QSAR analysis of sodium glucose co-transporter 2 (SGLT2) inhibitors for anti-hyperglycaemic lead development.

QSAR (Quantitative Structure Activity Relationship) modelling was performed on a dataset of 90 sodium-dependent glucose cotransporter 2 (SGLT2) inhibitors. The quantitative and explicative evaluations revealed some of the subtle and distinguished structural features that are responsible for the inhibitory potency of these compounds against SGLT2, such as less possible number of ring carbons at 8 Å from the lipophilic atoms in the molecule (fringClipo8A) and more possible value for the sum of the partial charges of the lipophilic atoms present within seven bonds from the donor atoms (lipo_don_7Bc). Multivariate GA-MLR (genetic algorithm-multi linear regression) and thorough validation methodology out-turned a statistically robust QSAR model with a very high predictability shown from various statistical parameters. A QSAR model with r2 = 0.83, F = 51.54, Q2LOO = 0.79, Q2LMO = 0.79, CCCcv = 0.88, Q2Fn = 0.76-0.81, r2ext = 0.77, CCCext = 0.85, and with RMSEtr < RMSEcv was proposed. This QSAR model will assist synthetic chemists in the development of the SGLT2 inhibitors as the antidiabetic leads.

Circulating micro RNA-223 and angiopoietin-like protein 8 as biomarkers of gestational diabetes mellitus.

BACKGROUND: Gestational diabetes mellitus (GDM) is a serious health problem associated with both foetal and maternal complications. New biomarkers that can predict or help in the early diagnosis of GDM are needed to minimize the hazards of hyperglycaemia in pregnant women and their offspring. We hypothesised a link between levels of microRNA-223 (miRNA-223) and Angiopoietin-Like Protein 8 (ANGPTL8) and GDM. MATERIALS AND METHODS: The study included 109 patients with confirmed early diagnosed GDM and 103 healthy control pregnant women in their second or third trimester. miRNA-223 and ANGPTL8 blood levels were assessed by real-time RT-PCR and sandwich ELISA, respectively, laboratory markers by standard methods. RESULTS: There was a significant increase in mean [SD] miRNA-223 and ANGPTL8 in GDM (0.31 [0.06] relative units) and (692 [199] pg/ml), respectively, in the GDM women compared to healthy pregnant women (0.17[0.05] relative units) and (261 [127] pg/ml), respectively, P  < 0.001. miRNA-223 and ANGPTL8 correlated significantly with each other (r = 0.38, P  < 0.001) and with fasting, 1-h and 2-h postprandial blood glucose levels (all P ≤ 0.002) HbA1 c (P  < 0.025), total cholesterol (P < 0.01), LDL-C and triglycerides (both P ≤ 0.005). The ROC area under curve (AUC) (95%CI) was 0.94 (0.91-0.97) for ANGPTL8, 0.92 (0.88-0.96) for miRNA-223 and 0.97 (0.95 - 0.99) for their combination. CONCLUSIONS: These findings support the hypothesis of involvement of both miRNA-223 and ANGPTL8 in the pathogenesis of GDM. The difference between levels in GDM patients and in control pregnant women indicates potential use for early diagnosis or prediction of GDM.

Holoprosencephaly spectrum among Egyptian patients: clinical and cytogenetic study.

We report 24 patients with holoprosencephaly (HPE) spectrum screened for Del 7q36 and subtelomere 13q. They were divided according to the type of HPE into: 6 alobar, 15 semilobar, 1 lobar and 2 middle interhemispheric variant (MIH). All patients presented with global developmental delay. Microcephaly was in 83.3% and midfacial developmental defects were in the form of; cyclopia, arrhinia and agnathia in 2 patients (8.3%), premaxillary agenesis in 2 patients (8.3%), cleft lip and palate in 7 patients (29.2%), hypotelorism in 8 patients (33.3%) and hypertelorism in 9 patients (37.5%). The neurological deficits were as follows: abnormal tone and spasticity were present in all of them with exceptional of a single patient with MIH who presented with hypotonia and was able to walk independently at the age of 3 years, athetoid and/or dystonic movements of limbs in 22 patients, seizures in twelve patients (50%) and abnormal EEG in 15 patients (62.5%). Poor temperature regulation was found in 50% of patients and diabetes insipidus was documented in 3 patients (12.5%). The MRI showed complete or partial fusion of basal ganglia and thalami in 21 patients (87.5%) and 19 patients (79.2%) respectively, fused mesencephalon in 8 patients (33.3%), incomplete separation of mesencephalon from diencephalon in 4 patients (16.7%), dorsal cyst in 10 patients (41.7%), abnormal gyral pattern anteriorly in 15 patients (62.5%), anterior located sylvian fissures in 22 patients (99.7%), complete or partial agenesis of the corpus callosum (ACC) in all patients and Dandy-Walker malformation (DWM) in three patients (12.5%). A small occipital cephalocele was detected clinically and radiological as atretic type in MIH patient. Karyotype analysis demonstrated 47, XY+13 in a patient with alobar holoprosencephaly, 46, XY,t(12;13) (q13q24.1;q14q33) in a semilobar case associated with DWM, 46, XY, del(13)(q34) in one semilobar case and three cases had del 7q36 using FISH technique in two semilobar cases and one lobar case. Conclusion: This study highlights the clinical spectrum in patients with HPE and report a case of HPE and DWM associated with t(12;13). Neuroimaging delineated the pathogenesis underlying developmental defects in HPE. Accurate molecular diagnosis is crucial for further understanding of the pathogenesis of HPE.

Clinical and hematological study for Parvovirus b19 infection in children with acute leukemia.

The role of Parvovirus B19 in acute leukemia is under debate. This study aimed to detect parvovirus B19 DNA together with its antibodies in the sera of children with recent acute leukemia and those with acute leukemia receiving chemotherapy to clarify the contribution of this infection to changes observed in hematological and clinical presentations in these populations. Two groups were included: Group I comprised 45 children with acute leukemia receiving chemotherapy and Group II comprised 40 children with recently diagnosed acute leukemia. Serum parvovirus B19 IgG and IgM were investigated by enzyme-linked immunosorbant assay and the virus DNA was sought by polymerase chain reaction assay. Viral DNA was found in 22.2% of Group I patients and in 45% of Group II patients. Hemoglobin levels were significantly reduced in patients with recent infection, accompanied by statistically significant lymphocytosis in Group I patients. Group II patients with recent infection had marked neutropenia with lymphocytosis and thrombocytopenia. There was statistically significant lymphadenopathy and hepatosplenomegaly in patients with recent infection in both groups. Parvovirus B19 infection is an important cause of cytopenia in children with acute leukemia both when recently diagnosed and receiving chemotherapy. This can affect the schedule of chemotherapy. Moreover, the presence of Parvovirus B19 is associated with marked lymphadenopathy and hepatosplenomegaly.

Head circumference reference data for Egyptian children and adolescents.

Data from a cross-sectional study of 27,826 healthy children in Cairo, Egypt, were used to construct standard growth charts of head circumference and reference values of relative head circumference to length/height for each sex. The sample was collected during the Egyptian Growth Curve Project for children and adolescents in 2002. Values were obtained for each month cohort for children aged 1-24 months, then for each year cohort until age 18 years. The values were compared with those of other populations. The constructed growth standards are suitable for growth monitoring programmes throughout Egypt.

Head circumference reference data for Egyptian children and adolescents

Data from a cross-sectional study of 27 826 healthy children in Cairo, Egypt, were used to construct standard growth charts of head circumference and reference values of relative head circumference to length/height for each sex. The sample was collected during the Egyptian Growth Curve Project for children and adolescents in 2002. Values were obtained for each month cohort for children aged 1-24 months, then for each year cohort until age 18 years. The values were compared with those of other populations. The constructed growth standards are suitable for growth monitoring programmes throughout Egypt

Synthesis of pyrido[2,1-c][1,2,4]triazine,1,2,4 triazolo[4,3-a] pyridine and 2-(substituted-pyrazolyl)nicotinonitrile and their effect on Biomphalaria alexandrina snail enzymes.

The reaction of 2-hydrazino-4-(4-methoxyphenyl)-6-pheny-nicotinonitrile 3 with halo compounds yielded 4a-c,5,6. Heating 3 with carbon disulphide gave 7-(4-methoxyphenyl)-5-phenyl-3-thioxo-2,3-dihydro [1,2,4-] triazolo [4,3-a] pyridine-8-carboxylic amide 7. The behaviour of 3 towards some alpha,beta-unsaturated nitriles ,ethoxymethylene and ketene dithioacetal derivatives has been investigated, affording 9a-c,11a-c,13a-c,16a,b respectively. The activity of compounds 4a,5,6 and 7 have been investigated as molluscicidal.

Facile synthesis of fused pyrazolo[1,5-a]pyrimidinepyrazolo [1,5-a]triazines and N-sulphonamidopyrazoles as antiinflammatory.

Interaction of hydrazine hydrate with methyl (2-E)-2-cyano-3-[(1,5-dimethyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazol-4-yl)amino]-3-(methylsulphanyl)-2-propenoate 2 which was obtained by the reaction of methyl-2-cyano-3,3-bis(methylsulphanyl) acrylate 1 with 4-amino-1-phenyl-2,3-dimethyl pyrazoline-5-one afforded methyl-5-amino-3-[(1,5-dimethyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazol-4-yl)amino]-1H-pyrazole-4-carboxylate 3a. The pyrazolin derivative 3a is a good precursor for the synthesis of pyrazolo[1,5-a]pyrimidines which is based on the interaction of 3a with alpha,beta-unsaturated nitrile derivatives. The biological effects of some of the newly synthesized compounds were also investigated as antiinflammatory, analgesic and antipyretic drugs. Compounds 2b, 4a, 3a, 3b, 2a and 4b were found to have significant antiinflammatory activity in descending order in comparison to control groups phenylbutazone. Compounds 3a, 2a, 4b, 4a, 2b and 3b have analgesic activity in decreasing order. Compound 3a was the most potent and had 82.6% potency of Novalgin. Compounds 2b, 2a, 3b, 4b, 3a and 4a were found to have significant antipyretic activity in descending order. Compounds 2a, 4b induced no ulcerogenic activity, while compounds 3b, 2b, 4a and 3a showed only slight ulcerogenic activity.

The reactions of diaminomaleonitrile with isocyanates and either aldehydes or ketones revisited.

A reinvestigation of the reactions of urea derivatives of diaminomaleonitrile 2 with aldehydes or ketones in the presence of triethylamine has established that the products of these reactions are not pyrimidino[5,4-d]pyrimidines 9 as previously reported, but 8-oxo-6-carboxamido-1,2-dihydropurines 12, which are oxidized rapidly in air to the corresponding 6-carboxamidopurines 13. Similarly, the reaction of Schiff base derivatives of DAMN 5 with isocyanates in the presence of triethylamine gives the substituted 2-oxoimidazoles 20 and not the pyrimidine derivatives 8 as previously claimed. The compounds 20 cyclize in solution and are easily oxidized to 8-oxopurine-6-carbonitriles 22, which give the same 8-oxopurine-6-carboxamides 13 upon further hydrolysis.

Digital and palmar dermatoglyphics of two Egyptian northern Sinai tribes.

Digital and palmar dermatoglyphics were analyzed in two northern Sinai tribes. The sample consists of 200 normal individuals (males and females), 100 from each tribe. The results were compared to urban Egyptians and some selected African tribes. A high degree of similarity was observed in most of dermatoglyphic traits between each tribe and the urban Egyptian sample. Certain quantitative dermatoglyphic traits of the two tribes showed a strong resemblance to those of African populations. These results may point to a common gene pool of the two tribes and the urban Egyptians. Moreover, the present study suggests some genetic admixture of the northern Sinai tribes with the neighboring African populations. The study emphasizes that the dermatoglyphic features are important biological elements that may prove or disprove the phenotypical and genotypical relationships between various populations in the different environments and geographical locations.