Antidiabetic Potential of a Trimeric Anthranilic Acid Peptide Isolated from Malbranchea flocciformis.

Compound 3, a trimeric anthranilic acid peptide, and another three metabolites were isolated from an organic extract from the culture medium of Malbranchea flocciformis ATCC 34530. The chemical structure proposed previously for 3 was unequivocally assigned via synthesis and X-ray diffraction analysis. Tripeptide 3 showed insulinotropic properties by decreasing the postprandial peak in healthy and hyperglycemic mice. It also increased glucose-induced insulin secretion in INS-1E at 5 µM, specifically at higher glucose concentrations. These results revealed that 3 might act as an insulin sensitizer and a non-classical insulin secretagogue. Altogether, these findings are in harmony with the in vivo oral glucose tolerance test and acute oral hypoglycemic assay. Finally, the chemical composition of the extract was established by the Global Natural Products Social Molecular Network platform. Phylogenetic analysis using the internal transcribed spacer region revealed that M. flocciformis ATCC 34530 is related to the Malbrancheaceae.

Ambulatory non-convulsive status epilepticus evolving into a malignant form.

We retrospectively analysed the clinical characteristics, electroencephalogram (EEG) records, brain magnetic resonance imaging (MRI) scans, antiepileptic therapy and prognosis of a case series with ambulatory non-convulsive status epilepticus (NCSE) which evolved into a malignant form (mNCSE). mNCSE was defined as NCSE that continues or recurs five days or more after the onset of general anaesthesia, including those cases where NCSE recurs upon reduction or withdrawal of anaesthetic therapy. Four women and two men were studied. The mean age was 42.8 years (range: 19-63 years). Two of six patients had a previous diagnosis of epilepsy. Four patients died. Two patients had a good outcome with return to consciousness and activities of daily life, and one of these subjects developed temporal lobe epilepsy. In four patients, the cause of mNCSE was encephalitis. Clinical presentation was complex partial status epilepticus (CPSE) in three patients and generalised NCSE (GNCSE) in the other three. Two of the latter had encephalitis and one was diagnosed with progressive myoclonus epilepsy (PME) of Lafora type. The mean duration of the NCSE episode was 47.5 days (range: 9-139 days; SD: 53.1). In three patients, continuous or rhythmic focal epileptiform discharges were the EEG pattern at onset. In the other three, continuous rhythmic generalised spike-wave, polyspike-wave or sharp slow-wave complexes were observed. Antiepileptic treatment was heterogeneous and patients were treated with an average of 6.0 AEDs (range: 3-10; SD: 3.0). In summary, mNCSE is a severe epileptic condition that occurs often in the context of encephalitis or pre-existing epilepsy. Both CPSE and GNCSE may occur. Although high mortality is associated with mNCSE, some patients may survive with normal or good recovery.

New insight of molecular imaging into the atheroma biology: (18)F-fluoride PET/CT and 18F-FDG PET/CT of 3 carotid plaques in a symptomatic neurologic patient.

In a 75-year-old patient admitted with a middle cerebral artery stroke, a contrast-enhanced CT showed 3 atheroma plaques. Five days after the stroke, a F-fluoride PET/CT to evaluate calcification and, 24 hours later, a F-FDG PET/CT to evaluate inflammation were carried out. The different metabolic behavior of both radiotracers, showing different intensities and distribution in each plaque, may represent different phases of the atherogenesis and in combination could provide new information for the early identification of the carotid unstable plaque.

Nonconvulsive status epilepticus in adults: electroclinical differences between proper and comatose forms.

OBJECTIVE: Nonconvulsive status epilepticus (NCSE) represents an important percentage of status epilepticus in adults, but detailed studies of both NCSE proper and comatose NCSE are lacking. We retrospectively analyzed a prospectively collected series of 50 adult patients with a diagnosis of NCSE whose electroencephalograms (EEGs) have been interpreted for a period of 10 years by the same investigator. METHODS: Two groups, NCSE proper and comatose NCSE were considered. All clinical, EEGs, neuroimaging data, antiepileptic treatment and outcome were analyzed. RESULTS: Thirty-two patients (64%) had NCSE proper and 18 patients (36%) comatose NCSE. The mean age was 56 years (range 19-89 years). Fourteen (44%) were diagnosed with absence status epilepticus (ASE), one had simple partial status epilepticus (SPSE) and 17 (53%) had complex partial status epilepticus (CPSE). The mean episode duration (33.2±13.9 versus 60.6±34.0), mean number of antiepileptic drugs (AEDs) (1.46±0.5 versus 2.77±1.39) and neuroimaging anomalies (50% versus 16%) was significantly greater in the partial/focal NCSE proper subgroup than in the ASE subgroup. The mean age (56.0±19.9 versus 69.4±12.1), number of elderly individuals (46% versus 77%), mean duration of the episode (49.1±30.4 versus 153.3±142.6), mortality rate (6% versus 61%) and admission at ICU (18% versus 83%) was significantly higher in the comatose NCSE group than in the NCSE proper group (p<.05). Conversely, a previous history of chronic epilepsy was significantly more frequent (62% versus 5.6%) in the NCSE proper group. The mean duration of comatose NCSE was significantly greater in the surviving subgroup (102.5±29.1 versus 233.1±65.3; p<.05). CONCLUSIONS: Our study demonstrates that there are sufficient differences regarding age of onset, history of previous epilepsy, episode duration, mortality rate and clinical presentation between NCSE proper and comatose NCSE to recommend adoption in clinical practice. These results should be taken into account when developing future classifications and therapeutic trials on NCSE. SIGNIFICANCE: A distinction between NCSE proper (ambulatory forms of NCSE) and comatose NCSE is useful in the clinical practice and, therefore, it should taken in account in the design of future investigations on this heterogeneous epileptic condition.

Spontaneous cerebral calcific embolus from the aortic arch.

Spontaneous calcific embolism is an uncommon cause of stroke. In most cases calcified cardiac valves are the sources of the emboli although embolization of calcific material from the brachiocephalic trunk has also been described. We report a case of stroke attributable to spontaneous calcific emboli from the aortic arch in which migration of the emboli was observed along the middle cerebral artery following iv tPA.

Permanent dysphasia after status epilepticus: long-term follow-up in an elderly patient.

We report the long-term follow-up of an elderly patient who developed a permanent sensorimotor dysphasia after status epilepticus. Magnetic resonance imaging of the brain and magnetic resonance angiography failed to demonstrate structural cerebral damage; however, a fluorodeoxyglucose positron emission tomography scan revealed marked hypometabolism involving a large area in the left hemisphere and contralateral cerebellar cortex. Our case illustrates that permanent language dysfunction may occur after recurrent complex partial and secondarily generalized seizures.

Severe serotonin syndrome induced by mirtazapine monotherapy.

OBJECTIVE: To document a case of serotonin syndrome (SS) associated with mirtazapine monotherapy, review the previously reported cases of SS associated with this tetracyclic antidepressant, and discuss the possible pathogenic mechanisms leading to this serious adverse drug reaction. CASE SUMMARY: A 75-year-old man developed agitation, confusion, incoordination, and gait disturbance because of progressive rigidity. Mirtazapine had been started 8 days earlier to control major depression. Physical examination revealed diaphoresis, low-grade fever, hypertension, tachycardia, bilateral cogwheel rigidity, hyperreflexia, tremor, and myoclonus, symptoms and signs that are consistent with severe SS. DISCUSSION: A review of the cases of SS with implication of mirtazapine as the cause was performed. The possible pathogenic mechanisms leading to this adverse reaction in this patient are also discussed, and pathophysiologic hypotheses are formulated. CONCLUSIONS: Although mirtazapine offers clinicians a combination of strong efficacy and good safety, we suggest bearing SS in mind when prescribing this drug, especially in frail, elderly patients with underlying chronic conditions. In these patients, it might be more adequate to start mirtazapine therapy at a lower dose (<15 mg/d).