Predictors of Weight Loss in Adults with Topiramate‐Treated Epilepsy

Objective: We examined predictors of weight loss with topiramate, an anticonvulsant associated with weight loss in adults. Research Methods and Procedures: In this uncontrolled, prospective clinical trial, topiramate was added to existing anticonvulsants in adults (40 to 110 kg) with partial‐onset seizures. Primary measurements were change from baseline weight after 3 months and 1 year in patients completing 1 year of topiramate treatment (N = 38). Physiological and metabolic measures were analyzed for correlation with weight loss during topiramate treatment. Results: In patients who completed 1 year of topiramate treatment, baseline weight was reduced in 82% at 3 months and in 86% at 1 year. Mean body weight was reduced 3.0 kg (3.9% of baseline) at 3 months and 5.9 kg (7.3%) at 1 year. In obese patients [body mass index (BMI) ≥ 30 kg/m²], mean weight loss was 4.2 kg (4.3%) at 3 months and 10.9 kg (11.0%) at 1 year. Weight loss was primarily caused by reduction in body fat mass. For all patients, weight loss at 3 months correlated most strongly with reduced caloric intake (p = 0.02). At 1 year, caloric intake had returned to baseline levels; weight loss correlated most strongly with higher baseline BMI (p = 0.0007). Discussion: Our results suggest that weight loss occurs in most adults treated with topiramate and is sustained for at least 1 year. Reduced caloric intake may account, in part, for weight loss during early treatment. The pattern of weight loss differs according to baseline BMI, with obese patients experiencing greater weight loss during continued therapy.     

Membranes as possible pacemakers of metabolism.

Basal metabolic rate (BMR) varies dramatically among vertebrate species, both (i) being several fold higher in the endothermic mammals and birds compared to the ectothermic reptiles, amphibians and fish, and (ii) being much greater, on a body mass basis, in small vertebrates compared to large vertebrates. These differences in whole animal BMR are also manifest at the cellular level with substantial contributions to basal metabolic activity from the maintenance of various trans-membrane gradients. The percentage contribution of various processes to basal metabolism is remarkably consistent between different vertebrates and when BMR varies, the components of metabolic activity vary in relative unison. Membrane composition also varies between vertebrates and the degree of polyunsaturation of membrane phospholipids is correlated with cellular metabolic activity. In general, the tissue phospholipids and thus membrane bilayers of endotherms are more polyunsaturated than those from similar-sized ectotherms. In mammals membrane polyunsaturation is allometrically related to body mass. We suggest that membranes can act as pacemakers for overall metabolic activity. We propose that such membrane polyunsaturation increases the molecular activity of many membrane-bound proteins and consequently some specific membrane leak-pump cycles and cellular metabolic activity. We hypothesize a possible mechanistic basis for this effect that is based on a greater transfer of energy during intermolecular collisions of membrane proteins with the unsaturated two carbon units (C=C) of polyunsaturates compared to the single carbon units of saturated acyl chains, as well as the more even distribution of such units throughout the depth of the bilayer when membranes contain polyunsaturated acyl chains compared to monounsaturated ones. The proposed pacemaker role of differences in membrane bilayer composition is briefly discussed with respect to the brain (and sensory cells), evolution of mammalian endothermic metabolism, and its clinical implications for humans.     

Intrinsically disordered Meningioma-1 stabilizes the BAF complex to cause AML

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Tierpsychologische Studien an Radnetzspinnen

Zusammenfassung Im Gegensatz zur Volkeltschen, auf situationsbedingte Komplexqualitäten zurückgreifenden Deutung des Verhaltens der Spinne gegenüber der Beute innerhalb und außerhalb des Netzes wird gezeigt, daß die Spinne in weitestem Maße durch den isolierten Vibrationsreiz zur Fanghandlung bestimmt wird.Analog wird ein ebenso isolierbarer Einzelreiz aufgewiesen, der das Feindverhalten bewirkt, nämlich der durch die Luft übertragene Schwingungsreiz, der biologisch sinnvoll nur als Warnungssignal vor Wespen gedeutet werden kann.Ein direktes, nicht erst durch Netzschwingungen vermitteltes Wahrnehmen der Luftschwingungen wird trotz bisher nicht mit Sicherheit festgestellter Schallrezeptoren wahrscheinlich gemacht.Während in den Funktionskreisen des Feindes und der Beute dem situativen Moment gegenüber den scharfumrissenen Einzelreizen somit eine sehr geringe Bedeutung zukommt, gestaltet sich die Lage für die Volketsche Auffassung günstiger im Funktionsbereich des Netzbaues. Die Bedeutung bestimmter Merkmale hängt hier wesentlich ab von der Situation im Sinne der jeweils erreichten Phase der Bauhandlung.Allerdings genügt es nicht, unter der Situation nur die Gesamtheit der äußeren Gegebenheiten zu verstehen. Wesentlich ist auch die innere Situation, in der das Tier sich befindet und auf Grund deren objektiv gleiche Bedingungen eine Umstimmung erfahren. Dies wird durch zwei Experimente gezeigt, bei denen sowohl in der Phase des Radienspinnens als auch in der Phase des Fangfädenspinnens alle gesponnenen Fäden sofort wieder mit Hilfe glühender Nadeln zerstört werden. Trotz des hierdurch hervorgerufenen Fehlens der normalen äußeren Abschlußbedingungen für die einzelnen Phasen nimmt die Bauhandlung, wenngleich in verzögerter Weise, schließlich doch ihren normalen Verlauf.     

The contribution of single and colonial cells of Phaeocystis pouchetii to spring and summer blooms in the north-eastern North Atlantic

Studies of the phytoplankton ecology in different localities in north-Norwegian fjords, the White Sea and the Barents Sea were carried out in spring and early summer to investigate the contribution of single and colonial stages of Phaeocystis pouchetii to phytoplankton abundance. Three different types of flagellated and four colonial cells were observed in all localities. P. pouchetii was rare under the ice of the Barents and White Seas, but their abundance increased rapidly during ice retreat. Single cell C dominated over colonial cell C, often by 50 times or more. The highest share of colonial cells was encountered in April in northern Norwegian fjords, in May in the Barents Sea and in May–June in the White Sea. At times the single cell dominated the total P. pouchetii biomass in Balsfjord (April 1999, 2001) with hardly any colonies present. In the White Sea colonies of P. pouchetii were less abundant than in the other regions. Cell carbon of P. pouchetii colonies appears never to be as dominating in the north-eastern North Atlantic as P. globosa blooms in coastal regions such as the southern North Sea. However, the lobal matrix of P. pouchetii colonies appears to be less solid than that of P. globosa and partly dissolution of the colony matrix during handling and storage of fixes samples induces uncertainty about the absolute numbers of P. pouchetii colonial cell counts. Despite of that, single cells of P. pouchetii seem to dominate significantly over colonial cell biomass at most sites and during some years and in some regions colonial cells seem rare. We speculate that top-down regulation of Phaeocystis spp. blooms possibly determines the ratio between single and colonial cells.     

Therapeutic vaccination against autologous cancer stem cells with mRNA-transfected dendritic cells in patients with glioblastoma

Background

The growth and recurrence of several cancers appear to be driven by a population of cancer stem cells (CSCs). Glioblastoma, the most common primary brain tumor, is invariably fatal, with a median survival of approximately 1 year. Although experimental data have suggested the importance of CSCs, few data exist regarding the potential relevance and importance of these cells in a clinical setting.

Methods

We here present the first seven patients treated with a dendritic cell (DC)-based vaccine targeting CSCs in a solid tumor. Brain tumor biopsies were dissociated into single-cell suspensions, and autologous CSCs were expanded in vitro as tumorspheres. From these, CSC-mRNA was amplified and transfected into monocyte-derived autologous DCs. The DCs were aliquoted to 9–18 vaccines containing 10⁷ cells each. These vaccines were injected intradermally at specified intervals after the patients had received a standard 6-week course of post-operative radio-chemotherapy. The study was registered with the ClinicalTrials.gov identifier NCT00846456.

Results

Autologous CSC cultures were established from ten out of eleven tumors. High-quality RNA was isolated, and mRNA was amplified in all cases. Seven patients were able to be weaned from corticosteroids to receive DC immunotherapy. An immune response induced by vaccination was identified in all seven patients. No patients developed adverse autoimmune events or other side effects. Compared to matched controls, progression-free survival was 2.9 times longer in vaccinated patients (median 694 vs. 236 days, p = 0.0018, log-rank test).

Conclusion

These findings suggest that vaccination against glioblastoma stem cells is safe, well-tolerated, and may prolong progression-free survival.     

Pollen germination in Welwitschia mirabilis Hook. f.: differences between the polyplicate pollen producing genera of the Gnetales

Pollen grains of the seed plant genera Ephedra L. and Welwitschia Hook. f. (Gnetales) are of similar size, shape, and have a polyplicate exine with alternating thicker and thinner regions. Ephedra pollen is considered inaperturate and the exine is shed during germination, leaving the male gametophyte naked. The shed exine curls up and forms a characteristic structure with transverse striations. Such upcurled exines have been found in situ in Early Cretaceous seeds with affinities to Ephedra. The purpose of this study was to document the germination of Welwitschia pollen and investigate whether they also discard their exine during this process.

The pollen grains of Welwitschia are monoaperturate with a distinct, distal sulcus. During germination, the sulcus splits open and the gametophyte expands to a spherical form that extends out of the exine. The pollen tube starts to grow one or two hours later and as in Ephedra, it is displaced towards one side. The exine is not shed but remains as a “cap” that partly covers the male gametophyte. Thus, in this respect the germination process is distinctly different from that in Ephedra and this study demonstrates that discharging the exine during pollen germination is unique to Ephedra, among the polyplicate pollen producing genera in the Gnetales.