In vitro Response of Intestinal Segments of Mice with Hereditary Muscular Dystrophy to Various Pharmacologic Agents.

Patients with Duchenne muscular dystrophy (DMD) are susceptible to numerous adverse intraoperative and postoperative side effects of anesthetic agents. These include: hyperthermia and hyperkalemia,1,2 systemic acidosis,3 cardiac abnormalities (tachycardia, arrhythmia, arrest),2-5 rhabdomyolysis,2-6 as well as death.2,5 These clinical and laboratory findings are similar to those associated with malignant hyperthermia (MH).7,8 Until this time no one has confirmed the association of MH, as reflected by these clinical phenomena, in a patient with DMD. We present a patient who manifested many features of MH immediately following confirmatory muscle biopsy for DMD under general anesthesia. In vitro response to testing of a muscle biopsy specimen was consistent with a diagnosis of malignant hyperthermia.

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Electron Microscopy of Fibroblasts from Myotonic Muscular Dystrophy Patients

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100098976 ◽

1981 ◽

Vol 39 ◽

pp. 498-499

Author(s):

S. E. Miller ◽

G. B. Hartwig ◽

R. A. Nielsen ◽

A. P. Frost ◽

A. D. Roses

Keyword(s):

Electron Microscopy ◽

Muscular Dystrophy ◽

Genetic Diseases ◽

Skin Fibroblasts ◽

Inborn Errors ◽

Cytoplasmic Inclusions ◽

Cultured Skin ◽

Myotonic Muscular Dystrophy ◽

Glycosaminoglycan Metabolism

Many genetic diseases can be demonstrated in skin cells cultured in vitro from patients with inborn errors of metabolism. Since myotonic muscular dystrophy (MMD) affects many organs other than muscle, it seems likely that this defect also might be expressed in fibroblasts. Detection of an alteration in cultured skin fibroblasts from patients would provide a valuable tool in the study of the disease as it would present a readily accessible and controllable system for examination. Furthermore, fibroblast expression would allow diagnosis of fetal and presumptomatic cases. An unusual staining pattern of MMD cultured skin fibroblasts as seen by light microscopy, namely, an increase in alcianophilia and metachromasia, has been reported; both these techniques suggest an altered glycosaminoglycan metabolism An altered growth pattern has also been described. One reference on cultured skin fibroblasts from a different dystrophy (Duchenne Muscular Dystrophy) reports increased cytoplasmic inclusions seen by electron microscopy. Also, ultrastructural alterations have been reported in muscle and thalamus biopsies from MMD patients, but no electron microscopical data is available on MMD cultured skin fibroblasts.

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Transcriptome comparisons of in vitro intestinal epithelia grown under static and microfluidic gut-on-chip conditions with in vivo human epithelia

Scientific Reports ◽

10.1038/s41598-021-82853-6 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Kornphimol Kulthong ◽

Guido J. E. J. Hooiveld ◽

Loes Duivenvoorde ◽

Ignacio Miro Estruch ◽

Victor Marin ◽

...

Keyword(s):

Gene Expression ◽

Culture Conditions ◽

Gene Set Enrichment Analysis ◽

Shear Stresses ◽

Static Culture ◽

Dynamic Culture ◽

Intestinal Segments ◽

On Chip

AbstractGut-on-chip devices enable exposure of cells to a continuous flow of culture medium, inducing shear stresses and could thus better recapitulate the in vivo human intestinal environment in an in vitro epithelial model compared to static culture methods. We aimed to study if dynamic culture conditions affect the gene expression of Caco-2 cells cultured statically or dynamically in a gut-on-chip device and how these gene expression patterns compared to that of intestinal segments in vivo. For this we applied whole genome transcriptomics. Dynamic culture conditions led to a total of 5927 differentially expressed genes (3280 upregulated and 2647 downregulated genes) compared to static culture conditions. Gene set enrichment analysis revealed upregulated pathways associated with the immune system, signal transduction and cell growth and death, and downregulated pathways associated with drug metabolism, compound digestion and absorption under dynamic culture conditions. Comparison of the in vitro gene expression data with transcriptome profiles of human in vivo duodenum, jejunum, ileum and colon tissue samples showed similarities in gene expression profiles with intestinal segments. It is concluded that both the static and the dynamic gut-on-chip model are suitable to study human intestinal epithelial responses as an alternative for animal models.

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Microstructure and surface texture driven improvement in in-vitro response of laser surface processed AZ31B magnesium alloy

Journal of Magnesium and Alloys ◽

10.1016/j.jma.2020.11.002 ◽

2021 ◽

Author(s):

Tso-Chang Wu ◽

Sameehan S. Joshi ◽

Yee-Hsien Ho ◽

Mangesh V. Pantawane ◽

Subhasis Sinha ◽

...

Keyword(s):

Magnesium Alloy ◽

Surface Texture ◽

Laser Surface ◽

Az31b Magnesium Alloy ◽

In Vitro Response

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Loss of Nitric Oxide Induces Fibrogenic Response in Organotypic 3D Co-Culture of Mammary Epithelia and Fibroblasts—An Indicator for Breast Carcinogenesis

Cancers ◽

10.3390/cancers13112815 ◽

2021 ◽

Vol 13 (11) ◽

pp. 2815

Author(s):

Gang Ren ◽

Xunzhen Zheng ◽

Vandana Sharma ◽

Joshua Letson ◽

Andrea L. Nestor-Kalinoski ◽

...

Keyword(s):

Nitric Oxide ◽

Culture System ◽

Epithelial Mesenchymal Transition ◽

Precancerous Lesions ◽

Three Dimensional ◽

Epidemiological Studies ◽

Mesenchymal Transition ◽

In Vitro Response ◽

Mammary Epithelia

Excessive myofibroblast activation, which leads to dysregulated collagen deposition and the stiffening of the extracellular matrix (ECM), plays pivotal roles in cancer initiation and progression. Cumulative evidence attests to the cancer-causing effects of a number of fibrogenic factors found in the environment, diseases and drugs. While identifying such factors largely depends on epidemiological studies, it would be of great importance to develop a robust in vitro method to demonstrate the causal relationship between fibrosis and cancer. Here, we tested whether our recently developed organotypic three-dimensional (3D) co-culture would be suitable for that purpose. This co-culture system utilizes the discontinuous ECM to separately culture mammary epithelia and fibroblasts in the discrete matrices to model the complexity of the mammary gland. We observed that pharmaceutical deprivation of nitric oxide (NO) in 3D co-cultures induced myofibroblast differentiation of the stroma as well as the occurrence of epithelial–mesenchymal transition (EMT) of the parenchyma. Such in vitro response to NO deprivation was unique to co-cultures and closely mimicked the phenotype of NO-depleted mammary glands exhibiting stromal desmoplasia and precancerous lesions undergoing EMT. These results suggest that this novel 3D co-culture system could be utilized in the deep mechanistic studies of the linkage between fibrosis and cancer.

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