung (53%) and the pancreas (34%) (1): 76% of patients with a pNET secreting GHRH showed a MEN1 mutation (1). Plasma GHRH testing is readily available in international laboratories and can be a useful diagnostic tool in distinguishing between pituitary acromegaly mediated by GH and ectopic acromegaly mediated by GHRH. Positive GHRH immunostaining in the NET tissue confirms the diagnosis. Distinguishing between pituitary (somatotroph) hyperplasia secondary to ectopic GHRH and pituitary adenoma is difficult and requires specialist neuroradiology input and consideration, especially in the MEN1 setting. It is important to note that the vast majority of GHRH-secreting tumours (lung, pancreas, phaeochromocytoma) are expected to be visible on cross-sectional imaging (median diameter 55 mm) (1). Therefore, we suggest that a chest X-ray and an abdominal ultrasound checking the adrenal glands and the pancreas should be included in the routine work-up of newly diagnosed acromegaly patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1530/EDM-20-0208DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8240703PMC
June 2021

Epidemiology, genetic landscape and classification of childhood diabetes mellitus in the State of Qatar.

J Diabetes Investig 2021 Jun 8. Epub 2021 Jun 8.

Division of Endocrinology, Department of Pediatrics, Sidra Medicine, Doha, Qatar.

Aims/introduction: To study the epidemiology, genetic landscape and causes of childhood diabetes mellitus in the State of Qatar.

Materials And Methods: All patients (aged 0-18 years) with diabetes mellitus underwent biochemical, immunological and genetic testing. American Diabetes Association guidelines were used to classify types of diabetes mellitus. The incidence and prevalence of all the different types of diabetes mellitus were calculated.

Results: Total number of children with diabetes mellitus was 1,325 (type 1 n = 1,096, ≥1 antibody; type 2 n = 104, type 1B n = 53; maturity onset diabetes of the young n = 20; monogenic autoimmune n = 4; neonatal diabetes mellitus n = 10;, syndromic diabetes mellitus n = 23; and double diabetes mellitus n = 15). The incidence and prevalence of type 1 diabetes were 38.05 and 249.73 per 100,000, respectively, and for type 2 were 2.51 and 23.7 per 100,000, respectively. The incidence of neonatal diabetes mellitus was 34.4 per 1,000,000 live births, and in indigenous Qataris the incidence was 43.6 per 1,000,000 live births. The prevalence of type 1 diabetes and type 2 diabetes in Qatari children was double compared with other nationalities. The prevalence of maturity onset diabetes of the young in Qatar was 4.56 per 100,000.

Conclusions: This is the first prospective and comprehensive study to document the epidemiology and genetic landscape of childhood diabetes mellitus in this region. Qatar has the fourth highest incidence of type 1 diabetes mellitus, with the incidence and prevalence being higher in Qatari compared with non-Qatari. The prevalence of type 2 diabetes mellitus is also higher in Qatar than in Western countries. The incidence of neonatal diabetes mellitus is the second highest in the world. GCK is the most common form of maturity onset diabetes of the young, and a large number of patients have type 1B diabetes mellitus.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/jdi.13610DOI Listing
June 2021

Assessment of lower urinary tract symptoms among calcium channel blocker-users and its impact on quality of life.

J Pak Med Assoc 2021 May;71(5):1384-1387

Punjab University College of Pharmacy, University of the Punjab, Lahore, Pakistan.

Objective: To investigate the prevalence and severity of lower urinary tract symptoms among calcium channel blocker users, and the impact on patients' quality of life.

Methods: The cross-sectional study was conducted at one hospital and 2 community pharmacies in Lahore, Pakistan, from November 2017 to July 2018, and comprised patients using calcium channel blockers. Data was collected using standardised scales to assess lower urinary tract symptoms and quality of life. Data was analysed using SPSS 22.

Results: Of the 410 subjects, 315 (76.8%) were males. The overall median age was 50.84 years, IQR 19 with 126 (30.7%) aged 41-50 years. Of the total, 108 (26.3%) patients were on calcium channel blockers alone, while the rest were taking it in combination with other drugs. Prevalence of lower urinary tract symptoms was 307 (74.9%); mild 103 (25.1%), moderate 201 (49.1%) and severe 106 (25.9%). The symptoms were significantly associated with reduced quality of life (p<0.05).

Conclusion: Majority calcium channel blockers users had clinically significant lower urinary tract symptoms which significantly reduced patients' quality of life.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.47391/JPMA.1162DOI Listing
May 2021

Fixed Dose Single Tablet Formulation with Differential Release of Amlodipine Besylate and Simvastatin and Its Pharmacokinetic Profile: QbD and Risk Assessment Approach.

Drug Des Devel Ther 2021 24;15:2193-2210. Epub 2021 May 24.

Punjab University College of Pharmacy, University of the Punjab, Lahore, Pakistan.

Purpose: A differential release fixed dose matrix tablet of amlodipine besylate (AML-B) and simvastatin (SIM) was formulated to enhance patient compliance.

Material And Method: In the first phase, release controlling parameters of AML-B and SIM granules were identified and in the second phase a fixed dose AML-B and SIM tablet formulation was prepared and optimized for a differential release of the drugs using a quality by design (QbD) and risk assessment approach. A validated HPLC method was employed for simultaneous determination of AML-B and SIM for FDC formulation. A pharmacokinetics of the above drugs was studied in healthy dogs in the third phase.

Results: In QbD-based optimized formulation, Eudragit RSPO-dicalcium phosphate (DCP) blend controlled the release of AML-B over 8 h, though this diffusion-controlled release assumed first order kinetics. DCP and Eudragit RS 100 also retarded release of SIM causing SIM release over 8 h after AML-B release from the optimized FDC tablet formulation. The HPLC retention times of AML-B and SIM were 2.10 and 15.52 min, respectively. Linearity for AML-B was 5.0-50 ng/mL and 0.01-2.0 µg/mL for SIM with percent recoveries of 92.85-101.53% and 94.51-117.75% for AML-B and SIM. AUC of AML-B was increased 3 fold, while AUC of SIM was decreased 2 fold. The t values for AML-B and SIM were 12 and 6 h, respectively. AML-B was absorbed without any lag time (t) while t was 6.33 ± 0.81 h for SIM, thus met the study objective.

Conclusion: The pharmacokinetic study showed an immediate absorption of AML-B while that of SIM was withheld for 6 h, close to the desired delay time of 8 h.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2147/DDDT.S240506DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8164448PMC
May 2021

Antibiotic use among hospitalized children with lower respiratory tract infections: a multicenter, retrospective study from Punjab, Pakistan.

Expert Rev Anti Infect Ther 2021 Jul 12:1-6. Epub 2021 Jul 12.

Department of Pharmacy Administration and Clinical Pharmacy, School of Pharmacy, Xi'an Jiaotong University, Xi'an, China.

Background: Lower respiratory tract infection (LRTI) is one of the triggering factors toward death in children below the age of five years necessitating appropriate antibiotic selection. This study aimed to evaluate antibiotic use among hospitalized children (≤5 years age) with LRTIs.

Methods: A retrospective study was conducted in seven health facilities of the central region of Punjab province of Pakistan. The medical records of hospitalized children ≤5 years diagnosed with LRTI were thoroughly evaluated to get information on demographics, clinical characteristics, and details of prescribed antibiotics. The appropriateness of antibiotics was assessed according to guidelines of the British National Formulary due to a lack of indigenous standard treatment guidelines.

Results: The medical records of 5926 children were searched with the majority (70.9%) diagnosed with community-acquired pneumonia (CAP) followed by acute bronchitis (14.1%). Ceftriaxone plus ampicillin and ceftriaxone plus ampicillin plus amikacin were prescribed to 39% and 11.7% study population, respectively. One-fourth of children were prescribed the wrong dose, and more than half were encountered with the incorrect route of antibiotic administration. Alarmingly, 90.2% of antibiotic prescriptions were inappropriate in our findings.

Conclusions: Current surveillance study revealed a worrying degree of antibiotic misuse among hospitalized LRTI children aged ≤5 years.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/14787210.2021.1935235DOI Listing
July 2021

Comment on "One Year Real-World Use of the Control-IQ Advanced Hybrid Closed-Loop Technology" by Breton M and Kovatchev B.

Diabetes Technol Ther 2021 May 18. Epub 2021 May 18.

Sidra Medical and Research Center, 187187, Doha, Ad Dawhah, Qatar;

NA.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1089/dia.2021.0179DOI Listing
May 2021

Corneal confocal microscopy identifies a reduction in corneal keratocyte density and sub-basal nerves in children with type 1 diabetes mellitus.

Br J Ophthalmol 2021 Apr 30. Epub 2021 Apr 30.

Department of Medicine, Weill Cornell Medicine, Doha, Qatar

Purpose: To assess whether alterations in stromal keratocyte density are related to loss of corneal nerve fibres in children with type 1 diabetes mellitus (T1DM).

Methods: Twenty participants with T1DM and 20 age-matched healthy controls underwent corneal confocal microscopy. Corneal sub-basal nerve morphology and corneal keratocyte density (KD) were quantified.

Results: Corneal nerve fibre density (CNFD) (p<0.001), corneal nerve branch density (p<0.001), corneal nerve fibre length (CNFL) (p<0.001) and inferior whorl length (IWL) (p<0.001) were lower in children with T1DM compared with healthy controls. Anterior (p<0.03) and mid (p=0.03) stromal KDs were lower with no difference in posterior KD (PKD) in children with T1DM compared with controls. Age, duration of diabetes, height, weight and body mass index did not correlate with anterior (AKD), mid (MKD) or PKD. Inverse correlations were found between glycated haemoglobin and PKD (r=-0.539, p=0.026), bilirubin with MKD (r=-0.540, p=0.025) and PKD (r=-0.531, p=0.028) and 25-hydroxycholecalciferol with MKD (r=-0.583, p=0.018). CNFD, CNFL and IWL did not correlate with AKD, MKD or PKD.

Conclusion: This study demonstrates a reduction in corneal nerves and anterior and mid stromal KD in children with T1DM, but no correlation between corneal nerve and keratocyte cell loss.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1136/bjophthalmol-2021-319057DOI Listing
April 2021

The global research trend on cadmium in freshwater: a bibliometric review.

Environ Sci Pollut Res Int 2021 Apr 20. Epub 2021 Apr 20.

College of Food Science and Engineering, Tianjin Agricultural University, Tianjin, 300384, People's Republic of China.

Cadmium pollution turns out to be a global environmental problem. This study conducted a quantitative and qualitative bibliometric analysis based on 9188 research items from the Web of Science Core Collection published in the last 20 years (2000-2020), presenting an in-depth statistical investigation of global freshwater cadmium research progress and developing trend. Our results demonstrated that the researchers from China, the USA, and India contribute the most to this field. The primary sources of cadmium are mining, industry, wastewater, sedimentation, and agricultural activities. In developing countries, cadmium exposure occurs mainly through the air, freshwater, and food. Fish and vegetables are the main food sources of cadmium for humans because of their high accumulation capability. Source evaluation, detection, and remediation represent the main technologies used to clean up cadmium-contaminated sites. To mitigate the risk of cadmium contamination in freshwater, biomarker-based cadmium monitoring methods and integrated policies/strategies to reduce cadmium exposure merit further concern.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s11356-021-13894-7DOI Listing
April 2021

Founder mutation in the PMM2 promotor causes hyperinsulinemic hypoglycaemia/polycystic kidney disease (HIPKD).

Mol Genet Genomic Med 2021 Apr 3:e1674. Epub 2021 Apr 3.

Department Renal Medicine, University College London, London, UK.

Background: Polycystic kidney disease with hyperinsulinaemic hypoglycaemia (HIPKD) is a recently described disease caused by a single nucleotide variant, c.-167G>T, in the promoter region of PMM2 (encoding phosphomannomutase 2), either in homozygosity or compound heterozygosity with a pathogenic coding variant in trans. All patients identified so far are of European descent, suggesting a possible founder effect.

Methods: We generated high density genotyping data from 11 patients from seven unrelated families, and used this information to identify a common haplotype that included the promoter variant. We estimated the age of the promoter mutation with DMLE+ software, using demographic parameters corresponding to the European population.

Results: All patients shared a 0.312 Mb haplotype which was absent in 503 European controls available in the 1000 Genomes Project. The age of this mutation was estimated as 105-110 generations, indicating its occurrence around 600 BC, a time of intense migration, which might explain the presence of the same mutations in Europeans around the globe.

Conclusion: The shared unique haplotype among seemingly unrelated patients is consistent with a founder effect in Europeans.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/mgg3.1674DOI Listing
April 2021

The potential of microbes and sulfate in reducing arsenic phytoaccumulation by maize (Zea mays L.) plants.

Environ Geochem Health 2021 Apr 2. Epub 2021 Apr 2.

State Key Laboratory of Environmental Geochemistry, Institute of Geochemistry, Chinese Academy of Sciences, Guiyang, 550081, China.

Arsenic (As) contamination in soil-plant system is an important environmental, agricultural and health issue globally. The microbe- and sulfate-mediated As cycling in soil-plant system may depend on soil sulfate levels, and it can be used as a potential strategy to reduce plant As uptake and improve plant growth. Here, we investigated the role of soil microbes (SMs) to examine As phytoaccumulation using maize as a test plant, under varying sulfate levels (S-0, S-5, S-25 mmol kg) and As stress. The addition of sulfate and SMs promoted maize plant growth and reduced As concentration in shoots compared to sulfate-treated plants without SMs. Results revealed that the SMs-S-5 treatment proved to be the most promising in reducing As uptake by 27% and 48% in root and shoot of the maize plants, respectively. The SMs-S treatments, primarily with S-5, enhanced plant growth, shoot dry biomass, Chl a, b and total Chl (a + b) contents, and gas exchange attributes of maize plants. Similarly, the antioxidant defense in maize plants was increased significantly in SMs-S-treated plants, notably with SMs-S-5 treatment. Overall, the SMs-S-5-treated plants possessed improved plant growth, dry biomass, physiology and antioxidant defense system and decrease in plant shoot As concentration. The outcomes of this study suggest that sulfate supplementation in soil along with SMs could assist in reducing As accumulation by maize plants, thus providing a sustainable and eco-friendly bioremediation strategy in limiting As exposure.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s10653-021-00902-5DOI Listing
April 2021

Clinical and genetic characteristics of patients with congenital hyperinsulinism in 21 non-consanguineous families from Serbia.

Eur J Pediatr 2021 Mar 26. Epub 2021 Mar 26.

Department of Pediatric Endocrinology, Mother and Child Health Care Institute of Serbia "Dr Vukan Cupic", Radoja Dakica 8, Belgrade, 11070, Serbia.

Persistent hypoglycaemia in newborns and infants is most commonly caused by congenital hyperinsulinism (CHI). Most CHI studies report outcomes in children from both consanguineous and non-consanguineous families which can affect the phenotype-genotype analysis. The aim of this study was to analyze characteristics of patients with CHI in 21 non-consanguineous families from Serbia. This retrospective cohort study included a total of 21 patients with CHI treated in the Mother and Child Healthcare Institute of Serbia during the past 20 years. The prevalence of macrosomia at birth was very low in our cohort (4.8%). Median age at presentation was 6 days, with seizures as the presenting symptom in 76% of patients. Only four patients (19%) were diazoxide unresponsive, and eventually underwent pancreatectomy. Genetic testing was performed in 15 patients and genetic diagnosis was confirmed in 60%, with all patients being heterozygous for detected mutations. The ABCC8 gene mutations were detected in 55.6%, GLUD1 in three patients (33.3%) with HIHA syndrome and one patient had HNF4A gene mutation and unusual prolonged hyperglycaemia lasting 6 days after diazoxide cessation. Neurodevelopmental deficits persisted in 33% of patients.Conclusion: This is the first study regarding CHI patients in Serbia. It suggests that in countries with low consanguinity rate, majority of CHI patients are diazoxide responsive. The most common mutations were heterozygous ABCC8, followed by GLUD1 and HNF4A mutations, suggesting the potential benefit of population-tailored genetic analysis approach, targeting the mutations causing CHI via dominant inheritance model in regions with low consanguinity rates. What is Known: • Persistent hypoglycaemia during infancy and early childhood is most commonly caused by congenital hyperinsulinism (CHI). • Consanguinity is a very important factor regarding the genetics and phenotype of CHI, increasing the risk of autosomal recessive genetic disorders, including the severe, diazoxide-unresponsive forms caused by recessive inactivating mutations in ABCC8 and KCNJ11. What is New: • Results of the present study which included CHI patients from 21 non-consanguineous families suggest that in countries with low consanguinity rates, majority of CHI patients can be diazoxide responsive, with most common mutations being heterozygous ABCC8, followed by GLUD1 and HNF4A mutations. • Unusually prolonged hyperglycaemic reaction to diazoxide treatment in a patient with HNF4A mutation was also described in the present study.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00431-021-04051-wDOI Listing
March 2021

Hepatoprotective and antioxidant activity of Dicliptera bupleuroides Nees. extracts on paracetamol induced hepatotoxicity in rats.

Pak J Pharm Sci 2020 Jul;33(4(Supplementary)):1899-1906

Department of Pharmaceutical Sciences, Dow College of Pharmacy, Dow University of Health Sciences, Karachi, Pakistan.

Aim of this study to evaluate the safety profile, hepatoprotective and in-vivo antioxidant activities of Dicliptera bupleuroides Nees. Toxicity studies were conducted in human RBCs and DNA by using standard procedures. Acute hepatoprotective investigation was carried out in albino rats by treated with all six fractions of D. bupleuroides 350 mg/kg/day. ALT, AST, ALP and total bilirubin (TB) were performed. The n-hexane fraction (200 mg/kg/day) exhibited appropriate hepatoprotective activity hence subjected to chronic study (14 days). Paracetamol induced the hepatotoxicity (350mg/kg) and silymarin (50 mg/kg) was standard drug. Liver function tests, liver peroxidation tests and histopathological examination were performed at the end. Hexane fraction showed significant decrease in the level of ALT (88.1±7.8), AST (93.8±7.6), ALP (136.3±8.4) and TB (0.6±0.03) as compared to the standard drug (p>0.05). Rats treated with ethyl acetate fraction showed decrease in MDA (42.8±0.7) while GSH was found to be increased (107.7±1.8) against the toxic group (51.3±2.9), (73.6±4.0) respectively. All the drug extracts decreased the oxidative stress and protect the DNA from free hydroxyl radicals. DNA damage protection activity of these fractions is due to phytochemicals present in these fractions. These results indicate that the plant fractions possess significant hepatoprotective and antioxidant activities with no toxic effects.
View Article and Find Full Text PDF

Download full-text PDF

Source
July 2020

Distinctive Microbial Signatures and Gut-Brain Crosstalk in Pediatric Patients with Coeliac Disease and Type 1 Diabetes Mellitus.

Int J Mol Sci 2021 02 3;22(4). Epub 2021 Feb 3.

Division of Gastroenterology, Hepatology, and Nutrition, Sidra Medicine, Doha 26999, Qatar.

Coeliac disease (CD) and Type 1 diabetes mellitus (T1DM) are immune-mediated diseases. Emerging evidence suggests that dysbiosis in the gut microbiome plays a role in the pathogenesis of both diseases and may also be associated with the development of neuropathy. The primary goal in this cross-sectional pilot study was to identify whether there are distinct gut microbiota alterations in children with CD ( = 19), T1DM ( = 18) and both CD and T1DM ( = 9) compared to healthy controls ( = 12). Our second goal was to explore the relationship between neuropathy (corneal nerve fiber damage) and the gut microbiome composition. Microbiota composition was determined by 16S rRNA gene sequencing. Corneal confocal microscopy was used to determine nerve fiber damage. There was a significant difference in the overall microbial diversity between the four groups with healthy controls having a greater microbial diversity as compared to the patients. The abundance of pathogenic proteobacteria and were significantly higher in CD patients. Differential abundance analysis showed that several bacterial amplicon sequence variants (ASVs) distinguished CD from T1DM. The tissue transglutaminase antibody correlated significantly with a decrease in gut microbial diversity. Furthermore, the Bacteroidetes phylum, specifically the genus was significantly correlated with corneal nerve fiber loss in the subjects with neuropathic damage belonging to the diseased groups. We conclude that disease-specific gut microbial features traceable down to the ASV level distinguish children with CD from T1DM and specific gut microbial signatures may be associated with small fiber neuropathy. Further research on the mechanisms linking altered microbial diversity with neuropathy are warranted.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/ijms22041511DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7913584PMC
February 2021

Virome-wide serological profiling reveals association of herpesviruses with obesity.

Sci Rep 2021 Jan 28;11(1):2562. Epub 2021 Jan 28.

Research Branch, Sidra Medicine, Doha, Qatar.

The relationship between viral infection and obesity has been known for several decades but epidemiological data is limited to only a few viral pathogens. The association between obesity and a wide range of viruses was assessed using VirScan, a pan-viral serological profiling tool. Serum specimens from 457 Qatari adults (lean = 184; obese = 273) and 231 Qatari children (lean = 111; obese = 120) were analyzed by VirScan. Associations with obesity were determined by odds ratio (OR) and Fisher's test (p values), and by multivariate regression analysis to adjust for age and gender. Although there was no association of viral infections with obesity in the pediatric population, a nominal association of obesity with seropositivity to members of the Herpesviridae family is observed for the adult population (OR = 1.5-3.3; p < 0.05). After adjusting p values for multiple comparisons (Bonferroni correction) the odds of being obese is significantly higher in herpes simplex virus 1 (HSV-1) seropositive Qatari adults (OR = 3.3; 95% CI 2.15-4.99; p = 2.787E - 08). By VirScan, the sero-prevalence of HSV1 is 81.3% and 57.1% among Qatari obese and lean adult populations, respectively. Higher prevalence of antibodies against several peptide epitopes of HSV-1/2 is positively associated with obesity (OR = 2.35-3.82; p ≤ 3.981E - 05). By multivariate regression analysis, HSV-1 was independently associated with obesity irrespective of age and gender. Our results suggest that obesity among Qataris may be associated with a higher prevalence of herpesvirus infections, in particular HSV-1. Furthermore, the high prevalence of antibodies against peptide antigens specific to HSV-1 and -2 in the obese population suggests that these viral peptides may play a role in adipogenesis. Further studies with these candidate peptides in cell culture or animal models may confirm their adipogenic roles.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41598-021-82213-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7843976PMC
January 2021

Aberrant development of pancreatic beta cells derived from human iPSCs with FOXA2 deficiency.

Cell Death Dis 2021 01 20;12(1):103. Epub 2021 Jan 20.

Diabetes Research Center, Qatar Biomedical Research Institute (QBRI), Hamad Bin Khalifa University (HBKU), Qatar Foundation (QF), PO Box 34110, Doha, Qatar.

FOXA2 has been identified as an essential factor for pancreas development and emerging evidence supports an association between FOXA2 and diabetes. Although the role of FOXA2 during pancreatic development is well-studied in animal models, its role during human islet cell development remains unclear. Here, we generated induced pluripotent stem cells (iPSCs) from a patient with FOXA2 haploinsufficiency (FOXA2 iPSCs) followed by beta-cell differentiation to understand the role of FOXA2 during pancreatic beta-cell development. Our results showed that FOXA2 haploinsufficiency resulted in aberrant expression of genes essential for the differentiation and proper functioning of beta cells. At pancreatic progenitor (PP2) and endocrine progenitor (EPs) stages, transcriptome analysis showed downregulation in genes associated with pancreatic development and diabetes and upregulation in genes associated with nervous system development and WNT signaling pathway. Knockout of FOXA2 in control iPSCs (FOXA2 iPSCs) led to severe phenotypes in EPs and beta-cell stages. The expression of NGN3 and its downstream targets at EPs as well as INSUILIN and GLUCAGON at the beta-cell stage, were almost absent in the cells derived from FOXA2 iPSCs. These findings indicate that FOXA2 is crucial for human pancreatic endocrine development and its defect may lead to diabetes based on FOXA2 dosage.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41419-021-03390-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7817686PMC
January 2021

Foliar exposure of zinc oxide nanoparticles improved the growth of wheat (Triticum aestivum L.) and decreased cadmium concentration in grains under simultaneous Cd and water deficient stress.

Ecotoxicol Environ Saf 2021 Jan 24;208:111627. Epub 2020 Nov 24.

Department of Environmental Sciences and Engineering, Government College University, 38000 Faisalabad, Pakistan; Department of Biological Sciences and Technology, China Medical University, Taichung 40402, Taiwan. Electronic address:

A pot study was conducted to explore the effectiveness of zinc oxide nanoparticles (ZnO NPs) foliar exposure on growth and development of wheat, zinc (Zn) and cadmium (Cd) uptake in Cd-contaminated soil under various moisture conditions. Four different levels (0, 25, 50, 100 mg/L) of these NPs were foliar-applied at different time periods during the growth of wheat. Two soil moisture regimes (70% and 35% of water holding capacity) were maintained from 6 weeks of germination till plant harvesting. The results revealed that the growth of wheat increased with ZnO NPs treatments. The best results were found in 100 mg/L ZnO NPs under normal moisture level. The lowest Cd and highest Zn concentrations were also examined when 100 mg/L NPs were applied without water deficit stress. In grain, Cd concentrations decreased by 26%, 81% and 87% in normal moisture while in water deficit conditions, the Cd concentrations decreased by 35%, 66% and 81% compared to control treatment when ZnO NPs were used at 25, 50 and 100 mg/L. The foliar exposure of ZnO NPs boosted up the leaf chlorophyll contents and also decreased the oxidative stress and enhanced the leaf superoxide dismutase and peroxidase activities than the control. It can be suggested that foliar use of ZnO NPs might be an efficient way for increasing wheat growth and yield with maximum Zn and minimum Cd contents under drought stress while decreasing the chances of NPs movement to other environmental compartment which may be possible in soil applied NPs.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ecoenv.2020.111627DOI Listing
January 2021

Phosphatidylinositol 4-kinase β mutations cause nonsyndromic sensorineural deafness and inner ear malformation.

J Genet Genomics 2020 10 28;47(10):618-626. Epub 2020 Oct 28.

Experimental and Clinical Research Center (ECRC), A Joint Cooperation Between the Charité Medical Faculty and the Max-Delbrueck-Center for Molecular Medicine in the Helmholtz Association (MDC), Lindenberger Weg.80, Berlin, 13125, Germany. Electronic address:

Congenital hearing loss is a common disorder worldwide. Heterogeneous gene variation accounts for approximately 20-25% of such patients. We investigated a five-generation Chinese family with autosomal-dominant nonsyndromic sensorineural hearing loss (SNHL). No wave was detected in the pure-tone audiometry, and the auditory brainstem response was absent in all patients. Computed tomography of the patients, as well as of two sporadic SNHL cases, showed bilateral inner ear anomaly, cochlear maldevelopment, absence of the osseous spiral lamina, and an enlarged vestibular aqueduct. Such findings were absent in nonaffected persons. We used linkage analysis and exome sequencing and uncovered a heterozygous missense mutation in the PI4KB gene (p.Gln121Arg) encoding phosphatidylinositol 4-kinase β (PI4KB) from the patients in this family. In addition, 3 missense PI4KB (p.Val434Gly, p.Glu667Lys, and p.Met739Arg) mutations were identified in five patients with nonsyndromic SNHL from 57 sporadic cases. No such mutations were present within 600 Chinese controls, the 1000 genome project, gnomAD, or similar databases. Depleting pi4kb mRNA expression in zebrafish caused inner ear abnormalities and audiosensory impairment, mimicking the patient phenotypes. Moreover, overexpression of 4 human missense PI4KB mutant mRNAs in zebrafish embryos resulted in impaired hearing function, suggesting dominant-negative effects. Taken together, our results reveal that PI4KB mutations can cause SNHL and inner ear malformation. PI4KB should be included in neonatal deafness screening.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jgg.2020.07.008DOI Listing
October 2020

Quantitative structure activity relationship studies of novel hydrazone derivatives as α-amylase inhibitors with index of ideality of correlation.

J Biomol Struct Dyn 2020 Dec 24:1-22. Epub 2020 Dec 24.

Department of Applied Sciences and Humanities, Mewat Engineering College, Nuh, India.

The present manuscript describes the synthesis, -amylase inhibition, studies and in-depth quantitative structure-activity relationship (QSAR) of a library of aroyl hydrazones based on benzothiazole skeleton. All the compounds of the developed library are characterized by various spectral techniques. -Amylase inhibitory potential of all compounds has been explored, where compound exhibits remarkable -amylase inhibition of 87.5% at 50 µg/mL. Robust QSAR models are made by using the balance of correlation method in CORAL software. The chemical structures at different concentration with optimal descriptors are represented by SMILES. A data set of 66 SMILES of 22 hydrazones at three distinct concentrations are prepared. The significance of the index of ideality of correlation (IIC) with applicability domain (AD) is also studied at depth. A QSAR model with best  = 0.8587 for split 1 is considered as a leading model. The outliers and promoters of increase and decrease of endpoint are also extracted. The binding modes of the most active compound, that is, in the active site of α-amylase () are also explored by molecular docking studies. Compound displays high resemblance in binding mode and pose with the standard drug acarbose. Molecular dynamics simulations performed on protein-ligand complex for 100 ns, the protein gets stabilised after 20 ns and remained below 2 Å for the remaining simulation. Moreover, the deviation observed in RMSF during simulation for each amino acid residue with respect to Cα carbon atom is insignificant.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/07391102.2020.1863861DOI Listing
December 2020

Somatostatin analogues for the treatment of hyperinsulinaemic hypoglycaemia.

Ther Adv Endocrinol Metab 2020 2;11:2042018820965068. Epub 2020 Dec 2.

Professor of Paediatrics, Weill Cornell Medicine-Qatar, Division Chief - Endocrinology, Department of Paediatric Medicine, Division of Endocrinology, Sidra Medicine, OPC, C6-340 |PO Box 26999, Al Luqta Street, Education City North Campus, Doha, Qatar.

Hyperinsulinaemic hypoglycaemia (HH) is a biochemical finding of low blood glucose levels due to the dysregulation of insulin secretion from pancreatic β-cells. Under normal physiological conditions, glucose metabolism is coupled to β-cell insulin secretion so that blood glucose levels are maintained within the physiological range of 3.5-5.5 mmol/L. However, in HH this coupling of glucose metabolism to insulin secretion is perturbed so that insulin secretion becomes unregulated. HH typically occurs in the neonatal, infancy and childhood periods and can be due to many different causes. Adults can also present with HH but the causes in adults tend to be different. Somatostatin (SST) is a peptide hormone that is released by the delta cells (δ-cells) in the pancreas. It binds to G protein-coupled SST receptors to regulate a variety of location-specific and selective functions such as hormone inhibition, neurotransmission and cell proliferation. SST plays a potent role in the regulation of both insulin and glucagon secretion in response to changes in glucose levels by negative feedback mechanism. The half-life of SST is only 1-3 min due to quick degradation by peptidases in plasma and tissues. Thus, a direct continuous intravenous or subcutaneous infusion is required to achieve the therapeutic effect. These limitations prompted the discovery of SST analogues such as octreotide and lanreotide, which have longer half-lives and therefore can be administered as injections. SST analogues are used to treat different forms of HH in children and adults and therapeutic effect is achieved by suppressing insulin secretion from pancreatic β-cells by complex mechanisms. These treatments are associated with several side effects, especially in the newborn period, with necrotizing enterocolitis being the most serious side effect and hence SS analogues should be used with extreme caution in this age group.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1177/2042018820965068DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7720331PMC
December 2020

Tracheal Stenosis after Tracheostomy.

Br J Oral Maxillofac Surg 2021 01 19;59(1):82-85. Epub 2020 Aug 19.

Maxillofacial Surgery, Queen Elizabeth Hospital, Birmingham, B15 2TH.

Introduction: Tracheal stenosis is a late and usually non-life threatening complication of surgical and percutaneous tracheostomies (PDT) as well as delayed endotracheal extubation.

Methods: We undertook a retrospective review of all patients who underwent a surgical tracheostomy over a 10 year period. Patients were included in the study if they had CT or MRI imaging of the tracheostomy site both pre-operatively and six or more weeks post operatively. Patients whose imaging was not available were excluded (n = 3) as were those patients who still had a tracheostomy in situ (n = 8). In total 91 patients were included in the study. In the same period 1170 surgical tracheostomies were performed by the maxillofacial surgeons. The images were analysed by a radiologist and the degree of stenosis reported.

Results: All 91 patients underwent a tracheostomy with a window. 83 patients did not demonstrate any stenosis. Looking at the remaining 8 patients with stenosis: 6 patients had stenosis of less than 25%, 1 patient had stenosis between 25-50% and 1 patient had stenosis greater than 50%. Both patients with stenosis greater than 25% had more than one surgical tracheostomy.

Conculsion: We have shown that the risk of stenosis is 8.8%, lower than often quoted in literature, and when it occurs it is likely to be symptomatic only in severe stenosis. Our main risk of stenosis was repeat surgical tracheostomies which also seems to be linked to a greater degree of stenosis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.bjoms.2020.08.036DOI Listing
January 2021

Use of the medial canthal point (MCP) as a reliable anatomical landmark to the frontal sinus.

Laryngoscope Investig Otolaryngol 2020 Oct 19;5(5):791-795. Epub 2020 Sep 19.

Department of Otolaryngology, Queen Elizabeth Hospital University Hospitals Birmingham NHS Foundation Trust Birmingham UK.

Objectives: Frontal sinus surgery is considered one of the more challenging aspects of Functional Endoscopic Sinus Surgery, due to the complex variations in normal sinus anatomy but also increased morbidity due to the close proximity of critical structures such as the anterior cranial fossa and orbits. We aim to investigate the medial canthal point (MCP) as an anatomical landmark for safe frontal sinus access.

Methods: The MCP intranasally is identified during surgery with non-tooth forceps, with one limb just anterior to the medial canthus and the other intranasally in the same coronal plane along the skull base. This point was identified on 100 paranasal sinus computed tomography (CT) scan reconstructions. The distance between the anterior cranial fossa and MCP was measured on imaging-medial canthal point distance (MCPD). The maximal anterior-posterior (AP) distance was measured on all scans.

Results: The average MCPD for males was 13.0 mm (8.7-20.4 mm) and for females 12.0 mm (6.8-22.8 mm). Mean AP distance for males was 12.0 mm (4.5-20.2 mm) and for females 10.4 mm (3.8-15.9 mm). Mean distance for all 100 patients was 12.6 mm (range 7.5-22.8 mm). In all cases, the MCP was anterior to the cranial fossa. Mixed effects modelling analysis showed a significant correlation between the MCPD and AP distance ( = .006).

Conclusion: The MCP is a consistent anatomical landmark that can serve as an adjunct to safe frontal sinus access alongside the first olfactory fiber and CT navigation systems. However, patient selection continues to be very important, with larger well pneumatized frontal sinuses being ideal to tackle earlier in a surgeon's career.

Level Of Evidence: NA.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/lio2.440DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7585238PMC
October 2020

Altered Serum Amino Acid and Acylcarnitine Profiles in Hyperinsulinemic Hypoglycemia and Ketotic Hypoglycemia.

Front Endocrinol (Lausanne) 2020 8;11:577373. Epub 2020 Oct 8.

Department of Pediatric Endocrinology and Inherited Metabolic Diseases, Children's Hospital of Fudan University, Shanghai, China.

Background: In addition to inborn metabolic disorders, altered metabolic profiles were reported to be associated with the risk and prognosis of some non-metabolic diseases, while as a rare metabolic disease, the overall secondary metabolic spectrum in congenital hyperinsulinemic hypoglycemia (HH) is largely undetermined. Therefore, we investigated metabolic profiles in HH patients and used ketotic hypoglycemia (KH) patients as a control cohort to unveil their distinct metabolic features.

Methods: A total of 97 hypoglycemia children, including 74 with hyperinsulinemic hypoglycemia and 23 with ketotic hypoglycemia, and 170 euglycemia control subjects were studied retrospectively. Clinical and biochemical data were collected. The normoglycemic spectra of amino acids and acylcarnitines were determined by liquid chromatography tandem mass spectrometry. The serum insulin and fatty acid concentrations during standardized fasting tests in hypoglycemia patients were also collected. Receiver operating characteristic curve analysis was performed to screen potential biomarkers.

Results: Among the normoglycemic spectra of amino acids, blood valine ( < 0.001), arginine ( < 0.001), threonine ( = 0.001), glutamate ( = 0.002), methionine ( = 0.005), ornithine ( = 0.008), leucine ( = 0.014), alanine ( = 0.017), proline ( = 0.031), citrulline ( = 0.042), aspartate ( = 0.046), and glycine ( = 0.048) levels differed significantly among the three groups. Significantly decreased levels of long- (C14:1, < 0.001; C18, < 0.001), medium- (C8, < 0.001; C10, < 0.001; C10:1, < 0.001), and short-chain (C4-OH, < 0.001; C5OH, < 0.001) acylcarnitines were found in the hyperinsulinemic hypoglycemia group. Hyperinsulinemic hypoglycemia children with focal lesions and diffuse lesions had similar amino acid and acylcarnitine spectra. C10:1 < 0.09 μmol/L, threonine > 35 μmol/L, and threonine/C10:1 > 440 showed sensitivities of 81.1, 66.2, and 81.1% and specificities of 72.7, 78.3, and 81.8%, respectively, in distinguishing HH from KH.

Conclusions: We found significantly different altered serum amino acid and acylcarnitine profiles at normoglycemia, especially decreased C10:1 and increased threonine levels, between HH and KH children, which may reflect the insulin ketogenesis inhibition effect in HH patients; however, the detailed mechanisms and physiological roles remain to be studied in the future.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fendo.2020.577373DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7579424PMC
June 2021

Psychological Impairment and Coping Strategies During the COVID-19 Pandemic Among Students in Pakistan: A Cross-Sectional Analysis.

Disaster Med Public Health Prep 2020 Oct 22:1-7. Epub 2020 Oct 22.

Department of Clinical Pharmacy, College of Pharmacy, Jouf University, Sakaka, Al-Jouf, Kingdom of Saudi Arabia.

High levels of stress are expected when crises affect people's lives. Therefore, this Web-based, cross-sectional study was conducted among university students from Pakistan to investigate the psychological impairment and coping strategies during the coronavirus disease 2019 (COVID-19) pandemic. Google Forms were used to disseminate the online questionnaire to assess anxiety (Generalized Anxiety Disorder-7), depression (Patient Health Questionnaire-9), and coping strategies (Brief-COPE). A total of 1134 responses (age, 21.7 ± 3.5 y) were included. The frequency of students having moderate-severe anxiety and depression (score ≥ 10) were ≈ 34% and 45%, respectively. The respondents' aged ≥ 31 y had significantly lower depression score than those ≤ 20 y (P = 0.047). Males had significantly less anxiety (6.62 ± 5.70 vs 7.84 ± 5.60; P = 0.001) and depression (8.73 ± 6.84 vs 9.71 ± 7.06; P = 0.031) scores. Those having family members, friends, or acquaintances infected with disease had significantly higher anxiety scores (8.89 ± 5.74 vs 7.09 ± 5.56; P < 0.001). Regarding coping strategies, the majority of respondents were found to have adopted religious/spiritual coping (6.45 ± 1.68) followed by acceptance (5.58 ± 1.65), self-distraction (4.97 ± 1.61), and active coping (4.81 ± 1.57). In conclusion, COVID-19 caused significant impairment on mental health of the students. The most frequent coping strategies adopted by students were religious/spiritual and acceptance coping. During epidemics, mental health of students should not be neglected.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1017/dmp.2020.397DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7873451PMC
October 2020

Asphodelus tenuifolius extracts arrested inflammation and arthritis through modulation of TNF-α, NF-κB, ILs, and COX-2 activities in in vivo models.

Inflammopharmacology 2021 Apr 16;29(2):483-497. Epub 2020 Oct 16.

Faculty of Pharmaceutical Sciences, Government College University Faisalabad, Faisalabad, Punjab, Pakistan.

Asphodelus tenuifolius is traditionally used in the management of rheumatic pain and inflamed body parts. The current study validated its traditional use as an anti-arthritic and anti-inflammatory agent using a series of in vivo models. Carrageenan and histamine-induced acute oedema models were employed to study the effects of n-hexane (n-HeAT) and ethanolic (EeAT) extracts on acute inflammatory mediators and were found to inhibit oedema formation in a dose-dependent manner. Formalin and complete Freund's adjuvant (CFA) were injected into the hind paw of rats for the induction of arthritis. In the formalin model both n-HeAT and EeAT showed significantly better (p < 0.05) anti-oedema effects from day 6 onward. In CFA model rats were treated on 8th day of induction with extracts at the doses of 250, 500, and 750 mg/kg respectively. Piroxicam (10 mg/kg) and normal saline (10 mL/kg) were used as positive and negative controls respectively. Both n-HeAT and EeAT significantly (p < 0.05) decreased arthritis development in a time-dependent manner and at 28th day extent of inflammation was even less than that observed at day 8. The arthritic score was measured at day 12, 16, 20, 24, and 28 and was observed to be significantly less (p < 0.05) in animals treated with 750 mg/kg of n-HeAT and EeAT, respectively. Joint inflammation (p < 0.01), bone erosion (p < 0.001) and, pannus formation (p < 0.01) were significantly declined in A. tenuifolius treatment groups. Radiographic evaluations (X-ray) were conducted to check bone integrity and extent of inflammation and were observed to be diminished at day 28 in A. tenuifolius extracts treated groups. HPLC was performed to screen the phytochemical profile of n-HeAT and EeAT and were found to contain flavonoids and phenolic compounds. Quantitative real-time polymerase chain reaction (qPCR) was performed to detect effects of n-HeAT and EeAT treatments on inflammatory markers i.e., IL-4, IL-6, IL-10, COX-2, NF-κB, and I-κB using blood samples. ELISA assays were performed for the detection of levels of C-reactive proteins, respectively. Significant downregulation of TNF-α, IL-4, IL-6, IL-1β, COX-2, NF-κB with simultaneous upregulation of IL-10 and I-κB was observed in n-HeAT and EeAT treatment groups. ELISA assays also showed significant (p < 0.05) down-modulation in the serum levels of CRP and TNF-α. Both extracts showed relatively weak antioxidant activities as compared with ascorbic acid in in vitro assay. Based on findings of the current study it is concluded that A. tenuifolius has anti-inflammatory and anti-arthritic effects and thus has potential to be used as an adjunct to standard NSAIDs therapy.Graphic abstract.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s10787-020-00761-zDOI Listing
April 2021

One-year experience of hybrid closed-loop system in children and adolescents with type 1 diabetes previously treated with multiple daily injections: drivers to successful outcomes.

Acta Diabetol 2021 Feb 12;58(2):207-213. Epub 2020 Oct 12.

Division of Endocrinology and Diabetes, Department of Pediatric Medicine, Sidra Medicine, HB 6E 219, Al Luqta Street, Education City North Campus, PO Box 26999, Doha, Qatar.

Objective: To evaluate the effect of a 1-year hybrid closed-loop (HCL) system on glycemic control in children and adolescents with type 1 diabetes (T1D) previously treated with multiple daily injections (MDI).

Methods: This was a 1-year observational study, as a continuation of the previous 3 months prospective study of pediatric patients with T1D conducted at Sidra Medicine in Qatar. The study enrolled individuals aged 7-18 years with T1D > 1 year, on MDI with self-monitoring of blood glucose or continuous glucose monitoring, with no prior pump experience, and with an HbA1c level < 12.5% (< 113 mmol/mol). After the first 3 months of HCL use, patients were followed at 6, 9 and 12 months, where HbA1c was obtained and pump data were collected.

Results: All 30 participants (age 10.24 ± 2.6 years) who initiated HCL completed 12 months of HCL system use in Auto Mode. The participants used the sensor 88.4 ± 6.5% of the time with Auto Mode usage 85.6 ± 7.4% during 12 months of HCL system use. HbA1c decreased from 8.2 ± 1.4% (66 ± 15.3 mmol/mol) at baseline, to 6.7 ± 0.5% (50 ± 5.5 mmol/mol) at 3 months (p = 0.02) and remained stable to 7.1 ± 0.6 (54 ± 6.6 mmol/mol) at 12 months (p = 0.02). TIR (70-180 mg/dL) increased from 46.9% at baseline to 71.9% at 1 month and remained above 70% during the 12 months of HCL use.

Conclusion: HCL system (MiniMed 670G) in children and adolescents previously treated with MDI significantly improves glycemic outcomes (HbA1c and Time in Ranges) immediately during the first month. This improved glycemic control was maintained over the 1 year following Auto Mode initiation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00592-020-01607-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7548407PMC
February 2021

Generation of two human iPSC lines from patients with maturity-onset diabetes of the young type 2 (MODY2) and permanent neonatal diabetes due to mutations in the GCK gene.

Stem Cell Res 2020 10 13;48:101991. Epub 2020 Sep 13.

College of Health and Life Sciences, Hamad Bin Khalifa University (HBKU), Qatar Foundation (QF), Education City, Doha, Qatar; Diabetes Research Center, Qatar Biomedical Research Institute (QBRI), Hamad Bin Khalifa, University (HBKU), Qatar Foundation (QF), Education City, PO Box 34110, Doha, Qatar. Electronic address:

Heterozygous and homozygous mutations in the glucokinase (GCK) gene leads to maturity-onset diabetes of the young type 2 (MODY2) and permanent neonatal diabetes (PNDM), respectively. Here, we report the generation of two induced pluripotent stem cell (iPSC) lines, QBRIi010-A and QBRIi011-A, from patients with MODY2 and PNDM due to mutations in the GCK gene (c.437 T > C). The generated iPSC lines displayed pluripotency characteristics, were able to differentiate into the three germ layers, and showed normal karyotypes. These iPSC lines will serve as valuable human cell models for understanding diabetes pathogenesis and developing new therpaies for diabetes.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.scr.2020.101991DOI Listing
October 2020

Corneal confocal microscopy demonstrates minimal evidence of distal neuropathy in children with celiac disease.

PLoS One 2020 21;15(9):e0238859. Epub 2020 Sep 21.

Division of Gastroenterology, Hepatology, and Nutrition, Sidra Medicine, Doha, Qatar.

Objectives: The aim of this study was to utilise corneal confocal microscopy to quantify corneal nerve morphology and establish the presence of sub-clinical small fibre damage and peripheral neuropathy in children with celiac disease.

Methods: This is a cross-sectional cohort study of twenty children with celiac disease and 20 healthy controls who underwent clinical and laboratory assessments and corneal confocal microscopy. Corneal nerve fiber density (no.mm2), corneal nerve branch density (no.mm2), corneal nerve fiber length (mm.mm2), corneal nerve fiber tortuosity and inferior whorl length (mm.mm2) were quantified manually.

Results: Corneal nerve fiber density (34.7±8.6 vs. 32.9±8.6; P = 0.5), corneal nerve branch density (47.2±24.5 vs. 47.3±20.0; P = 0.1) and corneal nerve fiber length (20.0±5.1 vs. 19.5±4.5; P = 0.8) did not differ between children with celiac disease and healthy controls. Corneal nerve fiber tortuosity (11.4±1.9 vs 13.5±3.0; P = 0.01) was significantly lower and inferior whorl length (20.0±5.5 vs 23.0±3.8; P = 0.06) showed a non-significant reduction in children with celiac disease compared to healthy controls. Inferior whorl length correlated significantly with corneal nerve fiber density (P = 0.005), corneal nerve branch density (P = 0.04), and corneal nerve fiber length (P = 0.002).

Conclusion: Corneal confocal microscopy demonstrates minimal evidence of neuropathy in children with celiac disease.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0238859PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7505458PMC
November 2020
-->