01/10/2023
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مريم أمين ساب مجلي

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
مريم أمين ساب مجلي
دكتوراه
الطب والخدمات الصحية
Loughborough University

مجال
التميز

تميز دراسي وبحثي

 

 

البحوث المنشورة

 

البحث (1):

 

عنوان البحث:

ROLE OF TAURINE IN
DIABETES AND DIABETES COMPLICATIONS

رابط البحث:

Link

تاريخ النشر:

July
2010

موجز عن البحث:

Taurine
(2-amino-ethane sulfonic acid) is a free semi-essential amino acid derived
from cysteine and methionine. It is not incorporated in proteins, but it is
found free in many tissues, and it is found in the plasma at concentration of
about 50 μmol/L. Many studies suggest that diabetic patient have low levels
of taurine and strongly advise that taurine could have beneficial effects for
diabetic patients. Our study included 130 subjects divided into four groups,
group I included 27 patients with T1DM, group II included 28 patients with
T2DM, group III included 45 patients with T2DM with CVD which was
characterized by hypercholesterolemia and hypertension and group IV included
30 age matching healthy subjects control group. Blood samples were collected
after overnight fasting (8-10 hours) and divided into three portions. Blood
samples were used for determining HbA1c. Serum and plasma samples were a
liquoted and kept at -30°C for biochemical investigations. Sera were used for
the determination of glucose, cholesterol, TAG, LDL,HDL, uric acid and
insulin levels as a routine in the hospital laboratory. Also, serum samples
were used for the determination of total thiol and NO levels. Plasma samples
were used for malondialdehyde and taurine determination. The results of this
study showed a significant decrease in taurine in group II and an
insignificant increase in group I and III. The level of thiol, insulin, uric
acid and NO showed a significant increase in all the studied groups. HDL and
TAG serum levels showed a non significant increase in all the studied groups.
While LDL showed a significant increase in all the studied groups. Appositive
correlation was found between LDL and cholesterol in T1DM and T2DM with CVD
and in control groups while, LDL showed a positive correlation with HDL in
T2DM patients groups. Finally the results of our study give evidences on the
importance of taurine. Our study recommended further future studies on Saudi
diabetic patients, concerning the availability of giving taurine as a food
supplement to those group of patients. Hoping that taurine may decrease
suffering from diabetes complications specially CVD.

 

 

المؤتمرات العلمية:

 

المؤتمر (1):

 

عنوان المؤتمر:

The
Sixth Saudi International Conference (SIC2012)

تاريخ الإنعقاد:

October
2012

بلد
ومكان الإنعقاد:

Brunel
University, UK

طبيعة المشاركة:

عرض
ورقة علمية و ملصق

عنوان المشاركة

DNA
binding studies of fluorinated active compounds

موجز عن المشاركة

Introduction:

Heterocyclic
chemistry is very popular during lead optimization in drug discovery and
development in the pharmaceutical industry, and the
majority of the therapeutic agents contain at least one heterocyclic sub-unit
within their chemical structure. The development of synthetic organo-fluorine
chemistry and the proper understanding of the role of fluorine in biological
behaviors of the compounds have been facilitated to synthesis more effective
pharmaceutical candidates (Cartwright et al. 2010). Fluorinated compounds are
frequently used in the pharmaceutical industry and it has been estimated that
worldwide approximately 20-25 % of all drugs contain at least one fluorine
atom (Ko et al. 2011). The present study aimed to synthesis of novel
fluorinated heterocyclic active compounds. In addition identify the biological
activity of the synthesised compounds as anti-tumour agents using DNA thermal
denaturation method with U.V absorption at 260 nm.

DNA
thermal denaturation assay:

DNA
thermal denaturation refers to the heat treatment over a critical temperature
leading to denaturation of DNA double helix into single strands component in
the presence and absence of the drug.

The
temperature at which half of the DNA is denatured called melting temperature
(Tm) (Palchaudhuri & Hergenrother 2007).

ACTD was used to
determine the Tm value of a known strong DNA intercalating agent.

Results
and discussion:

Three novel
fluorinated compounds have been synthesized and fully characterized by NMR,
IR spectroscopy, mass spectrum and elemental analysis.

 

 

المؤتمر (2):

 

عنوان المؤتمر:

The
Fifth Saudi International Conference (SIC2011)

تاريخ الإنعقاد:

June
2011

بلد
ومكان الإنعقاد:

University
of Warwick, Coventry, UK

طبيعة المشاركة:

عرض
ورقة علمية و ملصق

عنوان المشاركة

Investigation of co-medicants in the respiratory and inflammation therapy
area as inhibitors of the human OATP1B1 hepatic uptake transporter using in
vitro cell-based transport assays

موجز عن المشاركة

Introduction:

Transporters
are transmembrane carrier proteins that transport compounds across the
biological membranes. Additionally, they construct a defensive barrier to
toxicants by bringing their polarized excretion from the body.

Organic
Anion Transporting polypeptide 1B1 (OATP1B1) is a product of gene SLCO1B1 and
it is specifically expressed on the basolateral (sinusoidal) membrane of
human hepatocytes. Due to its liver-specific expression and its capacity for
transporting a large number of structurally different compounds, it has been
suggested that OATP1B1 plays an important role in hepatic drug uptake and
subsequently elimination.  Thus,
inhibition of OATP1B1 can alter the pharmacokinetics of OATP1B1 substrate
drugs causing clinically relevant drug-drug interactions.

In
this study 12 co-medicants Pravastatin (PV), Paracetamol (PC), Metformin
(MT), Warfarin (WR), Enalapril (EN), Salbutamol (SB), Budesonide (BD),
Erythromycin (ER), Cimetiden (CM), Furosemide (FD), Ibuprofen (IB),
Probenecid (PB) and Methotrexate (MX) were examined as inhibitors of
OATP1B1  transporter in vitro. Among
the 12 co-medicants investigated, 7 drugs exhibited inhibition of OATP1B1
activity and then there inhibition potential determined and their clinical
interactions were predicted.

Methods:

HEK293-OATP1B1
and HEK293-MOCK cell cultures:

The
cells are grown on cell culture flasks at 37C and they sub-cultured
depending on their density. The cells were cultured in 12-well plates and
prepared to the uptake assays1.

OATP1B1-
mediated uptake assays:

OATP1B1‑mediated
transport was determined by measuring uptake of [3H] estradiol
17β-glucuronide as a substrate into plated HEK293-OATP1B1 cells
(approximately 0.45 million cells/well using a 12-well plate) versus      HEK293-MOCK cells, at approximately
37C1. 

Spot
inhibition experiment:

To
determine the inhibition of OATP1B1-mediated transport the uptake of the
probe substrate [3H] estradiol 17β-glucuronide (1 µM) by HEK293-OATP1B1 and
HEK293-MOCK cells was determined in the absence or presence the co-medicants
(100 µM) or rifamycin SV (500 µM) was studied. 

Determination
of inhibition potential IC50 of co-medicants:

Uptake
of the probe substrate [3H] estradiol 17β-glucuronide by HEK293-OATP1B1 cells
was determined in the absence or the presence of a range of 6 concentrations
of co-medicants in order to determine apparent IC50 values for the inhibition
of OATP1B1-mediated transport. The IC50 were determined by curve-fitting
using XLfit 5.1

Result
and Discussion:

Screening
of co-medicants for OATP1B1 inhibition:

OATP1B1-mediated
uptake of [3H] estradiol 17β-glucuronide (1 µM) in HEK293-OATP1B1 cells and
HEK293-MOCK cells was studied in the presence and absence of co-medicants
(100 µM) and is shown in Figure 1. The passive transport of [3H] estradiol
17β-glucuronide in HEK293-MOCK cells was unchanged in the presence of
co-medicants but active transport due to OATP1B1 was inhibited by various
co-medicants to different levels.


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