Discrimination of Pakistani Fountain Pen Inks by Gas Chromatography-Mass Spectrometry (GC-MS).

In developing countries, the chances of fraud in written documents are comparatively high. Therefore, comparison of fountain pen inks is especially imperative in examination of forensic questioned documents. We have investigated the use of the gas chromatography-mass spectrometry technique in profiling and discrimination of fountain pen ink used in Pakistan for forensic purpose. The main purpose of this study was to discriminate different Pakistani fountain pen inks. The datum for Pakistani inks of fountain pen is not obtainable. In this research study, blue, black, and green colors fountain pen inks commercially used in Pakistan have been extracted from paper using micropunch and then investigated using the gas chromatography-mass spectrometry technique. Gas chromatography-mass spectrometry (GC-MS) was used to differentiate various brands of different colors of fountain pen inks based on their chemical composition. Molecular ion peaks for different components were obtained, and components were identified on the basis of detected ions. Results have been calculated and compared in terms of discriminating power (D.P.). The D.P. for blue, black, and green inks of fountain pen was 1.0 by using the gas chromatography-mass spectrometry technique.

Microwave-Assisted Synthesis of (Piperidin-1-yl)quinolin-3-yl)methylene)hydrazinecarbothioamides as Potent Inhibitors of Cholinesterases: A Biochemical and In Silico Approach.

Alzheimer's disease (AD), a progressive neurodegenerative disorder, characterized by central cognitive dysfunction, memory loss, and intellectual decline poses a major public health problem affecting millions of people around the globe. Despite several clinically approved drugs and development of anti-Alzheimer's heterocyclic structural leads, the treatment of AD requires safer hybrid therapeutics with characteristic structural and biochemical properties. In this endeavor, we herein report a microwave-assisted synthesis of a library of quinoline thiosemicarbazones endowed with a piperidine moiety, achieved via the condensation of 6/8-methyl-2-(piperidin-1-yl)quinoline-3-carbaldehydes and (un)substituted thiosemicarbazides. The target N-heterocyclic products were isolated in excellent yields. The structures of all the synthesized compounds were fully established using readily available spectroscopic techniques (FTIR, 1H- and 13C-NMR). Anti-Alzheimer potential of the synthesized heterocyclic compounds was evaluated using acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) enzymes. The in vitro biochemical assay results revealed several compounds as potent inhibitors of both enzymes. Among them, five compounds exhibited IC50 values less than 20 µM. N-(3-chlorophenyl)-2-((8-methyl-2-(piperidin-1-yl)quinolin-3-yl)methylene)hydrazine carbothioamide emerged as the most potent dual inhibitor of AChE and BChE with IC50 values of 9.68 and 11.59 µM, respectively. Various informative structure-activity relationship (SAR) analyses were also concluded indicating the critical role of substitution pattern on the inhibitory efficacy of the tested derivatives. In vitro results were further validated through molecular docking analysis where interactive behavior of the potent inhibitors within the active pocket of enzymes was established. Quinoline thiosemicarbazones were also tested for their cytotoxicity using MTT assay against HepG2 cells. Among the 26 novel compounds, there were five cytotoxical and 18 showed proliferative properties.

Modulative effect of a new hydrazide derivative on wheat-induced pulmonary inflammation in rats.

NEW FINDINGS: What is the central question of this study? What is the mechanism of wheat-induced pulmonary inflammation and how does a hydrazide derivative modulate it? What is the main finding and its importance? A hydrazide derivative significantly reduced wheat-induced pulmonary inflammation in a rat model mainly by down-regulating inflammatory cell infiltration, pathological lesions in the lungs and the level of pro-inflammatory cytokines, COX-1, COX-2 and T-cell proliferation. ABSTRACT: We investigated the ameliorative anti-inflammatory effect of a previously synthesized hydrazide derivative (N'-(4-methoxybenzylidene)-6-(4-chlorophenyl)-3-methyl-1-phenyl-1H-pyrazolo[3,4-b]pyridine-4-carbohydrazide; MD) as an immunomodulator in a newly developed allergen-induced pulmonary inflammation (AIPI) rat model. Wheat and thresher dust were used as allergens to induce pulmonary inflammation while MD was used to reverse the inflammatory response. Blood and bronchoalveolar lavage fluid (BALF) were collected after killing the rats and inflammatory cells were counted. Histological analysis of lung airways was carried out by haematoxylin and eosin and periodic acid-Schiff staining while the level of total serum IgE, interleukin (IL)-4, IL-5 and cyclooxygenase (COX)-1 in BALF and in vitro T-cell proliferation in spleen were measured through enzyme-linked immunosorbent assay. mRNA expression level of IL-4, IL-5, IL-13, transforming growth factor ß (TGF-ß), interferon-γ, tumour necrosis factor α, COX-1 and COX-2 was evaluated by qRT-PCR. A liver and kidney function test was used to observe any toxic impact of MD. The results indicated that 2 mg of wheat and thresher dust led to higher levels of inflammatory cytokines in the blood, BALF and lung airways of rats. MD potentially down-regulated the inflammatory cell infiltration in BALF and pathological lesions in the lung airways of AIPI rats. MD significantly suppressed the elevated total serum IgE, along with IL-4, IL-5, IL-13, TGF-ß, COX-1 and COX-2 mRNA expression and T-cell proliferation in spleen. In conclusion, MD at 10 mg kg-1 exhibited a significant reduction in all the markers in both wheat- and thresher dust-induced pulmonary inflammation mainly by inhibiting pro-inflammatory cytokine production and T-cell proliferation. The data suggest that inhibition of the T-cell response may be responsible for the modulative effect of MD in an AIPI rat model.

Breast Cancer in Pakistan a Critical Appraisal of the Situation Regarding Female Health and Where the Nation Stands?

Breast cancer (BC) is the most common malignancy of women worldwide. In the past it was considered as disease of older middle aged women, but the incidence of BC in young females is growing in recent years concordant with studies in Pakistan. In this paper, we reviewed the mutant functions of tumor suppressor genes (BRCA1, BRCA2, p53, ATM and PTEN), epigenetic transformation and involvement of estrogen receptors in development of breast cancer. We further reviewed the current situation of BC in Pakistan that depicts a higher incidence in young females. According to SKMCH and RC data, age group 4549 years is more prone to BC with high rate of incidence 45.42%. A few studies explored the high expression of ER, PR and HER2/neu in Pakistani females. Moreover, presence of BRCA1 (c.1961dupA) mutation in Pakistani shows concordance with data in different areas of world. But we are unable to find an authentic study that can explore epigenetic based transformation of breast tumors in Pakistan. This area of research needs more attention to explore the complete picture of BC in Pakistan.