Decreased acylated and total ghrelin levels in bipolar disorder patients recovering from a manic episode.

BACKGROUND: To date, only few studies have investigated ghrelin levels in bipolar disorders, and all have exclusively measured acylated ghrelin, with none investigating total ghrelin (acylated and des-acylated). We aimed to investigate peripheral levels of acylated and total ghrelin in subjects experiencing a manic episode of bipolar disorder. METHODS: Peripheral levels of acylated and total ghrelin were measured in hospitalised medicated individuals recovering from a manic episode. Enzyme-linked immunosorbent assays (ELISA) were used to measure ghrelin levels in patients and compared with healthy controls. The relationship between ghrelin levels in bipolar disorder, self-reported hunger measures, demographic and clinical parameters was investigated with correlational analyses. RESULTS: Twenty-four subjects (15 males, 9 females) recovering from mania and 27 matched healthy controls (13 males, 14 females) were recruited for the study. Mean values of both acylated (187 vs.520 pg/mL) and total ghrelin (396 vs. 648 pg/mL) were significantly reduced in bipolar disorder (p = 0.001). Ghrelin levels correlated positively with markers of illness severity and negatively with prescribed mood stabilizers, second-generation antipsychotics, weight and body mass index. CONCLUSION: Peripheral measurements of acylated and total ghrelin were both reduced in bipolar disorder patients compared to healthy controls. Whilst illness severity promotes higher ghrelin levels, pharmacological treatment and weight gain exercise the opposite effect.

Overview of approval procedures for bioadhesives in the United States of America and Canada.

Bioadhesives are useful medical devices to help reduce postoperative complications and as adjuncts to sutures and staples in sealing wounds. Biomedical companies have been promoting research and development into new bioadhesives. As for other medical devices, translating promising candidates to market involves the need to pass through several regulatory steps, wherein their safety and effectiveness are evaluated and the proper reimbursements from payors are assessed. The regulatory procedures involve classification based on the risk factors, support studies, submission of applications to relevant authorities, procurement of certification, and finally commercialization, while keeping a track record of the post-market data. The importance of real-world data has been recently realized. The aim of this review is to focus on the translational goals, expectations, and necessities of medical devices focusing on the bioadhesives to be commercialized. It should aid researchers inspired to discover and market new bioadhesives in understanding the need for basic regulatory procedures behind their commercialization for medical usage, most importantly for internal medicine specifically in the United States of America, Canada, and Europe, in part. The key differences in the regulatory aspects among those are highlighted. Regulations keep changing with the introduction of new products and governmental laws. They are updated in this manuscript till March 2021.

Modulation of Stem Cell Progeny by Probiotics during Regeneration of Gastric Mucosal Erosions.

Patients with gastric mucosal erosions are predisposed to chronic gastritis, ulcer or even cancer. The repair of mucosal erosions involves several events including proliferation of gastric epithelial stem cells. The aim of this study was to investigate the effects of the probiotic mixture of De Simone Formulation on gastric epithelial stem cell lineages in mouse models of gastric mucosal erosions. Gastric erosions were induced by a single oral gavage of 80% ethanol containing 15 mg/mL acetylsalicylic acid (5 mL/kg) following a daily dose of probiotic mixture (5 mg/day/mouse) for 10 days. In another protocol, erosions were induced by a daily gavage of acetylsalicylic acid (400 mg/kg/day/mouse) for 5 days before or after daily administration of probiotic mixture for 5 days. Control mice received water gavage for 10 days. All mice were injected with bromodeoxyuridine two hours before sacrifice to label S-phase cells. The stomachs of all mice were processed for histological examination, lectin binding, and immunohistochemical analysis. The results reveal that mice that received probiotics before or after the induction of erosion showed a decrease in erosion index with an increase in gastric epithelial stem/progenitor cell proliferation and enhanced production of mucus, trefoil factors, and ghrelin by mucous and enteroendocrine cell lineages. These mice also showed restoration of the amount of H+,K+-ATPase and pepsinogen involved in the production of the harsh acidic environment by parietal and chief cell lineages. In conclusion, this study demonstrates the beneficial effects of probiotics against gastric mucosal erosion and highlights the involvement and modulation of proliferative stem cells and their multiple glandular epithelial cell lineages.

Effects of Diesel Exhaust Particles on Mouse Gastric Stem Cells.

Stem cells have attracted many scientists because of their unique properties and therapeutic applications. However, very little is known on the environmental toxins that could affect their biological features. This study focuses on the consequences of the exposure of a cell line representative of the mouse gastric stem/progenitor (mGS) cells to diesel exhaust particles (DEPs). These immortal cells were cultured using routine protocols. The DEPs were added to the culture media at 1, 10, and 100 µg/mL for 1 to 72 h. The cells were assayed for their viability, migration, oxidative stress, and the expression of genes specific for cell proliferation, pluripotency, and death. DEPs induced a reduction in the metabolic activity of mGS cells, only at a high concentration of 100 µg/mL. However, no significant effects were detected on cell migration, oxidative stress markers (glutathione and thiobarbituric acid reactive substances), and cell death related proteins/genes. Interestingly, these findings were associated with down-regulation of Notch 2 and 3 and Bmi-1 proteins and activation of STAT3 involved in the regulation of the fate of stem cells. In conclusion, this study demonstrates that mGS cells have some resistance to oxidative stress and apoptosis when exposed to DEPs at the expense of their stemness.

Probiotics Upregulate Trefoil Factors and Downregulate Pepsinogen in the Mouse Stomach.

Probiotics are used in the management of some gastrointestinal diseases. However, little is known about their effects on normal gastric epithelial biology. The aim of this study was to explore how the probiotic mixture VSL#3 affects gastric cell lineages in mice with a special focus on protective and aggressive factors. Weight-matching littermate male mice (n = 14) were divided into treated and control pairs. The treated mice received VSL#3 (5 mg/day/mouse) by gastric gavage for 10 days. Control mice received only the vehicle. Food consumption and bodyweight were monitored. All mice were injected intraperitoneally with bromodeoxyuridine (120 mg/Kg bodyweight) two hours before sacrificed to label S-phase cells. Stomach tissues were processed for lectin- and immunohistochemical examination. ImageJ software was used to quantify immunolabeled gastric epithelial cells. Real-time quantitative polymerase chain reaction was used to provide relative changes in expression of gastric cell lineages specific genes. Results revealed that treated mice acquired (i) increased production of mucus, trefoil factor (TFF) 1 and TFF2, (ii) decreased production of pepsinogen, and (iii) increased ghrelin-secreting cells. No significant changes were observed in bodyweight, food consumption, cell proliferation, or parietal cells. Therefore, VSL#3 administration amplifies specific cell types specialized in the protection of the gastric epithelium.

3D culture of mouse gastric stem cells using porous microcarriers.

The lining epithelium of the stomach includes multipotent stem cells which undergo proliferation and migration-associated differentiation. These cells give rise to multiple cell lineages that produce mucus, acid, pepsinogen and various hormones/peptides. A 3D culture for stem cells would facilitate identification of the factors that control proliferation and/or differentiation programs. Here, we report on the use of disk-like ImmobaSil HD silicone-rubber matrix based microcarriers that are permeable to oxygen and reduce the creation of toxic environment within the center of the microcarrierd for culturing the mouse gastric stem (mGS) cells. We define several parameters that affect the initial cell attachment such as size of cell inoculum, serum concentration, mode and speed of agitation. We show that although such a microcarrier allows for attachment and growth of gastric stem cells, it does not lend itself and does not support the functional differentiation of such cells.