Eupatorin and Salvigenin Potentiate Doxorubicin-Induced Apoptosis and Cell Cycle Arrest in HT-29 and SW948 Human Colon Cancer Cells

Background: Cancer persists as one of the world’s most pressing maladies. Notable points about chemotherapy are drug side effects which are almost universally encountered. Emerging knowledge focusing on mechanisms of toxicity due to chemotherapy has led to characterization of novel methods, including the exploitation of natural compounds, in combination therapies. Flavonoids are natural polyphenolic compounds that play protective roles against tumor cell development. The focus of this study was apoptotic effects of two flavonoids, eupatorin and salvigenin, in combination with doxorubicin on a cellular model of colon cancer. Method: Upon establishing a non-effective dose of doxorubicin, and effective doses of eupatorin (100μM) and salvigenin (150μM) via MTT, morphological features of apoptosis were distinguished using DAPI staining and cell cycle blockage in the sub-G1 phase. Apoptosis was determined by annexin/ PI and western blotting. ROS levels and MMP were measured to show any role of mitochondria in apoptosis. Results: Co-administration of flavonoids with doxorubicin induced apoptosis via the mitochondrial pathway as mitochondrial membrane potential and ROS production were changed. Annexin/PI analysis demonstrated that apoptosis frequency was increased with the combination treatments in colon cancer cells. Finally, the combination of these flavonoids with doxorubicin increased the Bax/Bcl-2 ratio, caspase-3 expression and PARP cleavage. Conclusion: Combination of flavonoids with doxorubicin induces apoptosis and enhances effect on cancer cells which might allow amelioration of side effects by dose lowering.     

Role of ultrasound in confirmation of endotracheal tube in neonates: a review

Tracheal intubation (TI) is a commonly done procedure in neonatal intensive care unit and delivery room during resuscitation. The confirmation of endotracheal tube (ETT) position should be done quickly as tube malposition is associated with various serious adverse outcomes like hypoxemia, right upper lobe collapse, atelectasis, air leak syndromes and esophageal intubation. ETT position can be confirmed by various methods like clinical sign, chest radiography, capnography, external digital tracheal palpation, ultrasonography (USG), respiratory function monitor, video-laryngoscope and fiberoptic devices. The current gold standard test to confirm ETT position is a chest radiograph, but it has many fallacies thus presently there is the need for a modality that helps in detection of endotracheal intubation and tube position with minimal complications. USG has been used in adult and pediatric population for detecting ETT position but there are very less studies in neonates. In this review, we analyze all the published studies, case reports and personal experiences that have sought the use of USG in neonatal population for detection of ETT position.     

Characterization of the CA1 pyramidal neurons in rat model of hepatic cirrhosis: insights into their electrophysiological properties

Although the key contributors of altering neurological function in hepatic encephalopathy are relatively well known, the electrophysiological mechanism of CA1 damage, a key vulnerable area during hyperammonemia, have not yet been defined. Therefore, here we focus on the electrophysiological mechanisms of cognitive impairments following bile duct ligation (BDL). We performed patch-clamp recordings from the CA1 pyramidal neurons in hippocampus of male Wistar rats, which underwent sham or BDL surgery. A striking electrophysiological change of hippocampal neurons in experimental model of BDL was observed in the present study. Spontaneous firing frequency and rate of action potential (AP) rebound was decreased and afterhyperpolarization amplitude (AHP) was increased significantly in hippocampal cells of BDL animals compared to sham group. Together, the results suggest that altered intrinsic properties of the hippocampal neurons may contribute to the cognitive abnormalities during hepatic encephalopathy (HE), highlighting the electrophysiological mechanisms for providing new treatments against HE.

     

Nanomaterial interactions with and trafficking across the lung alveolar epithelial barrier: implications for health effects of air-pollution particles

Studies on the health effects of air-pollution particles suggest that injury may result from inhalation of airborne ultrafine particles (<100 nm in diameter). Engineered nanomaterials (<100 nm in at least one dimension) may also be harmful if inhaled. Nanomaterials deposited on the respiratory epithelial tract are thought to cross the air-blood barrier, especially via the expansive alveolar region, into the systemic circulation to reach end organs (e.g., myocardium, liver, pancreas, kidney, and spleen). Since ambient ultrafine particles are difficult to track, studies of defined engineered nanomaterials have been used to obtain valuable information on how nanomaterials interact with and traffic across the air-blood barrier of mammalian lungs. Since specific mechanistic information on how nanomaterials interact with the lung is difficult to obtain using in vivo or ex vivo lungs due to their complex anatomy, in vitro alveolar epithelial models have been of considerable value in determining nanomaterial-lung interactions. In this review, we provide information on mechanisms underlying lung alveolar epithelial injury caused by various nanomaterials and on nanomaterial trafficking across alveolar epithelium that may lead to end-organ injury.     

Nephrogenic systemic fibrosis: a case report and review of the literature

The authors report a case of a patient who presented with thick, indurated, hyperpigmented plaques of the bilateral upper and lower extremities, ultimately discovered to be attributed to nephrogenic systemic fibrosis. The case was written to highlight the clinical manifestations of nephrogenic systemic fibrosis, as well as to make dermatologists aware of this disease, their role in diagnosis and management, and review treatment options.     

Polystyrene nanoparticle trafficking across MDCK-II

Polystyrene nanoparticles (PNP) cross rat alveolar epithelial cell monolayers via non-endocytic transcellular pathways. To evaluate epithelial cell type-specificity of PNP trafficking, we studied PNP flux across Madin Darby canine kidney cell II monolayers (MDCK-II). The effects of calcium chelation (EGTA), energy depletion (sodium azide (NaN₃) or decreased temperature), and endocytosis inhibitors methyl-β-cyclodextrin (MBC), monodansylcadaverine and dynasore were determined. Amidine-modified PNP cross MDCK-II 500 times faster than carboxylate-modified PNP. PNP flux did not increase in the presence of EGTA. PNP flux at 4°C and after treatment with NaN₃ decreased 75% and 80%, respectively. MBC exposure did not decrease PNP flux, whereas dansylcadaverine- or dynasore-treated MDCK-II exhibited ∼80% decreases in PNP flux. Confocal laser scanning microscopy revealed intracellular colocalization of PNP with clathrin heavy chain. These data indicate that PNP translocation across MDCK-II (1) occurs via clathrin-mediated endocytosis and (2) is dependent on PNP physicochemical properties. We conclude that uptake/trafficking of nanoparticles (NPs) into/across epithelia depends both on properties of the NPs and on the specific epithelial cell type.

From the Clinical Editor

This basic science study investigates the membrane translocation of polystyrene nanoparticles (PNP) via an epithelial cell monolayer utilizing canine kidney cells. The authors conclude that translocation occurs via clathrin-mediated endocytosis and is dependent on the physicochemical properties of the particular PNP.     

Sheep practice eye for ophthalmic surgery training in skills laboratory

Pig eyes are not available for surgical practice in the Middle East and Central Asia. We reviewed the literature to select an alternative animal practice eye based on biometry, availability, expense, and the ethical issue of animal sacrifice. Twenty enucleated sheep eyes were studied with an ultrasonography immersion technique, and a variety of techniques for globe harvesting were tested and compared. The sheep eye was judged to be the best practical choice for ophthalmic surgery practice and the "bone shattering" exenteration maneuver, the most efficient harvesting method. Several anterior segment procedures were performed in the sheep eyes. Introduction of this sheep model would be instrumental in the development of ophthalmology skills laboratories and surgical training in Middle Eastern and Central Asian regions. FINANCIAL DISCLOSURE: No author has a financial or proprietary interest in any material or method mentioned.     

Anetoderma treated with combined 595-nm pulsed-dye laser and 1550-nm non-ablative fractionated laser

Anetoderma is a skin disorder characterized by a focal loss of dermal elastic tissue whereby patients present with soft, depressible lesions. We postulated that a series of combination treatment using the 595-nm pulsed dye laser (PDL) and the 1550-nm non-ablative fractionated laser (NAFL) would improve the anetoderma lesions. Our patient with biopsy proven anetoderma received 3 treatments with a combination of 595-nm PDL and 1550-nm NAFL spaced 3 weeks apart. Skin biopsies were performed at baseline and immediately prior to the third treatment. Stains for hematoxylin and eosin and Verhoeff Van Gieson (VVG) were performed. Improvement in lesion color, texture, and overall appearance was noted after the second treatment and continued following the third treatment. Post-treatment VVG staining demonstrated an increase in dermal elastin fibers and a decrease in elastin fiber fragmentation. Thus, the combination of 595-nm PDL and 1550-nm NAFL should be considered as a treatment modality for anetoderma.