Language testing during awake "anesthesia" in a bilingual patient with brain lesion adjacent to Wernicke's area

Awake "anesthesia" is the preferable anesthetic approach for neurosurgical procedures that require intraoperative localization of eloquent brain areas. We describe intraoperative inducible selective English aphasia in a bilingual (English and Italian) patient undergoing awake anesthesia for excision of a brain lesion adjacent to Wernicke's area with no postoperative neurological sequelae. We discuss the importance of intraoperative brain mapping and intraoperative language testing in bilingual patients to prevent iatrogenic-related morbidity. Copyright © 2011 International Anesthesia Research Society

Neuroprotective effects of intravenous anesthetics: a new critical perspective.

Perioperative cerebral damage can result in various clinical sequela ranging from minor neurocognitive deficits to catastrophic neurological morbidity with permanent impairment and death. The goal of neuroprotective treatments is to reduce the clinical effects of cerebral damage through two major mechanisms: increased tolerance of neurological tissue to ischemia and changes in intra-cellular responses to energy supply deprivation. In this review, we present the clinical evidence of intravenous anesthetics on perioperative neuroprotection, and we also provide a critical perspective for future studies. The neuroprotective efficacy of the intravenous anesthetics thiopental, propofol and etomidate is unproven. Lidocaine may be neuroprotective in non-diabetic patients who have undergoing cardiac surgery with cardiopulmonary bypass (CBP) or with a 48-hour infusion, but conclusive data are lacking. There are several limitations of clinical studies that evaluate postoperative cognitive dysfunction (POCD), including difficulties in identifying patients at high-risk and a lack of consensus for defining the "gold-standard" neuropsychological testing. Although a battery of neurocognitive tests remains the primary method for diagnosing POCD, recent evidence suggests a role for novel biomarkers and neuroimaging to preemptively identify patients more susceptible to cognitive decline in the perioperative period. Current evidence, while inconclusive, suggest that intravenous anesthetics may be both neuroprotective and neurotoxic in the perioperative period. A critical analysis on data recorded from randomized control trials (RCTs) is essential in identifying patients who may benefit or be harmed by a particular anesthetic. RCTs will also contribute to defining methodologies for future studies on the neuroprotective effects of intravenous anesthetics

Daptomycin efficacy in the central nervous system of a patient with disseminated methicillin-resistant Staphylococcus aureus infection: a case report

<p>Abstract</p> <p>Introduction</p> <p><it>Staphylococcus aureus</it> has emerged as a major nosocomial pathogen in the last decades and also represents the second most common pathogen isolated from patients in outpatient settings. Although methicillin-resistant <it>S.aureus</it> infections were traditionally limited to hospitals, community-associated cases of methicillin-resistant <it>S.aureus</it> infections have been reported. In our case, we observed an unexpected event during treatment.</p> <p>Case presentation</p> <p>A 60-year-old Caucasian man developed fever and multiple muscle and brain abscesses caused by Panton-Valentine leukocidin-negative community-associated methicillin-resistant <it>S. aureus</it>.</p> <p>Conclusion</p> <p>Although our patient was given antimicrobials active against the isolated methicillin-resistant <it>S. aureus</it> strain, it was only after the introduction of daptomycin that his skin, soft tissue and muscle lesions and also brain manifestations improved.</p

Pyrazole-based inhibitors of enhancer of zeste homologue 2 induce apoptosis and autophagy in cancer cells

Novel pyrazole-based EZH2 inhibitors have been prepared through a molecular pruning approach from known inhibitors bearing a bicyclic moiety as a central scaffold. The hit compound 1o (N-((4,6-dimethyl-2-oxo-1,2-dihy-dropyridin-3-yl)methyl)-5-methyl-1-phenyl-1H-pyrazole-4-carboxamide) showed low micromolar EZH2/PRC2 inhibition and high selectivity towards a panel of other methyltransferases. Moreover, 1o displayed cell growth arrest in breast MDA-MB231, leukaemia K562, and neuroblastoma SK-N-BE cancer cells joined to reduction of H3K27me3 levels and induction of apoptosis and autophagy

Reproductive Traits of an Invasive Alien Population of Grey Squirrel (Sciurus carolinensis) in Central Italy

The reproductive cycle of an invasive alien Italian grey squirrel population was studied to understand its adaptation and limit its spread, in order to conserve the autochthonous red squirrel. Female and male genital traits were evaluated throughout the reproductive cycle, including the ovary, uterus, testicle, epididymis, seminiferous tubule morphometry, and germinative epithelium histology. Moreover, individual female fecundity was determined by counting uterine scars. Ovary width and uterus weight, length, and width reached their highest values in the luteal and pregnancy phases. On conducting a histological evaluation of the testicular germinal epithelium, four morphotypes related to the different reproductive phases of the male squirrels were identified: immature, pubertal, spermatogenesis, and regressive. Testicle and epididymis weights and seminiferous tubule diameters reached their largest values during spermatogenesis. Uterine scar analysis showed that 69% of the females had given birth to one or two litters, while 31% had no uterine scars. Litters were larger in the first breeding period than in the second; annual fecundity was 4.52 &plusmn; 1.88 uterine scars/female. Umbrian grey squirrels have adapted to their non-native range, showing two annual mating periods at times similar to those in their native range, and high reproductive success

Design of first-in-class dual EZH2/HDAC inhibitor: biochemical activity and biological evaluation in cancer cells

Since the histone modifying enzymes EZH2 and HDACs control a number of epigenetic-dependent carcinogenic pathways, we designed the first-in-class dual EZH2/HDAC inhibitor 5 displaying (sub)micromolar inhibition against both targets. When tested in several cancer cell lines, the hybrid 5 impaired cell viability at low micromolar level and in leukemia U937 and rhabdomyosarcoma RH4 cells provided G1 arrest, apoptotic induction, and increased differentiation, associated with an increase of acetyl-H3 and acetyl-α-tubulin and a decrease of H3K27me3 levels. In glioblastoma U87 cells, 5 hampered epithelial to mesenchymal transition by increasing the E-cadherin expression, thus proposing itself as a useful candidate for anticancer therapy

The histone methyltransferase EZH2 as a druggable target in SHH medulloblastoma cancer stem cells

The histone methyltransferase EZH2 plays a role in maintenance of the stem component of cancer, and its overexpression and/or mutation typically drives tumor aggressiveness, drug resistance and patients’ poor prognosis. In this study, we use mouse and human medulloblastoma stem-like cells belonging to the Sonic Hedgehog subgroup (SHH MB-SLCs) and demonstrate that genetic suppression of EZH2 reduces the level of its histone mark H3K27me3 and lowers proliferation and self-renewal. We designed an EZH2 inhibitor (EZH2i) as a simplified analog of EPZ005687 and GSK2816126, MC3629, and we tested its biological activity in SHH MB-SLCs. Pharmacological inhibition of EZH2 impairs SHH MB cells proliferation and self-renewal, and induces apoptosis in vitro. Finally, we generated xenograft MB-SLCs orthotopic tumors in nude mice to test MC3629 in vivo. In treated mice, we observed impairment of tumor growth, together with induction of apoptosis and reduction of proliferation and stemness. Overall, these findings describe EZH2 as a druggable target in MB and provide insight into the biological activity of MC3629 as an EZH2i