Electrospun microporous gelatin–polycaprolactone blend tubular scaffold as a potential vascular biomaterial

The work reported involved the fabrication of an electrospun tubular conduit of a gelatin and polycaprolactone (PCL) blend as an adventitia‐equivalent construct. Gelatin was included as the matrix for increased biocompatibility with the addition of PCL for durability. This is contrary to most of the literature available for biomaterials based on blends of gelatin and PCL where PCL is the major matrix. The work includes the assiduous selection of key electrospinning parameters to obtain smooth bead‐free fibres with a narrow distribution of pore size and fibre diameter. Few reports elucidate the optimization of all electrospinning parameters to fabricate tubular conduits with a focus on obtaining homogeneous pores and fibres. This stepwise investigation would be unique for the fabrication of gelatin–PCL electrospun tubular constructs. The fabricated microfibrous gelatin–PCL constructs had pores of size ca 50–100 μm reportedly conducive for cell infiltration. The measured value of surface roughness of 57.99 ± 17.4 nm is reported to be favourable for protein adhesion and cell adhesion. The elastic modulus was observed to be similar to that of the tunica adventitia of the native artery. Preliminary in vitro and in vivo biocompatibility tests suggest safe applicability as a biomaterial. Minimal cytotoxicity was observed using MTT assay. Subcutaneous implantation of the scaffold demonstrated acute inflammation which decreased by day 15. The findings of this study could enable the fabrication of smooth bead‐free microfibrous gelatin–PCL tubular construct as viable biomaterial which can be included in a bilayer or a trilayer scaffold for vascular tissue engineering. © 2019 Society of Chemical Industry     

Development of LTCC micro-hotplate with PTC temperature sensor for gas-sensing applications

Low temperature co-fired ceramic (LTCC) micro-hotplates show wide applications in gas sensors and micro-fluidic devices. It is easily structured in three-dimensional structures. This paper presents the low power consumption micro-hotplates which were developed with PTC (positive temperature coefficient) temperature sensor and inter-digitated electrodes. The paper presents two different structures for micro-hotplate with platinum as a heating element. The PTC temperature sensor using two different materials viz. PdAg and platinum paste are developed with micro-hotplates. The simulation has been achieved through COMSOL for LTCC and alumina micro-hotplates. The temperature variation with power consumption has been measured for the developed LTCC micro-hotplates. The change in resistance of PTC temperature sensors was measured with micro-hotplate temperature. The aim of this study was to place a temperature sensor with the gas sensor module to measure and control the temperature of micro-hotplate. A SnO₂ sensing layer is coated on LTCC micro-hotplate using screen printing and characterized for the sensing of carbon monoxide gas (CO). This study will be beneficial for designing hotplates based on LTCC technology with low power consumption and better stability of temperature for gas-sensing applications.     

Cytotoxic effects of topotecan combined with various anticancer agents in human cancer cell lines

BACKGROUND: Topotecan (TPT) is a topoisomerase I poison that exhibits antineoplastic activity. Analysis of the cytotoxic effects of combinations of TPT and other anticancer agents has been limited. PURPOSE: We assessed the cytotoxic effects produced by combinations of TPT and other antineoplastic agents in experiments involving multiple human cancer cell lines of diverse histologic origins. METHODS: The cytotoxic effects of various antimetabolites (fluorouracil, methotrexate, or cytarabine), antimicrotubule agents (vincristine or paclitaxel [Taxol]), DNA alkylating agents (melphalan, bis[chloroethyl]nitrosourea [BCNU], or 4-hydroperoxycyclophosphamide [4HC]), and a DNA-platinating agent (cisplatin), alone and in combination with TPT, were measured in clonogenic (i.e., colony-forming) assays. HCT8 ileocecal adenocarcinoma, A549 non-small-cell lung carcinoma, NCI-H82ras(H) lung cancer, T98G glioblastoma, and MCF-7 breast cancer cell lines were used in these assays. The data were analyzed by the median effect method, primarily under the assumption that drug mechanisms of action were mutually nonexclusive (i.e., completely independent of one another). For each level of cytotoxicity (ranging from 5% to 95%), a drug combination index (CI) was calculated. A CI less than 1 indicated synergy (i.e., the effect of the combination was greater than that expected from the additive effects of the component agents), a CI equal to 1 indicated additivity, and a CI greater than 1 indicated antagonism (the effect of the combination was less than that expected from the additive effects of the component agents). RESULTS: When the mechanisms of drug action were assumed to be mutually nonexclusive, virtually all CIs for combinations of TPT and either antimetabolites or antimicrotubule agents revealed cytotoxic effects that were less than additive. The CIs calculated at low-to-intermediate levels of cytotoxicity for combinations of TPT and the DNA alkylating agents melphalan, BCNU, and 4HC also showed drug effects that were less than additive; in most cases, however, nearly additive or even synergistic effects were observed with these same drug combinations at high levels of cytotoxicity (i.e., at > or = 90% inhibition of colony formation). Results obtained with combinations of TPT and cisplatin varied according to the cell line examined. With A549 cells, less than additive effects were seen at low-to-intermediate levels of cytotoxicity, and more than additive effects were seen at high levels of cytotoxicity. With NCI-H82ras(H) cells, synergy was observed over most of the cytotoxicity range. CONCLUSIONS AND IMPLICATIONS: TPT cytotoxicity appears to be enhanced more by combination with certain DNA-damaging agents than by combination with antimetabolites or antimicrotubule agents. Interactions between TPT and other drugs can vary depending on the cell type examined. Further investigation is required to determine the basis of the observed effects and to determine whether these in vitro findings are predictive of results obtained in vivo.     

Apoptosis and delayed neuronal damage after carbon monoxide poisoning in the rat

Delayed neurological damage after CO hypoxia was studied in rats to determine whether programmed cell death (PCD), in addition to necrosis, is involved in neuronal death. In rats exposed to either air or CO (2500 ppm), microdialysis in brain cortex and hippocampus was performed to determine the extent of glutamate release and hydroxyl radical generation during the exposures. Groups of control and CO-exposed rats also were tested in a radial maze to assess the effects of the CO exposures on learning and memory. At 3, 7, and 21 days after CO exposure brains were perfusion-fixed and hematoxylin-eosin (H&E) was used to assess injury and to select regions for further examination. DNA fragmentation was sought by examining cryosections with the terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick-end labeling (TUNEL) reaction. We found significant increases in glutamate release and .OH generation during and immediately after CO hypoxia. CO-exposed rats showed learning and memory deficits after exposure associated with heterogeneous cell loss in cortex, globus pallidus, and cerebellum. The frontal cortex was affected most seriously; the damage was slight at Day 3, increased at Day 7, and persistent at Day 21 after CO exposure. TUNEL staining was positive at all three time points, and TUNEL-labeled cells were distributed similarly to eosinophilic cells. The number of cells stained by TUNEL was less than by H&E and amounted to 2 to 5% of all cell nuclei in regions of injury. Ultrastructural features of both neuronal necrosis and apoptosis also were observed readily by electron microscopy. These findings indicate that both necrosis and apoptosis (PCD) contribute to CO poisoning-induced brain cell death.     

Surveillance of developmental disabilities with an emphasis on special studies

The developing central nervous system seems to be particularly vulnerable to chemical insults. A model for developmental disabilities surveillance is presented that provides a reasonable framework for monitoring the prevalence of various developmental abnormalities in human populations. Effective monitoring will not only increase the likelihood of detecting the adverse effects of new physical or chemical agents in the environment but will provide a readily available case series for specially directed case-control studies. A specific example is provided of a large case-control study of cerebral palsy and intrapartum magnesium exposure among very low birth weight children, which is being conducted within the framework of a developmental disabilities surveillance program.     

Effect of transluminal angioplasty on cerebral blood flow in the management of symptomatic vasospasm following aneurysmal subarachnoid hemorrhage

In this study the authors have examined the effects of transluminal angioplasty on cerebral blood flow (CBF) in the management of intractable vasospasm following aneurysmal subarachnoid hemorrhage (SAH). Fourteen consecutively enrolled patients underwent attempted angioplasty with or without intraarterial infusion of papaverine. Twelve patients underwent pre- and postangioplasty xenon-enhanced computerized tomography (Xe-CT) scanning to measure regional CBF in 55 to 65 regions of interest (ROIs) per patient. Angioplasty was possible in 13 (93%) of 14 patients, with angiographically demonstrated improvement in all 13. Twelve (92%) of the 13 patients were neurologically improved following angioplasty; seven (58%) of the 12 patients who improved had a complete reversal of all delayed ischemic deficits. Angioplasty significantly decreased the mean number of ROIs at risk (11.4 ROIs pre- and 0.9 ROIs postangioplasty) (p < 0.00005, t-test). All patients had a reduction in the number of ROIs at risk after angioplasty; six (50%) of 12 no longer had any ROIs remaining at risk after angioplasty. Angioplasty significantly increased the mean CBF within at-risk ROIs (13 ml/100 g/minute pre- and 44 ml/100 g/minute postangioplasty) (p < 0.00005, t-test). All patients experienced an improvement in mean CBF in at-risk ROIs after angioplasty, with the mean CBF improving to above 20 ml/100 g/minute in all cases. No differences in the degree of improvement were found in patients who received intraarterial papaverine compared with those who did not. In the majority of patients with refractory vasospasm following SAH, angioplasty effectively dilated spastic arteries, reversed delayed neurological deficits, and significantly improved CBF in areas of brain at risk of infarction.     

Using Web resources to construct multilingual medical thesaurus for cross-language medical information retrieval

Due to the language barrier, non-English users are unable to retrieve the most updated medical information from the U.S. authoritative medical websites, such as PubMed and MedlinePlus. However, currently, there is no any cross-language medical information retrieval (CLMIR) system that can help Chinese-speaking consumers cross the language barrier in finding useful English medical information. A few CLMIR systems utilize MeSH (Medical Subject Headings) to help overcome the language barrier. Unfortunately, the traditional Chinese version of MeSH is currently unavailable.In this paper, we employ a semi-automatic term translation method to construct a Chinese–English MeSH by exploiting abundant multilingual Web resources, including Web anchor texts and search–result pages. Through this method, we have developed a Chinese–English Mesh Compilation System to assist knowledge engineers in compiling a Chinese–English medical thesaurus with more than 19,000 entries. Furthermore, this thesaurus has been used to develop a prototypical system for cross-language medical information retrieval, MMODE, which can help consumers retrieve top-quality English medical information using Chinese terms.