Cortical laminar necrosis following myocardial infarction

The cortical laminar necrosis (CLN) is a permanent injury characterized by the selective delayed necrosis of the cerebral cortex, mainly of the third layer, and usually greater in the depths and sides of the sulci than over the crest of the gyri. The damage involves all cellular components – either neurons, glia cells and blood vessels – and results in a focal cortical band of pan-necrosis detectable in late sub-acute or chronic stages of reduced energy supply to the brain. The CLN has been described in different conditions as hypoxia, hypoglycemia and status epilepticus. At brain CT or MR scans it appears with pathognomonic highly hyperdense or T1-hyperintense lesions following the gyral anatomy of the cerebral cortex. We reported a case of CLN associated to myocardial infarct and discussed the underlying mechanisms

Alu insertion profiling: Array-based methods to detect Alu insertions in the human genome

Abstract The analysis of the genetic variability associated to Alu sequences was hampered by the absence of genome-wide methodologies able to efficiently detect new polymorphisms/mutations among these repetitive elements. Here we describe two Alu insertion profiling (AIP) methods based on the hybridization of Alu -flanking genomic fragments on tiling microarrays. Protocols are designed to preferentially detect active Alu subfamilies. We tested AIP methods by analyzing chromosomes 1 and 6 in two genomic samples. In genomic regions covered by array-features, with a sensitivity of 2% (AIP1) − 4% (AIP2) and 5% (AIP1) − 8% (AIP2) for the old J and S Alu lineages respectively, we obtained a sensitivity of 67% (AIP1) − 90% (AIP2) for the young Ya subfamily. Among the loci showing sample-to-sample differences, 5 (AIP1) − 8 (AIP2) were associated to known Alu polymorphisms. Moreover, we were able to confirm by PCR and DNA sequencing 4 new intragenic Alu elements, polymorphic in 10 additional individuals

Lacosamide during pregnancy and breastfeeding

Background The epilepsy treatment during pregnancy represents a balance between teratogenic hazard and seizure control. The aim of the study was to evaluate the safety and efficacy of lacosamide (LCS) during pregnancy and breastfeeding. Methods Patients referred to our Epilepsy Center for pregnancy planning who became pregnant while taking LCS were prospectively followed-up. Data on seizure frequency, side effects, pregnancy course, delivery and breastfeeding, birth outcome, congenital malformation and development of newborns were collected. Results Three cases of maternal exposure to LCS were reported. Treatment with LCS was continued throughout pregnancy and breastfeeding at a median daily dose of 400mg. Lacosamide was used as monotherapy in two patients and as add-on treatment in one woman. Seizure frequency did not change throughout pregnancy and two subjects remained seizure free. The median gestational age at delivery was 39 weeks. The median Apgar scores at 1 and 5min were 9 and 10, respectively; no major or minor congenital malformations were observed in the offspring. Normal developmental milestone were reached by all new-borns. Conclusions Worldwide pregnancy registries have provided consistent and increasing information about the efficacy and safety of the older antiepileptic drugs during gestation, while data are lacking for many of the newer generations. These cases could suggest a good level of efficacy and safety for LCS throughout pregnancy and breastfeeding and argue against teratogenic or toxic potentialities

Circulating γδ T cells in young/adult and old patients with cutaneous primary melanoma

BACKGROUND: In a previous study we demonstrated the existence of numerical and functional alterations of γδ T cells in healthy elderly. Recently, we analysed the involvement of γδ T lymphocytes in malignant melanoma, describing a lower frequency of circulating γδ T cells, an altered pattern of cytokine production, and an impaired in vitro expansion of these cells in primary cutaneous melanoma patients. METHODS: In this study we investigated the existence of numerical and functional alterations of circulating γδ T cells in young/adult and old melanoma patients, comparing the data obtained with age-matched healthy subjects. RESULTS: We demonstrated that the number of circulating γδ(+ )T cells was significantly and similarly reduced in young/adult and old melanoma patients and in old healthy subjects in comparison with young healthy donors. The decrease was due to a reduction of Vδ2 T cells whereas the number of Vδ1 T cells was not affected. A higher percentage of γδ(+ )T cells producing TNF-α was found in old healthy donors, whereas a reduced number of TNF-α-producing γδ(+ )T cells was present in melanoma patients independently by age. No significant difference was observed in IFN-γ production. After a 10-day in vitro culture, both the percentage and the expansion index of γδ T cells, and in particular of Vδ2 subset, were significantly and similarly reduced both in young/adult and old melanoma patients, and in healthy aged people, in comparison with young/adult healthy subjects. CONCLUSIONS: Our study demonstrates that the numerical and functional impairment of γδ T cells found in melanoma patients is not correlated with age and that it has characteristics very similar to the alterations of γδ T cells found in old healthy subjects. We suggest that a similar impairment of γδ T cell population may be related to the increased susceptibility to tumors present in the elderly as well as in the pathogenesis of malignant melanoma

Elevated Blood Pressure in the Acute Phase of Stroke and the Role of Angiotensin Receptor Blockers

Raised blood pressure (BP) is common after stroke but its causes, effects, and management still remain uncertain. We performed a systematic review of randomized controlled trials that investigated the effects of the angiotensin receptor blockers (ARBs) administered in the acute phase (≤72 hours) of stroke on death and dependency. Trials were identified from searching three electronic databases (Medline, Cochrane Library and Web of Science Database). Three trials involving 3728 patients were included. Significant difference in BP values between treatment and placebo was found in two studies. No effect of the treatment was seen on dependency, death and vascular events at one, three or six months; the cumulative mortality and the number of vascular events at 12 months differed significantly in favour of treatment in one small trial which stopped prematurely. Evidence raises doubts over the hypothesis of a specific effect of ARBs on short- and medium-term outcomes of stroke. It is not possible to rule out that different drugs might have different effects. Further trials are desirable to clarify whether current findings are generalizable or there are subgroups of patients or different approaches to BP management for which a treatment benefit can be obtained

Paraoxonase-1 55 LL Genotype Is Associated with No ST-Elevation Myocardial Infarction and with High Levels of Myoglobin

It is well known that serum paraoxonase (PON1) plays an important role in the protection of LDL from oxidation. PON1 55 polymorphism is currently investigated for its possible involvement in cardiovascular diseases. The objective of our study is to verify if PON1 55 polymorphism is associated with risk of acute coronary syndrome (ACS) and with biochemical myocardial ischemia markers, such as troponin I, creatine kinase (CK)-MB, myoglobin, and C-reactive protein. We analysed PON1 55 polymorphism in a total of 440 elderly patients who underwent an ACS episode: 98 patients affected by unstable angina (UA), 207 AMI (acute myocardial infarction) patients affected by STEMI (ST elevation), and 135 AMI patients affected by NSTEMI (no ST elevation). We found that individuals carrying PON1 55 LL genotype are significantly more represented among AMI patients affected by NSTEMI; moreover, the patients carrying LL genotype showed significantly higher levels of myoglobin in comparison to LM + MM carriers patients. Our study suggests that PON1 55 polymorphism could play a role in the pathogenesis of cardiac ischemic damage. In particular, the significant association between PON1 55 LL genotype and the occurrence of a NSTEMI may contribute to improve the stratification of the cardiovascular risk within a population

Effects of the Infusion of 4% or 20% Human Serum Albumin on the Skeletal Muscle Microcirculation in Endotoxemic Rats

Sepsis-induced microcirculatory alterations contribute to tissue hypoxia and organ dysfunction. In addition to its plasma volume expanding activity, human serum albumin (HSA) has anti-oxidant and anti-inflammatory properties and may have a protective role in the microcirculation during sepsis. The concentration of HSA infused may influence these effects. We compared the microcirculatory effects of the infusion of 4% and 20% HSA in an experimental model of sepsis

SELECTIVE ASSOCIATIVE PHONAGNOSIA AFTER RIGHT ANTERIOR TEMPORAL STROKE

We report the case of a 48 year old men who developed a selective impairment in famous voice recognition after ischemic stroke in right subcortical structures (lenticular nucleus and head of the caudate) and right anterior temporal lobe. He underwent fibrinolytic treatment. During the following days he progressively recovered and was discharged without neurological focal sign. Patent foramen ovale was found. When he got back to his house he noticed that he was unable to recognize the voice of his favoured singers and needed to ask who was the singer to his relatives. Neuropsychological examination revealed a selective impairment in famous voice recognition in the absence of alteration of voice perception, face perception and famous face recognition. All other neuropsychological domains were spared. In particular language, memory and executive functions were intact. Neuroimaging carried out by means of PET and MRI revealed two small ischemic lesions in the right subcortical region, involving lenticular and caudate nuclei and in the right temporal pole. To our knowledge, this is the first case described in literature of a patient showing a selective associative phonagnosia after right anterior temporal stroke. The present case helps to clarify the brain circuits underlying famous voice recognition and adds evidence in favour of a right hemisphere involvement in processing knowledge of familiar voices. These findings are discussed in relation to current models of brain organization of person-specific and general semantic knowledge.

Identification and Characterization of Cancer Stem Cells from Head and Neck Squamous Cell Carcinoma Cell Lines

Background/Aims: Head and neck squamous cell carcinoma (HNSCC) ranks sixth worldwide for tumor-related mortality. A subpopulation of tumor cells, termed cancer stem cells (CSCs), has the ability to support cancer growth. Therefore, profiling CSC-enriched populations could be a reliable tool to study cancer biology. Methods: We performed phenotypic characterization of 7 HNSCC cell lines and evaluated the presence of CSCs. CSCs from Hep-2 cell line and HNSCC primary cultures were enriched through sphere formation and sphere-forming cells have been characterized both in vitro and in vivo. In addition, we investigated the expression levels of Nicotinamide N-methyltransferase (NNMT), an enzyme overexpressed in several malignancies. Results: CSC markers were markedly expressed in Hep-2 cell line, which was found to be highly tumorigenic. CSC-enriched populations displayed increased expression of CSC markers and a strong capability to form tumors in vivo. We also found an overexpression of CSC markers in tumor formed by CSC-enriched populations. Interestingly, NNMT levels were significantly higher in CSC-enriched populations compared with parental cells. Conclusion: Our study provides an useful procedure for CSC identification and enrichment in HNSCC. Moreover, results obtained seem to suggest that CSCs may represent a promising target for an anticancer therapy