Giant cystic brain metastasis from ovarian papillary serous adenocarcinoma: Case report and review of the literature

Background: Ovarian brain metastases represent a very rare occurrence and without treatment, prognosis is very poor, with a median survival of one month. We present a unique case of a patient affected by a giant cystic intracerebral metastasis (>7 cm) secondary to an ovarian papillary serous adenocarcinoma, along with a review of the literature regarding large cystic ovarian metastases and their management. Case description: A 49-years-old female patient was admitted to our institution because she presented progressive headache and altered consciousness. Brain computed tomography (CT) scan and magnetic resonance imaging (MRI) revealed the presence of a giant left frontal intracerebral cystic lesion. The patient underwent a surgical removal of an ovarian high-grade papillary serous adenocarcinoma three years before. We performed a left frontal craniotomy and microsurgical removal of the brain lesion, achieving a safe macroscopic total resection, thanks to intraoperative neurophysiological monitoring (IONM). The post-operative period was uneventful with a complete recovery. Post-operative brain MRI showed a complete removal of the lesion. Conclusions: The presence of a giant cystic metastasis with symptoms of intracranial hypertension needs a radical and safe surgical removal, along with the management of a multidisciplinary oncologic group. Keywords: Brain metastasis, Ovarian carcinoma, Cystic, Gian

The role of brain cholesterol and its oxidized products in Alzheimer's disease.

The human brain is the most cholesterol-rich organ harboring 25% of the total cholesterol pool of the whole body. Cholesterol present in the central nervous system (CNS) comes, almost entirely, from the endogenous synthesis, being circulating cholesterol unable to cross the blood-brain barrier (BBB). Astrocytes seem to be more active than neurons in this process. Neurons mostly depend on cholesterol delivery from nearby cells for axonal regeneration, neurite extension and synaptogenesis. Within the brain, cholesterol is transported by HDL-like lipoproteins associated to apoE which represents the main apolipoprotein in the CNS. Although CNS cholesterol content is largely independent of dietary intake or hepatic synthesis, a relationship between plasma cholesterol level and neurodegenerative disorders, such as Alzheimer's disease (AD), has often been reported. To this regard, alterations of cholesterol metabolism were suggested to be implicated in the etiology of AD and amyloid production in the brain. Therefore a special attention was dedicated to the study of the main factors controlling cholesterol metabolism in the brain. Brain cholesterol levels are tightly controlled: its excessive amount can be reduced through the conversion into the oxidized form of 24-S-hydroxycholesetrol (24-OH-C), which can reach the blood stream. In fact, the BBB is permeable to 24-OH-C as well as to 27-OH-C, another oxidized form of cholesterol mainly synthesized by non- neural cells. In this review, we summarize the main mechanisms regulating cholesterol homeostasis and review the recent advances on the role played by cholesterol and cholesterol oxidized products in AD. Moreover, we delineate possible pharmacological strategies to control AD progression by affecting cholesterol homeostasis

Solution conformation of a potent cyclic analogue of tuftsin: low- temperature nuclear magnetic resonance study in a cryoprotective mixture.

Tuftsin, a linear tetrapeptide (Thr-Lys-Pro-Arg), corresponding to the sequence 289-292 of the heavy chain of leukokinin, has been the object of intensive SAR studies during the past 30 years, owing to its numerous biological activities and to the possibility of generating a novel anticancer drug. A cyclic tuftsin analogue, c-[T-K-P-R-G], has biological activity 50 times higher than that of the parent linear peptide. Here we present a conformational study of c-[T-K-P-R-G] based on NMR data in a cryoprotective DMSO/water mixture. The preferred conformation is a type via turn centered on the K-P residues. The orientation of the side chains of the two basic residues (K and R) may represent the essential feature of the bioactive conformation of tuftsin. A possible role of tuftsin as a DNA binding motif is suggested by the similarity of the bioactive conformation of c-[T-K-P-R-G] and of the β-turn conformation proposed by Suzuki for the [T,S]-P-K-R motif

I dialetti: patrimoni culturali locali nella lingua (rivista di proietti dottorali in corso)

It describes, succinctly, six doctoral thesis projects on Lucan dialectology that are underway in the framework of the doctoral program Lingua, Testo e Forme della Scrittura: Analisi linguistica, Tradizioni retorico-letterarie e Aspetti antropologici (Dipartimento di Scienze Umane), in the University of Basilicata. All these theses are vinculate to the Linguistic Atlas of Basilicata project (A.L.Ba), and make us aware of extraordinary diversity and richness of Lucan spoken, and its asset value to be preserved

Mitochondrial and Nuclear DNA Variants in Amyotrophic Lateral Sclerosis: Enrichment in the Mitochondrial Control Region and Sirtuin Pathway Genes in Spinal Cord Tissue

Amyotrophic Lateral Sclerosis (ALS) is a progressive disease with prevalent mitochondrial dysfunctions affecting both upper and lower motor neurons in the motor cortex, brainstem, and spinal cord. Despite mitochondria having their own genome (mtDNA), in humans, most mitochondrial genes are encoded by the nuclear genome (nDNA). Our study aimed to simultaneously screen for nDNA and mtDNA genomes to assess for specific variant enrichment in ALS compared to control tissues. Here, we analysed whole exome (WES) and whole genome (WGS) sequencing data from spinal cord tissues, respectively, of 6 and 12 human donors. A total of 31,257 and 301,241 variants in nuclear-encoded mitochondrial genes were identified from WES and WGS, respectively, while mtDNA reads accounted for 73 and 332 variants. Despite technical differences, both datasets consistently revealed a specific enrichment of variants in the mitochondrial Control Region (CR) and in several of these genes directly associated with mitochondrial dynamics or with Sirtuin pathway genes within ALS tissues. Overall, our data support the hypothesis of a variant burden in specific genes, highlighting potential actionable targets for therapeutic interventions in ALS

Naphtho[1,2-d]isothiazole Acetic Acid Derivatives as a Novel Class of Selective Aldose Reductase Inhibitors

Acetic acid derivatives of naphtho[1,2-d]isothiazole (NiT) were synthesized and tested as novel aldose reductase (ALR2) inhibitors. The parent compound 11 exhibited a fair inhibitory activity (IC50 = 10 μM), which was enhanced by 2 orders of magnitude by introducing a second carboxylic group at position 4 (13 and 14: IC50 = 0.55 and 0.14 μM, respectively). Substitution of the acetic acid function with an apolar group gave inactive (29) or poorly active (25, 26, 30) compounds, thus demonstrating that the 2-acetic group is involved in the enzyme pharmacophoric recognition while the 4-carboxylic moiety has only an accessory role. The potent compounds 11, 13, 14, 26 all proved to be selective for ALR2, since none of them inhibited aldehyde reductase, sorbitol dehydrogenase, or glutathione reductase. The isopropyl ester 31, a prodrug of 14, was found to be effective in preventing cataract development in severely galactosemic rats, when administered as an eyedrop solution. The theoretical binding mode of 13 and 14, obtained by docking simulations into the ALR2 crystal structure, was fully consistent with the structure-activity relationships in the NiT serie

Novel, Highly Potent Adenosine Deaminase Inhibitors Containing the Pyrazolo[3,4-d]pyrimidine Ring System. Synhesis, Structure-Activity Relationships, and Molecular Modeling Studies

This study reports the synthesis of a number of 1- and 2-alkyl derivatives of the 4-aminopyrazolo[3,4-d]pyrimidine (APP) nucleus and their evaluation as inhibitors of ADA from bovine spleen. The 2-substituted aminopyrazolopyrimidines proved to be potent inhibitors, most of them exhibiting Ki values in the nanomolar/subnanomolar range. In this series the inhibitory activity is enhanced with the increase in length of the alkyl chain, reaching a maximum with the n-decyl substituent. Insertion of a 2′-hydroxy group in the ra-decyl chain gave 3k, whose (R)-isomer displayed the highest inhibitory potency of the series (Ki 0.053 nM), showing an activity 2 orders of magnitude higher than that of (+)-EHNA (Ki 1.14 nM), which was taken as the reference standard. Docking simulations of aminopyrazolopyrimidines into the ADA binding site were also performed, to rationalize the structure-activity relationships of this class of inhibitor