Studies of the halogenation of some substituted naphthalenes

A general survey of the reaction of electrophilic halogens with polynuclear aromatic substrates has led to the conclusion that in many cases addition may take place concurrently with substitution. This is important in understanding the mechanism of this kind of reaction, especially as to the sequences leading to the isolated products, which seem to represent an alternative fate of a common carbonium ionic intermediate. The addition of molecular chlorine to a number of simple naphthalene derivatives has, therefore, been investigated under a wide range of experimental conditions. The products of these reactions were isolated and char= acterised as far as possible, particularly by using column chromatography, proton magnetic resonance spectroscopy, and kinetic techniques. The chlorination of 1-, 2-, 1,2-, and 1,4-substitu= ted naphthalenes, with activating, deactivating, or mixed groups on the nucleus, gave products of substitution, accompanied mainly by tetrachlorides and acetoxytrichlo rides, whose structures and predominant conformations in solution have been elucidated. On the whole it is found that addition of chlorine always occurs on the ring to which substitution takes place in accordance with the rules governing electrophilic substitution. Of the six possible orientations of substituents in theresulting tetralin ring system, two forms clearly pre= dominate, having the atoms (or groups) added to the alicyclic ring according to a '-e-e-a' or a'-e-e-e' spatial orientation. The relative rates and products of alkaline dehy= drochlorination have also been studied and are those expected from the configurations of the individual pro= ducts examined, and throw some light on their possible modes of hydrogen chloride elimination.Finally, in discussing the reaction paths leading to the addition products, the results confirm the possibility that polar addition of chlorine can proceed both in the cis- and trans-sense; but, when heterolytic conditions are chosen, the former is a most frequent process that has usually been recognized.<p

Microglia Are Mediators of Borrelia burgdorferi–Induced Apoptosis in SH-SY5Y Neuronal Cells

Inflammation has long been implicated as a contributor to pathogenesis in many CNS illnesses, including Lyme neuroborreliosis. Borrelia burgdorferi is the spirochete that causes Lyme disease and it is known to potently induce the production of inflammatory mediators in a variety of cells. In experiments where B. burgdorferi was co-cultured in vitro with primary microglia, we observed robust expression and release of IL-6 and IL-8, CCL2 (MCP-1), CCL3 (MIP-1α), CCL4 (MIP-1β) and CCL5 (RANTES), but we detected no induction of microglial apoptosis. In contrast, SH-SY5Y (SY) neuroblastoma cells co-cultured with B. burgdorferi expressed negligible amounts of inflammatory mediators and also remained resistant to apoptosis. When SY cells were co-cultured with microglia and B. burgdorferi, significant neuronal apoptosis consistently occurred. Confocal microscopy imaging of these cell cultures stained for apoptosis and with cell type-specific markers confirmed that it was predominantly the SY cells that were dying. Microarray analysis demonstrated an intense microglia-mediated inflammatory response to B. burgdorferi including up-regulation in gene transcripts for TLR-2 and NFκβ. Surprisingly, a pathway that exhibited profound changes in regard to inflammatory signaling was triggering receptor expressed on myeloid cells-1 (TREM1). Significant transcript alterations in essential p53 pathway genes also occurred in SY cells cultured in the presence of microglia and B. burgdorferi, which indicated a shift from cell survival to preparation for apoptosis when compared to SY cells cultured in the presence of B. burgdorferi alone. Taken together, these findings indicate that B. burgdorferi is not directly toxic to SY cells; rather, these cells become distressed and die in the inflammatory surroundings generated by microglia through a bystander effect. If, as we hypothesized, neuronal apoptosis is the key pathogenic event in Lyme neuroborreliosis, then targeting microglial responses may be a significant therapeutic approach for the treatment of this form of Lyme disease

Safety and Efficacy of Eucaloric Very Low-Carb Diet (EVLCD) in Type 1 Diabetes: A One-Year Real-Life Retrospective Experience

A eucaloric very low carbohydrate diet (EVLCD) is a diet with a daily caloric intake equal to the total daily energy expenditure (TDEE) with a carbohydrate content of &lt;50 g/day. The literature on very low carbohydrate diets (VLCD) in type 1 diabetes (DM 1) is limited, although recently published scientific studies have highlighted their safety and efficacy in managing DM 1. In this retrospective analysis, we report the clinical data of 33 patients affected by DM 1 carrying out insulin therapy who switched voluntarily from their usual diet (high carb, low fat) to an EVLCD. Our aim is to evaluate the glycemic control, the amount of insulin needed in order to maintain glycemic control and safety of EVLCD. The switch improved glycemic control (mean glycated hemoglobin decreased from 8.3% to 6.8% (p &lt; 0.01). The number of patients who reached a glycated hemoglobin value of &lt;7% increased statistically from 12% to 57% (p &lt; 0.01), and there was a statistically significant decrease (p &lt; 0.01) in the units of daily insulin (from 36.7± 14.9 IU to 28.9 ±9.1 IU) A reduction from 54% to 24% in clinical level 2 hypoglycemia episodes was reported. No cases of severe hypoglycemia or ketoacidosis were observed. The results of the study support that EVLCD in DM 1 seems safe and effective when adopted under tight medical supervision

Effects of zonisamide as add-on therapy on sleep-wake cycle in focal epilepsy: a polysomnographic study

The purpose of this study was to evaluate the effects of zonisamide (ZNS) as adjunctive therapy on sleep-wake cycle and daytime somnolence in adult patients affected by focal epilepsy