A multicenter study of total pancreatectomy with islet autotransplantation (TPIAT): POST (Prospective Observational Study of TPIAT)

Background/objectives

Total pancreatectomy with islet autotransplantation (TPIAT) is considered for managing chronic pancreatitis in selected patients when medical and endoscopic interventions have not provided adequate relief from debilitating pain. Although more centers are performing TPIAT, we lack large, multi-center studies to guide decisions about selecting candidates for and timing of TPIAT.

Reprogramming of murine and human somatic cells using a single polycistronic vector

Directed reprogramming of somatic cells by defined factors provides a novel method for the generation of patient-specific stem cells with the potential to bypass both the practical and ethical concerns associated with somatic cell nuclear transfer (SCNT) and human embryonic stem (hES) cells. Although the generation of induced pluripotent stem (iPS) cells has proven a robust technology in mouse and human, a major impediment to the use of iPS cells for therapeutic purposes has been the viral-based delivery of the reprogramming factors because multiple proviral integrations pose the danger of insertional mutagenesis. Here we report a novel approach to reduce the number of viruses necessary to reprogram somatic cells by delivering reprogramming factors in a single virus using 2A “self-cleaving” peptides, which support efficient polycistronic expression from a single promoter. We find that up to four reprogramming factors (Oct4, Sox2, Klf4, and c-Myc) can be expressed from a single virus to generate iPS cells in both embryonic and adult somatic mouse cells and we show that a single proviral copy is sufficient to generate iPS cells from mouse embryonic fibroblasts. In addition we have generated human induced pluripotent stem (hiPS) cell lines from human keratinocytes, demonstrating that a single polycistronic virus can reprogram human somatic cells.     

Investigating the disposal of expired and unused medication in Riyadh,Saudi Arabia: a cross-sectional study

Background Improper disposal of medication has several possible consequences such as childhood poisoning, environmental pollution, a negative impact on wildlife, and antibiotic resistance. The number of studies conducted to characterize pharmaceutical disposal practices is limited, particularly in the Middle East. Objective The aim of this cross-sectional study was to examine the behaviour of individuals with respect to the disposal of expired and unused medications. Furthermore, we aimed to identify the best methods of education regarding appropriate, safe disposal of medication. Setting The study was carried out in King Khalid University Hospital (KKUH), and King Saud University (KSU), during a 3-month period from February 2015 to April 2015. Method Twelve hundred patients were randomly selected from KKUH and KSU. Participants were invited to complete paper-based questionnaire with self enumeration. Pilot testing was conducted and involved 50 randomly selected participants. Main outcome measures The proportion of expired medications present in the home and their therapeutic groups, disposal methods of expired and unused medications, and preferred educational methods regarding safe and proper disposing of medications. Results A substantial proportion (79.15 %) of respondents disposed of unwanted medication via household waste, while a small proportion (1.70 %) returned unwanted medication to a pharmacy. Although currently practised disposal methods are undoubtedly unsuitable, 70.20 % of respondents considered finding appropriate, safe methods via which to dispose of unwanted medication their responsibility, and 78.6 % expressed an interest in receiving information concerning the correct disposal of unwanted medication. Conclusion We have demonstrated that a low percentage of respondents have ever received information regarding correct medication disposal. Moreover, the results have shown that over half of the respondents store antibiotics in their households. Additionally, respondents weren’t aware of the consequences of keeping expired medication at home. It is quite clear that the awareness of proper and safe drug disposal among the Saudi population is quite low making it a priority of concerned authorities to implement educational programs.     

Preoperative ERCP has no impact on islet yield following total pancreatectomy and islet autotransplantation (TPIAT): Results from the Prospective Observational Study of TPIAT (POST) cohort

Background and aimsMany patients undergoing total pancreatectomy with islet autotransplant (TPIAT) for severe, refractory chronic pancreatitis or recurrent acute pancreatitis have a history of endoscopic retrograde cholangiopancreatography (ERCP). Using data from the multicenter POST (Prospective Observational Study of TPIAT) cohort, we aimed to determine clinical characteristics associated with ERCP and the effect of ERCP on islet yield.MethodsUsing data from 230 participants (11 centers), demographics, pancreatitis history, and imaging features were tested for association with ERCP procedures. Logistic and linear regression were used to assess association of islet yield measures with having any pre-operative ERCPs and with the number of ERCPs, adjusting for confounders.Results175 (76%) underwent ERCPs [median number of ERCPs (IQR) 2 (1-4). ERCP was more common in those with obstructed pancreatic duct (p = 0.0009), pancreas divisum (p = 0.0009), prior pancreatic surgery (p = 0.005), and longer disease duration (p = 0.004). A greater number of ERCPs was associated with disease duration (p < 0.0001), obstructed pancreatic duct (p = 0.006), and prior pancreatic surgery (p = 0.006) and increased risk for positive islet culture (p < 0.0001). Mean total IEQ/kg with vs. without prior ERCP were 4145 (95% CI 3621-4669) vs. 3476 (95% CI 2521-4431) respectively (p = 0.23). Adjusting for confounders, islet yield was not significantly associated with prior ERCP, number of ERCPs, biliary or pancreatic sphincterotomy or stent placement.ConclusionsERCP did not appear to adversely impact islet yield. When indicated, ERCP need not be withheld to optimize islet yield but the risk-benefit ratio of ERCP should be considered given its potential harms, including risk for excessive delay in TPIAT.     

Topical Moltkia coerulea hydroethanolic extract accelerates the repairof excision wound in a rat model

Purpose: To evaluate the effect of a hydroethanolic extract of Moltkia coerulea ointment (MCO) on the healing of excision wound in a rat model. Methods: Circular surgical full thickness excision wound, with 314 mm2 size, was induced in the anterior-dorsal side of each rat. Three different doses of MCO (1%, 3% and 6%) were administrated. On Day 3, 7, 14 and 21, the tissue was sampled and immune cells, fibroblasts and fibrocytes distribution per one mm2 of wound area, collagen density and re-epithelialization were analyzed. Moreover, the total flavnoid, phenols and anti-oxidant potential of the MCO were evaluated. Ultimately, the percentage of wound contraction in different groups was compared with each other. Results: Hydroethanolic extract of MCO significantly (p<0.05) increased wound contraction percentage. The animals in medium and high dose MCO-treated groups exhibited remarkably (p<0.05) higher fibroblast and fibrocyte distribution and significantly (p<0.05) lower immune cells infiltration. On Day 7 after injury, MCO up-regulated neovascularization in a dose-dependent way. Conclusion: Our data showed that MCO shortened the inflammation phase by provoking the fibroblast proliferation. Moreover, MCO promoted the healing process by up-regulating the angiogenesis and provoking the structural cells proliferation as well as increasing the collagen synthesis, cross-linking, and deposition.     

Glutathione-dependent and -independent oxidative stress-control mechanisms distinguish normal human mammary epithelial cell subsets

Mechanisms that control the levels and activities of reactive oxygen species (ROS) in normal human mammary cells are poorly understood. We show that purified normal human basal mammary epithelial cells maintain low levels of ROS primarily by a glutathione-dependent but inefficient antioxidant mechanism that uses mitochondrial glutathione peroxidase 2. In contrast, the matching purified luminal progenitor cells contain higher levels of ROS, multiple glutathione-independent antioxidants and oxidative nucleotide damage-controlling proteins and consume O₂ at a higher rate. The luminal progenitor cells are more resistant to glutathione depletion than the basal cells, including those with in vivo and in vitro proliferation and differentiation activity. The luminal progenitors also are more resistant to H₂O₂ or ionizing radiation. Importantly, even freshly isolated “steady-state” normal luminal progenitors show elevated levels of unrepaired oxidative DNA damage. Distinct ROS control mechanisms operating in different subsets of normal human mammary cells could have differentiation state-specific functions and long-term consequences.Cellular synthesis of different reactive oxygen species (ROS) results primarily from the incomplete reduction of molecular oxygen in mitochondria to generate free radical superoxide anions. ROS also are produced when cells are exposed to different environmental sources of oxidative stressors, including ionizing radiation. Together, these regulate many normal cellular processes and also contribute to DNA damage, tumorigenesis, and cell death (1–3).In mice, the inner layer of “luminal” epithelial cells of the normal adult mammary gland have been found to contain higher levels of ROS than the outer “basal” layer of epithelial cells (4). The basis for these differences in ROS levels in the two cell types has been attributed to differences in their content of mitochondria; however, their stress response mechanisms have not been defined. Even less is known about ROS levels and their control in the normal adult human mammary gland, which consists of a similar continuous bilayered epithelial network of ducts and terminal alveolae. MCF10A cells are an immortal but nontumorigenic human mammary cell line that, when grown in 3D Matrigel cultures, generates multilayered spheres in which a lumen forms owing to the acquisition of lethal levels of ROS by the inner cells (5). These studies have suggested that ROS regulation plays an important role in the structural morphogenesis and homeostasis of normal adult human mammary tissue.Here we report the results of experiments designed to investigate the levels of ROS and their control in highly purified populations of viable luminal progenitors (LPs) and basal cells (BCs) isolated from normal human breast tissue (6–8). Our results confirm the different levels of ROS identified in the corresponding subsets of mouse mammary cells and further characterize the distinct antioxidant mechanisms operative in the human cells and their associated differential sensitivity to treatments that elevate ROS levels.