Metformin-associated lactic acidosis and temporary ileostomy: a case report

Lactic acidosis is a well-known complication of the anti-hyperglycemic biguanide agent metformin, especially in peculiar but not rare clinical conditions. Attempts to reduce the incidence of this adverse reaction have been enforced by national agencies over the years. The Italian Medicines Agency recently released a safety recommendation on prescribing the drug and with regard to the existence of several conditions that contraindicate drug continuation, such as dehydration, infection, hypotension, surgery or hyperosmolar contrast agent infusion, but the recommendation does not mention the increased risk related to stoma. The present case report is, to our knowledge, the first in the literature of metformin-associated lactic acidosis in a patient with a recently created ileostomy and low anterior resection for rectal cancer. CASE PRESENTATION: A 70-year-old Caucasian man who had undergone low anterior resection with total mesorectal excision and temporary loop ileostomy creation at our institution returned to our department 30 days later because of nausea, vomiting, diffuse abdominal pain and anuria of about 24 hours' duration. During his physical examination, the patient appeared dehydrated and had tachypnea and a reduced level of consciousness. His laboratory tests showed that he had acute kidney injury and severe lactic acidosis. CONCLUSION: An ileostomy puts patients at high risk for output losses that can lead to dehydration and electrolyte abnormalities. The assessment of the losses through the stoma, especially the ileostomy, should be added to the recommendations issued by pharmacovigilance societies. The present clinical case illustrates the need for clinicians on surgical wards to carefully evaluate patients before resuming metformin therapy and to provide appropriate information at discharge to patients with type 2 diabetes mellitus who have undergone ileostomy. Furthermore, this case report highlights the increasing need for more training of general physicians regarding both surgical and internal medicine problems that may arise in the post-operative course after major surgery in patients with co-morbidities

Neuromesenchymal hamartoma of small bowel - an extremely rare entity: a case report

Neuromuscular and vascular hamartoma (NMVH) is a very rare stricturing condition of the small intestine, occurring focally and causing recurrent obstructive symptoms or occult chronic gastrointestinal bleeding. Salas et al. (Neuromesenchymal hamartoma of the small bowel. J Clin Gastroenterol. 1990, 12 (6): 705-9) proposed the term of "Neuromesenchymal hamartoma" for the cases of NMVH with participation of mesenchymal tissues

Solitary splenic metastasis of squamous lung cancer: a case report

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A Novel Xenogeneic Co-Culture System to Examine Neuronal Differentiation Capability of Various Adult Human Stem Cells

Background: Targeted differentiation of stem cells is mainly achieved by the sequential administration of defined growth factors and cytokines, although these approaches are quite artificial, cost-intensive and time-consuming. We now present a simple xenogeneic rat brain co-culture system which supports neuronal differentiation of adult human stem cells under more in vivo-like conditions. Methods and Findings: This system was applied to well-characterized stem cell populations isolated from human skin, parotid gland and pancreas. In addition to general multi-lineage differentiation potential, these cells tend to differentiate spontaneously into neuronal cell types in vitro and are thus ideal candidates for the introduced co-culture system. Consequently, after two days of co-culture up to 12% of the cells showed neuronal morphology and expressed corresponding markers on the mRNA and protein level. Additionally, growth factors with the ability to induce neuronal different iation in stem cells could be found in the media supernatants of the co-cultures. Conclusions: The co-culture system described here is suitable for testing neuronal differentiation capability of numerous types of stem cells. Especially in the case of human cells, it may be of clinical relevance for future cell-based therapeutic applications

Chemically-Induced RAT Mesenchymal Stem Cells Adopt Molecular Properties of Neuronal-Like Cells but Do Not Have Basic Neuronal Functional Properties

Induction of adult rat bone marrow mesenchymal stem cells (MSC) by means of chemical compounds (β-mercaptoethanol, dimethyl sulfoxide and butylated hydroxyanizole) has been proposed to lead to neuronal transdifferentiation, and this protocol has been broadly used by several laboratories worldwide. Only a few hours of MSC chemical induction using this protocol is sufficient for the acquisition of neuronal-like morphology and neuronal protein expression. However, given that cell death is abundant, we hypothesize that, rather than true neuronal differentiation, this particular protocol leads to cellular toxic effects. We confirm that the induced cells with neuronal-like morphology positively stained for NF-200, S100, β-tubulin III, NSE and MAP-2 proteins. However, the morphological and molecular changes after chemical induction are also associated with an increase in the apoptosis of over 50% of the plated cells after 24 h. Moreover, increased intracellular cysteine after treatment indicates an impairment of redox circuitry during chemical induction, and in vitro electrophysiological recordings (patch-clamp) of the chemically induced MSC did not indicate neuronal properties as these cells do not exhibit Na+ or K+ currents and do not fire action potentials. Our findings suggest that a disruption of redox circuitry plays an important role in this specific chemical induction protocol, which might result in cytoskeletal alterations and loss of functional ion-gated channels followed by cell death. Despite the neuronal-like morphology and neural protein expression, induced rat bone marrow MSC do not have basic functional neuronal properties, although it is still plausible that other methods of induction and/or sources of MSC can achieve a successful neuronal differentiation in vitro