Acute metformin intoxication: 2012 experience of Emergency Departement of Lodi, Italy.

UNLABELLED: Background: Metformin is a biguanide antihyperglycemic agent that decreases insulin resistance. It is removed through renal mechanisms and its clearance is reduced in renal failure. Metformin ingestion should always be considered in the differential diagnosis of any patient with metabolic acidosis and increased lactate level. Hemodialysis and continuous veno-venous hemofiltration (CVVH) are both efficient methods to treat metformin intoxication and correct metabolic abnormalities. METHODS: Patient 1: A 63-year-old man with type 2 diabetes mellitus presented to emergency department (ED) of Lodi (Italy) for dyspnea. He also reported having diarrhea for 10 days. Initial investigations revealed metabolic acidosis with hyperlactatemia and hypoglycemia (54 mg/dL), metformin concentration was 41 µg/mL (normal value <4 µg/mL). His hemodynamic condition became rapidly unstable and hypotension worsened despite CVVH being performed. Death occurred in 24 h. Patient 2: A 76-year-old man with type 2 diabetes mellitus presented to ED of Lodi for dyspnea. He referred a recent surgery amputation of the left foot's fifth phalanx for osteomyelitis, in levofloxacin therapy. Initial investigations revealed metabolic acidosis with hyperlactatemia and severe hypoglycemia (20 mg/dL). Two hemodialysis sessions were performed with complete normalization of the serum concentration of metformin. RESULTS AND CONCLUSIONS: In our two cases the genesis of metformin intoxication was clear, powered by acute renal failure, but less obvious was the etiology of acute renal damage responsible for metformin accumulation. Damage due to renal hypoperfusion or the direct toxic effect of metformin should be considered. Additionally, for the second patient, we can also hypothesize that interstitial nephritis was exacerbated by levofloxacin.

Immunohistochemical expression of oncological proliferation markers in the hearts of rats during normal pregnancy.

AIM: Pregnancy is characterized by left ventricular hypertrophy that is potentially accounted for by cardiomyocyte proliferation, although no such evidence is currently available. This study investigates if the left ventricular mass (LVM) increase during pregnancy implies cell hyperplasia. MATERIALS & METHODS: In nonpregnant and late-pregnant rats, cardiac function and LVM were evaluated by MRI, and cardiomyocyte dimensions and proliferations were assessed quantitatively by morphometric analysis and immunohistochemistry using oncological markers (Ki67 and MCM2). RESULTS: In late-pregnant rats, LVM and cardiomyocyte area were greater. No mitotic figures were found nor was there any significant difference between groups in Ki67 expression. MCM2 expression was related to LVM. CONCLUSION: During pregnancy, rat cardiomyocytes undergo hypertrophy but not hyperplasia; the expression of MCM2, related to LVM, suggests it could be a marker of protein synthesis. The application of oncological markers to physiological contexts may provide insight into their role within the cell cycle.

Episodes of Fall Asleep During Day Time in an Elder Woman with Vascular Dementia: Impact on Cerebral Ischeamic Tolerance and Utility of ECG Holter Monitoring.

Here we report the case of an 86-year-old woman with advanced dementia addressed to our service for routinary ECG Holter Monitoring (EHM) for bradycardia in AV block type I. Several day-time episodes of fall-asleep while sitting had been previously reported by the nurse and generally attributed to the dementia itself, without taking into consideration the hypothesis of an AV block. The EHM reading reported several and often subsequent pauses (561), many of them critical, the longest lasting 15,9 s with no changes in clinical condition of the patient. The results of the EHM were reported to the physicians in charge for the patient and subsequently the woman was referred to the arrhythmology unit for pace-maker device implantation. Generalizing our experience, we suggest that advanced dementia, often associated with episodes of fall-asleep, could mask a conduction disturbance causing critical pauses with syncope; therefore we suggest screening those patients for possible arrhythmic disorders. Finally, we remark that in our patient the pauses weren't associated with a worsening of the patient as seen in the follow-up, and this fact supports the hypothesis that vascular dementia could increase cerebral ischaemic tolerance.

Experimental animal models of myocardial damage in regenerative medicine studies involving adult bone marrow derived stem cells: ethical and methodological implications.

Cardiac performance after myocardial infarction is compromised by ventricular remodeling, which represents a major cause of late infarct-related chronic heart failure and death. In recent years, the scientists' interest has focused on the hypothesis that the administration of bone marrow progenitors, following myocardial infarction, could ameliorate left ventricular remodeling by continuing to differentiate along the haematopoietic lineage. This approach has been developed minding to the consolidated use of transfusions to restore lost or depleted blood components and, therefore, as an enriched dose of various progenitors, generally autologous, injected peripherally or directly in the infarcted area. Since the safety of this therapy was not yet established, for ethical reasons pioneering researchers involved in these studies used animal models as surrogate of the human biologic system. Herein this hypothesis of therapy resulted in an increased use of living animals and in the reappraisal of models of myocardial damage with limited discussion on the theoretical basis of animal models applied to cell-based therapies. Recently, the European Union and its commission for surveillance of laboratory animals advanced a new proposal to restrict the use of living animals. This review will focus on the history of models utilization in biomedicine, with particular attention to animal models, and delineate an operative comparison between the two best known models of myocardial injury, namely coronary ligation and cryodamage, in the perspective of adult stem cell research applied to cardiovascular regenerative medicine.