Isolation and Characterisation of Degradation Impurities in the Cefazolin Sodium Drug Substance

Two unknown impurities were detected in the cefazolin sodium bulk drug substance using gradient reversed-phase high-performance liquid chromategraphy (HPLC). These impurities were isolated by preparative HPLC and characterized by using spectroscopic techniques like LC-MS, LC-MS/MS, 1D, 2D NMR, and FT-IR. Based on the spectral data, the impurities have been characterized as N-(2,2-dihydroxyethyl)-2-(1H-tetrazol-1-yl)acetamide (Impurity-I) and 2-{carboxy[(1H-tetrazol-1-ylacetyl)amino]methyl}-5-methylidene-5,6-dihydro-2H-1,3-thiazine-4-carboxylic acid (Impurity-II). The structures of these impurities were also established unambiguously by co-injection into HPLC to confirm the retention time. To the best of our knowledge, these two impurities were not reported elsewhere.     

Anticlastogenic effect of diosgenin on 7,12-dimethylbenz(a)anthracene treated experimental animals

The maintenance of stable test atmospheres in small-volume inhalation systems such as a nose-only exposure manifold requires rapid and appropriate responses to fluctuations in a number of parameters. For example, changes in flows or voltages can affect test compound generation efficiency and gas dilution ratios, resulting in excursions of the test concentration outside an acceptable range. A feedback control loop was designed that makes use of mass flow controllers in maintaining the target concentration of a test compound. The system was tested by generating ozone in a nose-only exposure manifold. An ozone analyzer provided updated concentration values every 30 s, which were compared to the user-defined target concentration recorded in the interface readout box. Values of gain, integral, and lead determining an appropriate response of the controller to concentration fluctuations were implemented based on proportional-integral-derivative control algorithms. Using this approach, the flow of ozone mixed with dilution air into the system was adjusted as required without user intervention, minimizing concentration overshoots upon system startup, maintaining an ozone concentration within a range 5% of the target concentration, and responding rapidly and efficiently to line disturbances.     

Biophysics of cell membrane lipids in cancer drug resistance: Implications for drug transport and drug delivery with nanoparticles

In this review, we focus on the biophysics of cell membrane lipids, particularly when cancers develop acquired drug resistance, and how biophysical changes in resistant cell membrane influence drug transport and nanoparticle-mediated drug delivery. Recent advances in membrane lipid research show the varied roles of lipids in regulating membrane P-glycoprotein function, membrane trafficking, apoptotic pathways, drug transport, and endocytic functions, particularly endocytosis, the primary mechanism of cellular uptake of nanoparticle-based drug delivery systems. Since acquired drug resistance alters lipid biosynthesis, understanding the role of lipids in cell membrane biophysics and its effect on drug transport is critical for developing effective therapeutic and drug delivery approaches to overcome drug resistance. Here we discuss novel strategies for (a) modulating the biophysical properties of membrane lipids of resistant cells to facilitate drug transport and regain endocytic function and (b) developing effective nanoparticles based on their biophysical interactions with membrane lipids to enhance drug delivery and overcome drug resistance.     

Amoeboid microglia in the periventricular white matter induce oligodendrocyte damage through expression of proinflammatory cytokines via MAP kinase signaling pathway in hypoxic neonatal rats

Hypoxic injury in the perinatal period results in periventricular white matter (PWM) lesions with axonal damage and oligodendroglial loss. It also alters macrophage function by perpetuating expression of inflammatory mediators. Relevant to this is the preponderance of amoeboid microglial cells (AMC) characterized as active macrophages in the developing PWM. This study aimed to determine if AMC produce proinflammatory cytokines that may be linked to the oligodendroglial loss observed in hypoxic PWM damage (PWMD). Wistar rats (1 day old) were subjected to hypoxia, following which upregulated expression of tumor necrosis factor-alpha (TNF-alpha), interleukin-1beta (IL-1beta), TNF receptor 1 (TNF-R(1)) and IL-1 receptor 1 (IL-1R(1)) was observed. This was coupled with apoptosis and expression of TNF-R(1) and IL-1R(1) in oligodendrocytes. Primary cultured microglial cells subjected to hypoxia (3% oxygen, 5% CO(2) and 92% nitrogen) showed enhanced expression of TNF-alpha and IL-1beta. Furthermore, mitogen-activated protein (MAP) kinase signaling pathway was involved in the expression of TNF-alpha and IL-1beta in microglia subjected to hypoxia. Our results suggest that following a hypoxic insult, microglial cells in the neonatal rats produce inflammatory cytokines such as TNF-alpha and IL-1beta via MAP kinase signaling pathway. These cytokines are detrimental to oligodendrocytes resulting in PWM lesion.     

Chemical composition and larvicidal activity of essential oil from <Emphasis Type="Italic">Mentha spicata</Emphasis> (Linn.) against three mosquito species

Mosquitoes are blood-feeding insects and serve as the most important vectors for spreading human diseases such as malaria, yellow fever, dengue fever, and filariasis. The continued use of synthetic insecticides has resulted in resistance in mosquitoes. Synthetic insecticides are toxic and affect the environment by contaminating soil, water, and air, and then natural products may be an alternative to synthetic insecticides because they are effective, biodegradable, eco-friendly, and safe to environment. Botanical origin may serve as suitable alternative biocontrol techniques in the future. Mentha spicata, an edible and medicinal plant, is chiefly distributed in Southeast Asia and South Asia. In the present study, the toxicity of mosquito larvicidal activity of leaf essential oil (EO) and their major chemical constituents from Mentha spicata against Culex quinquefasciatus, Aedes aegypti, and Anopheles stephensi. The chemical composition of the leaf EO was analyzed using gas chromatography–mass spectroscopy (GC-MS). GC-MS revealed that the EO of M. spicata contained 18 compounds. The major chemical components identified were carvone (48.60%), cis-carveol (21.30%), and limonene (11.30%). The EO had a significant toxic effect against early third-stage larvae of C. quinquefasciatus, A. aegypti, and A. stephensi with LC₅₀ values of 62.62, 56.08, and 49.71 ppm and LC₉₀ values of 118.70, 110.28, and 100.99 ppm, respectively. The three major pure constituents extracted from the M. spicata leaf EO were also tested individually against three mosquito larvae. The LC₅₀ values of carvone, cis-carveol, and limonene appeared to be most effective against A. stephensi (LC₅₀ 19.33, 28.50, and 8.83 ppm) followed by A. aegypti (LC₅₀ 23.69, 32.88, and 12.01 ppm), and C. quinquefasciatus (LC₅₀ 25.47, 35.20, and 14.07 ppm). The results could be useful in search for newer, safer, and more effective natural larvicidal agents against C. quinquefasciatus, A. aegypti, and A. stephensi.     

An unusual ECG pattern in restrictive cardimyopathy

Restrictive cardiomyopathy is the least common type of primary cardiomyopathies. Electrocardiographic recording is abnormal in 99% of patients with RCM. Biatrial enlargement, obliquely elevated ST segment with notched or biphasic late peaking T waves are considered characteristic ECG finding. Significant ST depression with T inversion mimicking subendocardial ischemia has also been reported in patients with RCM and is even suggested as a predictor of sudden cardiac death. We noted a similar ECG pattern in a 16 yr girl with Idiopathic restrictive cardiomyopathy. Coronaries were normal, stress perfusion imaging did not show any perfusion defect. This diffuse resting ST depression with T inversion in precordial & inferior leads along with ST elevation in aVR was persistent for more than six months.