DNA ploidy analysis of borderline epithelial ovarian tumours

Objective: Borderline epithelial ovarian tumors not uncommonly pose a great difficulty to surgical pathologists as morphologically they may show very similar features as those of malignant epithelial tumors except invasion. However it is important to separate these from their invasive counterparts because of their superior prognosis. Recently, attention has been focussed on the prognostic value of flow cytometric analysis of DNA ploidy in borderline epithelial ovarian tumors. The purpose of this study is to investigate whether flow cytometric analysis of cellular DNA content acts as a useful adjunct to the histopathological diagnosis of borderline malignancy. Materials and Methods: Fifteen histologically confirmed borderline serous epithelial tumors of the ovary were selected. Samples were analyzed on a FACScan flow cytometer using the software MODFIT. A total of 10,000 nuclei were counted each time. Results: The mean CV for the 15 cases was 3.67 (Range 2.4-5.0). In the DNA histograms a diploid sample was defined as one that had a single Go/Cl peak. An aneuploid tumour was defined as one that displayed an additional distinct peak. All 15 cases of borderline serous epithelial tumors showed a diploid stemlinc with DNA index between 0.9-i .10 Conclusion: This study suggests that aneuploidy if ever demonstrated in histological confirmed borderline tumors should prompt extensive sampling of the tumor and a close follow up

Interactions of neomycin and calcium in synaptosomal membranes and polyphosphoinositide monolayers

Neomycin and related aminoglycosidic antibiotics displace calcium from synaptosomes of guinea pig cerebral cortex and from preparations of phosphatidylinositol diphosphate. At low drug concentrations, inhibition of synaptosomal calcium binding is competitive (Ki = 3[middle dot]10-5M), at high concentrations it is non-competitive (Ki = 4[middle dot]10-4M). Monomolecular films of phosphatidylinositol diphosphate are contracted by low concentrations of neomycin in the subphase, and are expanded at high concentrations. This expansion persists even at the collapse pressure indicating a strong interaction between the drug and the lipid.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/21792/1/0000187.pd

A Case report of rare disease Prolidase deficiency in a 15-year-old Pakistan boy

Case presentation Prolidase enzyme plays a crucial role in proline-rich proteins metabolism and physiological processes such as inflammation, cell proliferation, wound healing, angiogenesis, and carcinogenesis. Due to mutations in the peptidase D (PEPD) gene, the catalytic activity of prolidase loss results in prolidase deficiency. Deficiency of prolidase enzyme is an autosomal inborn metabolic rare genetic disorder that has neither any proper treatment nor consensus for treatment. With approximately 100 cases recorded worldwide, the submitted manuscript describes the 2nd recorded case of prolidase deficiency, an extremely uncommon autosomal recessive disorder associated with collagen metabolism, in a 15-year-old Pakistan boy. The disorder typically becomes apparent during infancy. Affected individuals may have enlargement of the spleen (splenomegaly); in some cases, both the spleen and liver are enlarged (hepatosplenomegaly). Diarrhea, vomiting, and dehydration may also occur. People with prolidase deficiency often develop skin lesions, especially on their hands, feet, lower legs, and face. The severity of the skin involvement, which usually begins during childhood, may range from a mild rash to severe skin ulcers. The severity of symptoms in prolidase deficiency varies greatly among affected individuals. Here we present the report of a 15-year-old boy who has all the clinical manifestations of deficiency of prolidase. This is the 2nd case in Pakistan's 229,488,994 million population

S-Alkylated/aralkylated 2-(1H-indol-3-yl-methyl)-1,3,4- oxadiazole-5-thiol derivatives. 2. Anti-bacterial, enzymeinhibitory and hemolytic activities

Purpose: To evaluate the antibacterial, enzyme-inhibitory and hemolytic activities of Salkylated/aralkylated 2-(1H-indol-3-ylmethyl)-1,3,4-oxadiazole-5-thiol  derivatives.Methods: Antibacterial activities of the compounds were evaluated using broth dilution method in 96 well plates. Enzyme inhibitory activities assays were investigated against α-glucosidase, butyrylcholinesterase (BchE) and lipoxygenase (LOX) using acarbose, eserine and baicalien as reference standards, respectively. A mixture of enzyme, test compound and the substrate was incubated and variation in absorbance noted before and after incubation. In tests for hemolytic activities, the compounds were incubated with red blood cells and variations in absorbance were used as indices their hemolytic activities.Results: The compounds were potent antibacterial agents. Five of them exhibited very good antibacterial potential similar to ciprofloxacin, and had minimum inhibitory concentrations (MIC) of at least 9.00 ± 4.12 μM against S. aureus, E.coli, and B. subtilis. One of the compounds had strong enzyme inhibitory potential against α-glucosidase, with IC50 of 17.11 ± 0.02 μg/mL which was better than that of standard acarbose (IC50 38.25 ± 0.12 μg/mL). Another compound had 1.5 % hemolytic activity. Conclusion: S-Alkylated/aralkylated 2-(1H-indol-3-ylmethyl)-1,3,4-oxadiazole-5-thiol deviratives with valuable antibacterial, anti-enzymatic and hemolytic activities have been successfully synthesized. These compounds may be useful in the development of pharmaceutical products.Keywords: 2-(1H-Indol-3-ylmethyl)-1,3,4-oxadiazole-5-thiol derivatives, Enzyme inhibition, Antibacterial activity, Hemolytic activity, Molecular dockin

Convergent synthesis of new N -substituted 2-{[5-(1H -indol-3-ylmethyl)-1,3,4-oxadiazol-2-yl]sulfanyl}acetamides as suitable therapeutic agents

A series of N-substituted 2-{[5-(1H-indol-3-ylmethyl)-1,3,4-oxadiazol-2-yl]sulfanyl}acetamides (8a-w) was synthesized in three steps. The first step involved the sequential conversion of 2-(1H-indol-3-yl)acetic acid (1) to ester (2) followed by hydrazide (3) formation and finally cyclization in the presence of CS2 and alcoholic KOH yielded 5-(1H-indole-3-yl-methyl)-1,3,4-oxadiazole-2-thiol (4). In the second step, aryl/aralkyl amines (5a-w) were reacted with 2-bromoacetyl bromide (6) in basic medium to yield 2-bromo-N-substituted acetamides (7a-w). In the third step, these electrophiles (7a-w) were reacted with 4 to afford the target compounds (8a-w). Structural elucidation of all the synthesized derivatives was done by 1H-NMR, IR and EI-MS spectral techniques. Moreover, they were screened for antibacterial and hemolytic activity. Enzyme inhibition activity was well supported by molecular docking results, for example, compound 8q exhibited better inhibitory potential against α-glucosidase, while 8g and 8b exhibited comparatively better inhibition against butyrylcholinesterase and lipoxygenase, respectively. Similarly, compounds 8b and 8c showed very good antibacterial activity against Salmonella typhi, which was very close to that of ciprofloxacin, a standard antibiotic used in this study. 8c and 8l also showed very good antibacterial activity against Staphylococcus aureus as well. Almost all compounds showed very slight hemolytic activity, where 8p exhibited the least. Therefore, the molecules synthesized may have utility as suitable therapeutic agents.Uma série de acetamidas 2-{[5-(1H-indol-3-ilmetil)-1,3,4-oxadiazol-2-il]sulfanila} N-substituídas (8a-w) foi sintetizada em três fases. A primeira etapa envolveu a conversão sequencial de ácido 2-(1H-indol-3-il)acético (1) a éster (2), seguido por hidrazida (3) e, finalmente, a e ciclização na presença de CS2 e KOH alcoólico produziu 5-(1H-indol-3-il- metil)-1,3,4-oxadiazole-2-tiol (4). Na segunda etapa, aminas arílicas/aralquílicas(5a-w) reagiram com brometo de 2-bromoacetila (6​​), em meio básico, para se obter acetamidas 2-bromo-N-substituídas (7a-w). Na terceira etapa, estes eletrófilos (7a- w) reagiram com 4, para se obter os compostos alvo (8a-w). A elucidação estrutural de todos os derivados sintetizados foi realizada por 1H-NMR, IR e técnicas de espectrometria de EI-MS. Além disso, eles foram submetidos a triagem de atividade antibacteriana e hemolítica. Análise da inibição enzimática foi bem apoiada pelos resultados de docking molecular. Por exemplo, o composto 8q exibiu melhor potencial inibitório contra α-glicosidase, e os compostos 8g e 8b exibiram, comparativamente, melhor inibição contra butirilcolinesterase (BChE) elipoxigenase (LOX), respectivamente. Do mesmo modo os compostos 8b e 8c mostraram excelente potencial antibacteriano contra SalmonellaTyphi, semelhante ao do ciprofloxacino, antibiótico padrão usado neste estudo. Os compostos 8c e 8l também mostraram excelente potencial antibacteriano contra Staphylococcus aureus . Quase todos os compostos mostraram pequena atividade hemolítica, sendo que o composto 8p apresentou menor atividade. Assim, as moléculas sintetizadas podem ter a sua utilidade como agentes terapêuticos adequados

Recent developments in textile based polymeric smart sensor for human health monitoring: A review

In the modern age, the most important and prevailing issue is the monitoring of human health. To address this, several devices have been developed and a need new materials investigated. The idea of textile-based smart sensors is emerging rapidly. In this regard, ICPs and ECPs have attracted the attention of researchers due to their mechanical adaptability to suit the characteristics of textile fabric. The lighter weight, stretchability and wearability, etc. are considered an advantage while selecting the material for developing sensors not only in health monitoring but also in biomedical, sports, and military fields. The idea behind wearable sensing devices is to enable easy integration of the sensor device into daily life routines. Such wearable sensors also have the potential for real time and online monitoring of human health and integrate with smart monitoring devices. The purpose of this review is to discuss the recent developments in smart monitoring sensors.Open Access funding for this article is provided by the Qatar National Library, Al Luqta Street, Al-Rayyan P.O Box 5825 Doha, Qatar” The authors acknowledge the funding received for this work from Higher Education Commission (HEC) Pakistan under the Technology Development Fund (TDF) for grant number TDF-03-103

Synthesis and in silico study of 2-furyl(4-{4-[(substituted)sulfonyl]benzyl}-1-piperazinyl)methanone derivatives as suitable therapeutic agents

In the study presented here, a new series of 2-furyl(4-{4-[(substituted)sulfonyl]benzyl}-1-piperazinyl)methanone derivatives was targeted. The synthesis was initiated by the treatment of different secondary amines (1a-h) with 4-bromomethylbenzenesulfonyl chloride (2) to obtain various 1-{[4-(bromomethyl)phenyl]sulfonyl}amines (3a-h). 2-Furyl(1-piperazinyl)methanone (2-furoyl-1-piperazine; 4) was then dissolved in acetonitrile, with the addition of K2CO3, and the mixture was refluxed for activation. This activated molecule was further treated with equi-molar amounts of 3a-h to form targeted 2-furyl(4-{4-[(substituted)sulfonyl]benzyl}-1-piperazinyl)methanone derivatives (5a-h) in the same reaction set up. The structure confirmation of all the synthesized compounds was carried out by EI-MS, IR and 1H-NMR spectral analysis. The compounds showed good enzyme inhibitory activity. Compound 5h showed excellent inhibitory effect against acetyl- and butyrylcholinesterase with respective IC50 values of 2.91±0.001 and 4.35±0.004 μM, compared to eserine, a reference standard with IC50 values of 0.04±0.0001 and 0.85±0.001 μM, respectively, against these enzymes. All synthesized molecules were active against almost all Gram-positive and Gram-negative bacterial strains tested. The cytotoxicity of the molecules was also checked to determine their utility as possible therapeutic agents

Pharmacological Evaluation and Synthesis of New Sulfonamides Derivatives Based on 1,4-Benzodioxane

We report here the synthesis of a series of N-aryl-2,3-dihydrobenzo[1,4]dioxine-6-sulfonamide and its N-substituted derivatives with benzyl chloride and ethyl iodide. Initially, 2,3-dihydrobenzo[1,4]dioxine-6-sulfonyl chloride (1) was subjected to react with various aryl amines (2a-e) to afford parent compounds N-aryl-2,3-dihydrobenzo[1,4]dioxine-6-sulfonamide (3a-e). At second step, these parent compounds were reacted with benzyl chloride (4) and ethyl iodide (5) as to synthesize N-benzyl-N-aryl-2,3-dihydrobenzo[1,4]dioxine-6-sulfonamide (6a-e) and N-ethyl-N-aryl-2,3-dihydrobenzo[1,4]dioxine-6-sulfonamide (7a-e) in the presence of lithium hydride and N,Nꞌ-dimethylformamide respectively. FT-IR, Nuclear Magnetic Resonance (1H-NMR) and Mass Spectrometry (MS) techniques were used to investigate the structures of these synthesized compounds. A fingerprinted study was conducted against some enzymes like butyrylcholin-esterase (BChE), acetylcholinesterase (AChE) and lipoxygenase (LOX). This study revealed that most of them demonstrated a moderate activity against butyrylcholinesterase (BChE) and acetylcholinesterase (AChE) however promisingly a good activity against lipoxygenase enzyme was observed. Finally, an antimicrobial and hemolytic activities of these sulfonamides were probed which confirmed that the parent sulfonamides 3b have the proficient antimicrobial activities, while the derivatives 6a, 7a, 7b and 7c explored a good activity against the selected panel of bacterial and fungal species. All the compounds were further computationally docked against (LOX), (BChE) and (AChE) enzymes and these interaction highlighted the importance of sulfonamides in the inhibition of the target enzymes

Whole exome sequence of Pakistani acute lymphocytic leukemia patient from Pakhtuns ancestry reveal the novel genetic variant characterization in the GLDC gene

Background: Acute Lymphoblastic Leukemia (ALL) is the most common malignant disease in children and often involves numerical chromosomal abnormalities, fusion genes, or minor localized deletions that are significant in the development of leukemia. Glycine Decarboxylase (GLDC) gene overexpression and mutation is associated with oncogenic activity in various cancers. However, the pathophysiological roles and structural consequences of GLDC in acute lymphocytic leukemia have not been investigated. Objective: We aimed to identify novel variant in acute lymphocytic leukemia through whole exome sequencing. Methods: This study employs whole exome sequencing to examine seven pediatric patients with Acute Lymphoblastic Leukemia (ALL) in Pakistan. The patients under investigation are of Pakistani origin. The deleterious effect was predicted by SIFT, PolyPhen2, CADD, FATHMM, HOPE, and Mutation Assessors. Structure stability assessment was performed using the I-Mutant-3.0server. The atomic structure of the Single Nucleotide Polymorphism (SNP) was analyzed utilizing the Molecular Dynamics (MD) with WEBGRO server. Results: The present study identified a novel pathogenic heterozygous variant NM_000170.2:p.Ser551Cys/c.1651A>T in GLDC gene of early stage diagnose ALL patient the variant was not present in the dbSNP & 1000Genome Project databases. Structural instability, disrupted function, and altered 3D structure were observed in the mutant GLDC protein model compared to the wild-type structure. Conclusion: The novel SNP was found in a highly conserved region of the GLDC protein and is predicted to be a high-risk candidate for leukemia. This variant greatly affects the stability of the protein