Applying chemical bile duct embolization to achieve chemical hepatectomy in hepatolithiasis: a further experimental study

Background

Hepatolithiasis is the presence of calculi within the bile ducts of the liver. It represents a significant problem for hepatobiliary surgery because of its high recurrence rate and the associated risk for partial hepatectomy. This study was designed to explore the long-term efficacy of chemical biliary duct embolization (CBDE) to treat recurrent hepatolithiasis.

Materials and methods

A rabbit model of hepatolithiasis was established, and CBDE was achieved using oxybenzene and N-butyl-cyanoacrylate. The short-term (6 wk) and long-term (12 wk) efficacy of CBDE treatment was compared by observing the degree of atrophy, fibrosis, proliferation of collagen fibers, and apoptosis of hepatocytes and hepatic stellate cells in the embolized hepatic lobe. Biochemical measurement of β-glucuronidase was also evaluated to determine the effect of CBDE on stone formation.

Results

Six weeks after CBDE, there was liver cell destruction, collagen accumulation, and bile duct proliferation only in the peripheral part of the target lobe. Twelve weeks after CBDE, “self-cut” chemical hepatectomy was achieved, as manifested by the destruction of almost all the hepatocytes in the target lobe, bile duct proliferation, and collagen fiber accumulation. The β-glucuronidase activity was markedly lower in the embolized lobe than in the nonembolized lobe. In contrast, bax, caspase-3, caspase-9, and α-smooth muscle actin expression was substantially higher in the embolized lobe than in the sham-operation group at 6 wk, but was lower at 12 wk.

Conclusions

CBDE is a potentially effective therapeutic approach for treating and preventing the recurrence of hepatolithiasis.     

New players in high fat diet-induced obesity: LETM1 and CTMP

Objective

Obesity contributes to insulin resistance and is a risk factor for diabetes. C-terminal modulator protein (CTMP) and leucine zipper/EF-hand-containing transmembrane protein 1 (LETM1) have been reported to influence the phosphoinositide 3-kinase (PI3K)/protein kinase B (PKB) signaling pathway via the modulation of PKB activity, a key player for insulin signaling. However, it remains unclear whether CTMP and LETM1 are associated with PI3K/PKB signaling in mouse models of obesity.

Materials/Methods

To address this question, we used two different mouse models of obesity, including high-fat diet (HFD)-induced diabetic mice and genetically modified obese mice (ob/ob mice). The levels of insulin-signaling molecules in these mice were determined by immunohistochemical and Western blot analyses. The involvement of CTMP and LETM1 in PI3K/PKB signaling was investigated in HEK293 cells by transient transfection and adenovirus-mediated infection.

Results

We found that the levels of insulin receptor, phosphorylated PKB, and LETM1 were lower and the level of CTMP was higher in the adipose tissue of obese mice on an HFD compared to lean mice on a chow diet. Similar results were obtained in ob/ob mice. In HEK293 cells, the activation of PKB increased the LETM1 level, and inhibition of PKB increased the CTMP level. The overexpression of CTMP suppressed the insulin-induced increase in PKB phosphorylation, which was abrogated by co-overexpression with LETM1.

Conclusion

These results suggest that CTMP and LETM1 may participate in impaired insulin signaling in the adipose tissue of obese mice, raising the possibility that these parameters may serve as new candidate biomarkers or targets in the development of new therapeutic approaches for diabetes.     

Endoscopic mask innovation and protective measures changes during the coronavirus disease-2019 pandemic: Experience from a Chinese hepato-biliary-pancreatic unit

Endoscopy is widely used as a clinical diagnosis and treatment method for certain hepatobiliary and pancreatic diseases. However, due to the distinctive epidemiological characteristics of severe acute respiratory syndrome coronavirus 2, the virus causing coronavirus disease-2019 (COVID-19), healthcare providers are exposed to the patient's respiratory and gastrointestinal fluids, rendering endoscopy a high risk for transmitting a nosocomial infection. This article introduces preventive measures for endoscopic treatment enacted in our medical center during COVID-19, including the adjustment of indications, the application of endoscope protective equipment, the design and application of endoscopic masks and splash-proof films, and novel recommendations for bedside endoscope pre-sterilization.     

Estimating the Cost to U.S. Health Departments to Conduct HIV Surveillance

Objectives

HIV case surveillance is a primary source of information for monitoring HIV burden in the United States and guiding the allocation of prevention and treatment funds. While the number of people living with HIV and the need for surveillance data have increased, little is known about the cost of surveillance. We estimated the economic cost to health departments of conducting high-quality HIV case surveillance.

Methods

We collected primary data on the unit cost and quantity of resources used to operate the HIV case surveillance program in Michigan, where HIV burden (i.e., the number of HIV cases) is moderate to high (n=14,864 cases). Based on Michigan''s data, we projected the expected annual HIV surveillance cost for U.S., state, local, and territorial health departments. We based our cost projection on the variation in the number of new and established cases, area-specific wages, and potential economies of scale.

Results

We estimated the annual total HIV surveillance cost to the Michigan health department to be $1,286,524 ($87/case), the annual total cost of new cases to be $108,657 ($133/case), and the annual total cost of established cases to be $1,177,867 ($84/case). Our projected median annual HIV surveillance cost per health department ranged from $210,600 in low-HIV burden sites to $1,835,000 in high-HIV burden sites.

Conclusions

Our analysis shows that a systematic approach to costing HIV surveillance at the health department level is feasible. For HIV surveillance, a substantial portion of total surveillance costs is attributable to maintaining established cases.An estimated 1.2 million people aged 13 years and older are living with human immunodeficiency virus (HIV) in the United States, and about 47,500 people are infected with the virus each year.^1,2 A recent HIV surveillance report shows that the number of people living with HIV increased by 8% from 2006 through 2009.³ The U.S. Centers for Disease Control and Prevention (CDC) has developed an HIV surveillance system for collecting, analyzing, and disseminating accurate information on the number of people with new HIV diagnoses (new cases) and those living with HIV infection (established cases).^4,5 Access to timely and high-quality surveillance data is essential to detect trends in the HIV burden and develop appropriate prevention and control measures.^4,6,7 The U.S. Department of Health and Human Services has closely aligned the $16 billion it spent in 2010 on HIV care, treatment, and prevention with the number of reported HIV cases in each state.⁸ HIV case surveillance additionally guides the implementation of test-and-treat prevention strategies that require data on timing of diagnosis, entry into and retention in care, and viral load (VL) suppression.^8–10 The Institute of Medicine recently identified HIV case surveillance as one of the data collection systems that could be used to monitor progress in achieving National HIV/AIDS Strategy goals.^11,12The purpose of this analysis was to estimate the economic cost to health departments to conduct high-quality HIV case surveillance, where high quality is defined as meeting or exceeding CDC data quality standards regarding the completeness and timeliness of reporting diagnosed HIV cases and ascertaining duplicate cases and deaths.^6,7 We examined potential variation in costs across health departments based on differences in the number of new vs. established HIV cases, area-specific wages, and potential economies of scale. Results from the analysis could help inform surveillance funding allocation across health departments and enable health departments to more accurately assess their own costs attributable to new and established HIV cases.     

Acute hypophosphatasemia

Summary

The temporal evolution of a low serum alkaline phosphatase value may relate to its cause. Precipitous lowering of serum alkaline phosphatase below the lower range of normal is uncommon and may indicate severe physiologic stress and increased short-term mortality.

Introduction

The differential diagnosis of a low serum alkaline phosphatase (ALP) value (hypophosphatasemia) is wide ranging, anecdotal, and unfamiliar. The temporal evolution of hypophosphatasemia may relate to its cause. The purpose of this study is to report conditions and circumstances associated with precipitous lowering of serum ALP below the lower range of normal.

Methods

Marshfield Clinic IRB approved use of their electronic medical record to search for subjects with at least two serum ALP values ≤40 U/L (normal 40–125 U/L). When the temporal evolution of the qualifying ALP values indicated a precipitous lowering from usually normal serum ALP values, the subject was deemed to have acute hypophosphatasemia. Thirty years of laboratory data and 10 years of clinical narrative were analyzed. Associated diagnoses, clinical circumstances, and short-term mortality were recorded.

Results

A total of 458,767 subjects had 2,584,051 serum ALP values, and 5,190 (1.1 %) subjects had at least two serum values ≤40 U/L. A detailed review of 1,276 subjects selected on the basis of their lowest ALP value and age identified 190 subjects with acute hypophosphatasemia. Acute hypophosphatasemia was recorded during periods of major trauma/surgery, multisystem failure, acute anemia, blood product transfusions (often massive), apheresis, hypomagnesemia, and acute caloric restriction. Twenty-eight subjects (15 %) died within 35 days of their nadir serum ALP.

Conclusion

Acute hypophosphatasemia is associated with profound illness or physiologic stress and followed by increased short-term mortality. The temporal evolution of hypophosphatasemia may relate to its cause.     

The impact of nanoparticles on the mucosal translocation and transport of GLP-1 across the intestinal epithelium

Glucagon like peptide-1 (GLP-1) is an incretin hormone that is in the pipeline for type 2 diabetes mellitus (T2DM) therapy. However, oral administration of GLP-1 is hindered by the harsh conditions of the gastrointestinal tract and poor bioavailability. In this study, three nanosystems composed by three different biomaterials (poly(lactide-co-glycolide) polymer (PLGA), Witepsol E85 lipid (solid lipid nanoparticles, SLN) and porous silicon (PSi) were developed and loaded with GLP-1 to study their permeability in vitro. All the nanoparticles presented a size of approximately 200 nm. The nanoparticles' interaction with the mucus and the intestinal cells were enhanced after coating with chitosan (CS). PSi nanosystems presented the best association efficiency (AE) and loading degree (LD), even though a high AE was also observed for PLGA nanoparticles and SLN. Among all the nanosystems, PLGA and PSi were the only nanoparticles able to sustain the release of GLP-1 in biological fluids when coated with CS. This characteristic was also maintained when the nanosystems were in contact with the intestinal Caco-2 and HT29-MTX cell monolayers. The CS-coated PSi nanoparticles showed the highest GLP-1 permeation across the intestinal in vitro models. In conclusion, PLGA + CS and PSi + CS are promising nanocarriers for the oral delivery of GLP-1.     

Temporal-controlled Release of Bovine Serum Albumin from Chitosan Nanoparticles: Effect on the Regulation of Alkaline Phosphatase Activity in Stem Cells from Apical Papilla

Introduction

The controlled delivery of bioactive molecules is crucial for the regulation of stem cell differentiation. In this study, we examined the effects of temporal-controlled release of bovine serum albumin (BSA) from chitosan nanoparticles (CSnp) to regulate the alkaline phosphatase activity (ALP) in stem cells from apical papilla (SCAP).

Methods

BSA-loaded CSnp were synthesized by 2 methods to achieve the variant temporal-controlled release: (1) the encapsulation technique (BSA-CSnpI) and (2) the adsorption technique (BSA-CSnpII). After characterization of the size, charge, and release kinetics, SCAP were cultured in the presence of these bioactive molecule–loaded nanoparticles. SCAP viability was analyzed at 1, 7, 14, 21, and 28 days, and ALP activity was analyzed every 7 days until 21 days to determine the effect of these bioactive molecule–releasing nanoparticles on the cytotoxicity and differentiation potential, respectively.

Results

BSA-CSnpI and BSA-CSnpII presented distinct in vitro release profiles of BSA in a time-controlled manner. Cell viability was significantly enhanced over time in the presence of BSA-CSnpI and BSA-CSnpII (P < .01), when compared with BSA nonloaded CSnp. ALP activity was significantly higher (P < .01) in the presence of BSA-CSnpI after 3 weeks than in BSA-CSnpII.

Conclusions

BSA-loaded CSnps were synthesized and characterized in this study. Based on the physical/chemical interaction of BSA with CSnp (encapsulation or surface adsorption), different time-controlled release profiles were observed that influenced the ALP activity of SCAP in vitro. This study highlighted the potential of temporal-controlled bioactive molecule release technology in the differentiation of stem cells in dentin pulp regeneration.     

The role of ghrelin and growth hormone secretagogues receptor on rat adipogenesis

Recent research progress indicates a close link between ghrelin, a natural ligand of GH secretagogues receptor (GHS-R), and both the metabolic balance and body composition. To clarify the involvement of ghrelin and GHS-R in the process of adipogenesis, we measured the expression of GHS-R and peroxisome proliferator-activated receptor gamma 2 (PPAR-gamma 2) mRNA in rat adipocytes using semiquantitative RT-PCR methods. The levels of GHS-R mRNA increased by up to 4-fold in adipose tissue from epididymal and parametrial regions as the rat aged from 4-20 wk and were significantly elevated during the differentiation of preadipocytes in vitro. Ghrelin (10(-8) M for 10 d) stimulated the activity of glycerol-3-phosphate dehydrogenase and the differentiation of rat preadipocytes in vitro. Ghrelin treatment also significantly increased the levels of PPAR-gamma 2 mRNA in primary cultured rat differentiated adipocytes. In addition, isoproterenol (10(-8) M, 40 min)-stimulated lipolysis was significantly reduced by simultaneous ghrelin treatment in a dose-dependent manner in vitro. In conclusion, the expression of GHS-R in rat adipocytes increases with the age and during adipogenesis. Ghrelin in vitro stimulates the differentiation of preadipocytes and antagonizes lipolysis. Ghrelin may therefore play an important role in the process of adipogenesis in rats.