ATP-binding cassette transporters P-glycoprotein and breast cancer related protein are reduced in capillary cerebral amyloid angiopathy

Alzheimer's disease (AD) is the most common form of dementia and marked by deposition of amyloid-β (Aβ) within the brain. Alterations of Aβ transporters at the neurovasculature may play a role in the disease process. We investigated the expression of ABC transporters P-glycoprotein (P-gp) and breast cancer related protein (BCRP) in non-neurologic controls, AD, and severe capillary cerebral amyloid angiopathy (capCAA) cases, which are characterized by deposition of Aβ within cerebral capillaries. Our data show that microvascular expression of P-gp and BCRP is strikingly decreased in capCAA-affected vessels but not in AD and control samples. Messenger RNA levels of P-gp, but not of BCRP, were downregulated in brain endothelial cells on exposure to oligomeric Aβ42, but not fibrillar Aβ42 or Aβ40. Coincubating Aβ42 together with clusterin, an amyloid-associated protein highly expressed in capCAA-affected vessels, strongly reduced levels of P-gp. In conclusion, accumulation of Aβ, in combination with clusterin, within and around cerebral capillaries, may further aggravate the disease process in AD by affecting P-gp expression. Loss of P-gp expression or activity may serve as a selective biomarker for ongoing capCAA.     

Women's Self-Reported Eating Behaviours and Their Responses to Food and Non-Food Television Advertisements

In order to stress the need for further systematic research on the relationship between the media and eating disorders, the present study investigates young women's responses to diverse consumer advertisements. Female undergraduates with varying levels of self-reported eating problems (assessed by EAT) were shown different types of food and non-food advertisements, all of which featured a slim, attractive female model. They responded after each advert in terms of (1) the emotions they experienced subjectively and (2) attributions of personal control made to the advert character. In support of the first set of hypotheses advanced, a 2 (high/low degree of eating problems) ×8 (advertisement) ANOVA showed that, compared to women with few eating problems, those with a high level of eating problems reported significantly more negative emotions after food advertisements than non-food advertisements. An ANOVA of the same format for control attributions yielded only a statistical tendency, thus providing merely tentative support for the second set of hypotheses that level of eating problems would affect control attributions to models advertising food. Theoretical and therapeutic implications are discussed of the proposition that gender-specific media messages—such as adverts which promote both a thin body ideal and food consumption—may play some role in increasing women's vulnerability to developing clinical eating disorders because they can have an aggravating effect on the substantial number of women who already have a problematic relationship with food and weight.     

A Synbiotic Formulation Comprising Bacillus subtilis DSM 32315 and L-Alanyl-L-Glutamine Improves Intestinal Butyrate Levels and Lipid Metabolism in Healthy Humans

The gut microbiota is a crucial modulator of health effects elicited by food components, with SCFA (short chain fatty acids), especially butyrate, acting as important mediators thereof. We therefore developed a nutritional synbiotic composition targeted at shifting microbiome composition and activity towards butyrate production. An intestinal screening model was applied to identify probiotic Bacillus strains plus various amino acids and peptides with suitable effects on microbial butyrate producers and levels. A pilot study was performed to test if the synbiotic formulation could improve fecal butyrate levels in healthy humans. A combination of Bacillus subtilis DSM (Number of German Collection of Microorganisms and Cell Cultures) 32315 plus L-alanyl-L-glutamine resulted in distinctly increased levels of butyrate and butyrate-producing taxa (Clostridium group XIVa, e.g., Faecalibacterium prausnitzii), both in vitro and in humans. Moreover, circulating lipid parameters (LDL-, and total cholesterol and LDL/HDL cholesterol ratio) were significantly decreased and further metabolic effects such as glucose-modulation were observed. Fasting levels of PYY (Peptide YY) and GLP-1 (Glucagon-like Peptide 1) were significantly reduced. In conclusion, our study indicates that this synbiotic composition may provide an effective and safe tool for stimulation of intestinal butyrate production with effects on e.g., lipid and glucose homeostasis. Further investigations in larger cohorts are warranted to confirm and expand these findings.     

Intracutaneous botulinum toxin A versus ablative therapy of Hailey-Hailey disease - a case report

BACKGROUND: Hailey-Hailey disease is an autosomal-dominant blistering disease affecting the intertriginous skin. Dermabrasion and ablative laser treatment are known to be curative. Sweating is a common aggravating factor. Botulinum toxin A (BTXA) has been shown to inhibit sudoriferic nerves. OBJECTIVE: To evaluate whether a treatment with BTXA induces remissions and can compete with ablative therapy. To compare dermabrasion with erbium:YAG laser therapy. METHOD: Case report with side-by-side comparison. We used intracutaneous BTXA on both sides of the submammary region. Four days later a limited area of 25 cm 2 on each side was treated with either dermabrasion or erbium:YAG laser. The follow-up was 12 months. RESULTS: Wound healing was complete within 7 days after erbium:YAG laser and two weeks after dermabrasion. Areas treated with BTXA alone also showed complete remission within two weeks. During a follow-up, no relapse occurred with either treatment. CONCLUSION: BTXA is capable of inducing remissions of Hailey-Hailey disease without abrasion for at least 12 months. Among ablative treatments, erbium: YAG laser therapy leads to a more rapid wound closure than dermabrasion, with both causing complete remissions.     

Multiple sclerosis: Demyelination and myelination inhibition of organotypic tissue cultures of the spinal cord by sera of patients with Multiple Sclerosis and other neurological diseases

Summary Sera from 44 patients with Multiple Sclerosis, of three patients with neurological syndromes compatible with Multiple Sclerosis, of 34 patients suffering from other neurological diseases and of 25 pregnant healthy young women were tested for their demyelinating activity in myelinated tissue cultures. In order to leave the investigators unprejudiced, all sera were coded and intermixed with controls of rabbit EAE serum which had a potent demyelinating capacity. Demyelination was graded (from 0–4), heat lability at 56°C (complement dependency?) was also tested with each serum. Only demyelination of a degree of 2 and more, which was abolished by heating to 56°C, was counted as positive.Six of the 44 sera from MS patients (13.6%), 19 of 37 sera from neurological patients and none of the healthy young women demyelinated. Thus, serum demyelination of tissue cultures seems to be a nonspecific indicator of chronic disease of the nervous system and is of considerable general neurological interest, but does not indicate a demyelinating disease.Myelination inhibition was not observed with any of the human sera tested for it.

---

Zusammenfassung Seren von 44 Patienten mit Multipler Sklerose (MS), 3 Patienten mit neurologischen Syndromen, bei welchen eine Multiple Sklerose nicht mit Sicherheit ausgeschlossen werden kann, von 34 Patienten mit anderen neurologischen Krankheiten und 25 gesunden schwangeren Frauen wurden auf ihre Entmarkungsaktivität in myelinisierten organotypischen Gewebskulturen geprüft. Um eine Voreingenommenheit der Untersucher möglichst zu vermeiden, wurden die Seren verschlüsselt und mit stark entmarkendem Serum eines Kaninchens mit Experimenteller Allergischer Encephalomyelitis — ebenfalls verschlüsselt — mituntersucht. Es wurden 5 Entmarkungsgrade unterschieden (0–4) und die Thermolabilität (Complement-Abhängigkeit?) bei 56°C getestet. Nur Entmarkungsgrade von 2 und mehr, die bei 56°C reduziert wurden, wurden als positiv gewertet.6 der 44 Seren von MS-Patienten (13,6%), 19 der 37 Seren von anderen neurologischen Patienten und keines von den gesunden jungen Frauen entmarkte. Somit scheint Serum-induzierte Entmarkung in Gewebskulturen ein unspezifischer Indikator chronischer neurologischer Krankheiten zu sein. Der Befund ist von erheblichem allgemeinem neurologischem Interesse, eignet sich aber nicht als Test für Entmarkungskrankheiten.Myelinationshemmung in Kulturen wurde mit keinem der getesteten Seren beobachtet.