Radiotherapeutic alternatives for previously irradiated recurrent gliomas

Re-irradiation for recurrent gliomas has been discussed controversially in the past. This was mainly due to only marginal palliation while being associated with a high risk for side effects using conventional radiotherapy

Biosynthesis of Polyamines in Mouse Brain: Effects of Methionine Sulfoximine and Adenosylhomocysteine

This study examines the consequences on cerebral polyamine biosynthesis of increases and decreases in cerebral methylation. Increases were elicited by administering the convulsant agent methionine sulfoximine (MSO) and decreases by elevating in vivo the cerebral levels of the methylation inhibitor S-adenosylhomocysteine. Following the intraventricular (i.vt.) administration of one of the two possible polyamine precursors, [1,4-14C]putrescine, the specific radioactivity (sra) of the newly formed [14C]spermidine remained unchanged. Conversely, after i.vt. L-[3,4-14C]methionine, the other polyamine precursor, significantly higher sra values for [14C]spermidine and [14C]spermine were recorded in the brains of the MSO-treated animals. [14C]S-adenosylmethionine in the brain of the MSO-treated animals was also more highly labeled following [1-14C]-methionine, indicating its accelerated formation relative to controls. We also investigated the effect of the administration of adenosine + homocysteine, a treatment that results in elevated brain adenosylhomocysteine levels, on polyamine biosynthesis from [3,4-14C]-methionine. The results of these experiments show both significantly lower sra values for [14C]spermidine and [14C]spermine and significantly higher than control endogenous methionine levels, a clear sign of the existence of a retardation in the conversion of methionine to polyamines under these conditions. In conclusion, the present study demonstrates that while interference with cerebral methylation results in significant alterations of the rate of formation of the methionine moiety of spermidine and spermine, it has no effect on the entry of the putrescine moiety into the two polyamine molecules

The biosynthesis of polyamines in the brain of audiogenic seizure-susceptible and -resistant deermice.

The biosynthesis of polyamines was investigated in the brains of the audiogenic seizure-susceptible (SS) mutant and the wild-type, seizure-resistant (SR) deermouse Peromyscus maniculatus bairdii. For this purpose a new, rapiti, and economical high pressure liquid chromatography (HPLC) procedure for the quantitation of putrescine, spermidine, and spermine was developed. Benzoyl derivatives of the polyamines, prepared from a crude brain supernatant, were ether extracted and, following removal of the ether, were separated and quantitated by HPLC. The high sensitivity of the method allows quantitation of putrescine in 50 mg and of spermidine and spermine, in as little as 2-2.5 mg, of brain tissue. No differences were found in endogenous levels of the 3 polyamines in brains of SS vs SR deermice. Using [14C]putrescine as a polyamine precursor, we found the specific radioactivity of spermidine to be lower in the SS than in the SR brains following a 1 h intraventricular (i.vt.) pulse. No such differences were noted if [3,4-14C]methionine was used as the polyamine precursor. To test whether the flux of methionine through the transmethylation pathway was also different in SS and SR deermouse brain, we administered [1-14C]methionine (i.vt.) (1 h pulse). Even though the brains of SS animals contained higher methionine and lower S-adenosyl-L-methionine (AdoMet) levels than the SR brains, the specific radioactivities of methionine and AdoMet were, respectively, lower and higher in SS compared to SR brains. The latter results are in agreement with our previous findings of an accelerated utilization of AdoMet in brains of Swiss-Webster mice following administration of the chemical convulsant L-methionine-d,1-suffoximine (MSO). Taken together, the data suggest that the SS condition, whether genetically determined (as in the SS deermouse) or chemically elicited (as after MSO), correlates positively with higher than normal rates of conversion of methionine to brain AdoMet and leads to an enhanced rate of utilization of AdoMet via the transmethylation pathway. Key Words: Seizure-sensitive-Seizure-resistant-deermice-Brain polyamines-Transmethylation-S-adenosyl-L- methionine-HPLC. Porta et al. The biosynthesis of polyamines in the brain of audiogenic seizure-susceptible and -resistant deermice

Association between subthalamic nucleus deep brain stimulation and weight gain: Results of a case–control study

•Patients with PD have been shown to lose weight over the course of their disease.•Weight gain has been reported in PD patients after deep brain stimulation (DBS).•In this study, PD cases gained weight while controls not undergoing DBS lost weight.•This weight gain may be normative and further prospective study is needed. To evaluate whether weight change in patients with Parkinson's disease (PD) is different in those undergoing deep brain stimulation (DBS) of the subthalamic nucleus (STN) compared to those not undergoing DBS. A retrospective case–control study was performed in PD patients who had undergone STN DBS (cases) compared to matched PD patients without DBS (controls). Demographic and clinical data including Unified Parkinson's Disease Rating Scale (UPDRS) motor scores were collected. Repeated measures mixed model regression was used to identify variables associated with weight gain. Thirty-five cases and 34 controls were identified. Baseline age, gender, diagnosis and weight were similar. Duration of diagnosis was longer in cases (6.3 vs 4.9 years, p=0.0015). At 21.3 months, cases gained 2.9kg (+4.65%) while controls lost 1.8kg (−3.05%, p<0.02). Postoperative UPDRS motor scores improved by 49% indicating surgical efficacy. Only younger age (p=0.0002) and DBS (p=0.008) were significantly associated with weight gain. In this case–control study, PD patients undergoing STN DBS experienced post-operative weight gain that was significantly different from the weight loss observed in non-DBS PD controls. Patients, especially overweight individuals, should be informed that STN DBS can result in weight gain