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.

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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.

     

A proposal for the classification of dental alloys according to their resistance to corrosion.

OBJECTIVES: The purpose of this study was to establish a method to compare and classify dental alloys in relation to their resistance to corrosion. METHODS: Alloy samples and pure metal samples were prepared and tested in chemical and electrochemical corrosion according to ISO 10271. For electrochemical test, the rest potential versus time and a potentiodynamic scan were recorded. After chemical corrosion test, the ions released were analyzed by ICP (induced coupled plasma) spectroscopy. RESULTS: High gold alloys had a similar polarization curve than gold. The same effect was observed for Pd-base alloys, their curves were similar to the one of palladium. The ions released during chemical corrosion were non-precious metallic ions. Thereby Ni-Cr alloys were found to release the most ions. Au-Pt alloys showed the highest release of ions compared with other precious alloys but low compared with Ni-Cr. Electrochemical corrosion was more aggressive than chemical corrosion and every type of elements was etched, the higher the precious metal content, the higher the resistance to corrosion of the alloy. DISCUSSION: Using the recorded data, a classification system for electrochemical corrosion was developed and discussed to judge the results. Hereby were gold and zinc used as reference materials. The applied classification system defines five classes and it is proposed that alloys of class V are not acceptable. For chemical corrosion resistance, three classes were distinguished according to the quantity of metallic ions released and it is proposed that class III (100-1000 microg/cm(2)week) is not acceptable. Palladium and Pd-base alloys showed a higher electrochemical and chemical corrosion resistance than gold.     

Comprehensive rehabilitation of the child with osteogenesis imperfecta

Children with osteogenesis imperfecta (OI) that results in considerable deformity are often viewed as poor candidates for aggressive physical therapy and rehabilitation. To determine if this view is realistic, we have entered almost 50 children with OI type III and OI type IV into a comprehensive graduated rehabilitation program, based at the National Institutes of Health, but designed to be implemented by continuing involvement of community resources. Children are begun in the program early with emphasis on gain of head and trunk control and progression to sitting and walking, if possible, with the aid of a variety of phsysical supports, including internal and external bracing. Although not conducted in a randomized fashion, the program's success in bringing children into graded exercise regimes and fostering their increased involvement in school and social situations suggest that aggressive physical therpy and rehabilitation have a major place in the overall care of the infants and children with OI.     

A homozygous HFE gene splice site mutation (IVS5+1 G/A) in a hereditary hemochromatosis patient of Vietnamese origin

The vast majority of Caucasian patients presenting with hereditary hemochromatosis demonstrate a single homozygous missense mutation in the HFE gene (C282Y). The underlying genetic defects in hemochromatosis patients of non-Caucasian origin are largely unknown. A 48-year-old man of Vietnamese origin presented with insulin-dependent diabetes mellitus, tertiary adrenocortical insufficiency, and laboratory results highly indicative of hereditary hemochromatosis. Because the patient was negative for the known HFE gene mutations C282Y, H63D, and S65C HFE, the entire coding region and intron/exon boundaries of the HFE gene was investigated. Sequencing studies identified a homozygous G-to-A transition at position +1 of intron 5 (IVS5+1 G/A). This newly described mutation alters the invariant G at position +1 of the 5' splice site causing altered mRNA splicing and exon skipping with exon 4 being spliced to exon 6. Both heterozygously affected children (age 19 and 20 years) had moderately increased ferritin levels with normal serum iron concentration and transferrin saturation. The newly described mutation was not detected in a control group consisting of 220 Caucasian individuals as verified by allele-specific polymerase chain reaction. We describe for the first time a homozygous HFE splice site mutation (IVS5+1 G/A) in a non-Caucasian patient with hereditary hemochromatosis. Although the absence of this novel HFE gene mutation in Caucasian subjects suggests that the mutation is exclusive to this family, mutation screening in populations of different ethnic background is recommended to precisely define its contribution to hereditary hemochromatosis in non-Caucasian patients.     

CTLA-4 up-regulation of lymphocyte function-associated antigen 1 adhesion and clustering as an alternate basis for coreceptor function

Although cytotoxic T lymphocyte antigen-4 (CTLA-4) negatively regulates T cell activation, the full range of functions mediated by this coreceptor has yet to be established. In this study, we report the surprising finding that CTLA-4 engagement by soluble antibody or CD80 potently up-regulates lymphocyte function-associated antigen 1 (LFA-1) adhesion to intercellular adhesion molecule-1 (ICAM-1) and receptor clustering concurrent with IL-2 inhibition. This effect was also observed with CTLA-4 ligation and not with other coreceptors. T cell antigen receptor (TcR)-induced lymphocyte function-associated antigen 1 function was also dependent on CTLA-4 expression as observed with reduced adhesion/clustering on CTLA-4(-/-) primary T cells. CTLA-4 up-regulated adhesion was mediated by regulator for cell adhesion and polarization type 1 (Rap-1) as shown by anti-CTLA-4-induced Rap-1 activation as well as Rap-1-N17 blockade and Rap-1-V12 mimicry of adhesion/clustering. Our findings identify a potent role for CTLA-4 in directing integrin adhesion and provide an alternate mechanism to account for aspects of CTLA-4 function in T cell immunity.