Veränderungen in der Menge des Prostaglandins F2 alpha bei Schnittwunden der Haut mit verschiedener Zeitdauer ihres Bestehens

Zusammenfassung Beschrieben wird eine radioimmunologische Methode zum Nachweis der Prostaglandin F_{2 alpha}-Menge in Schnittwunden der Haut von Meerschweinchen. Bei zu Lebzeiten zugefügten Hautverletzungen finden sich schnell ansteigende Prostaglandin F_{2 alpha}-Mengen, die 1 Stunde nach der Verletzung bis 71 ng/g erreichen. Nach der Tötung der Tiere sinken die konstatierten Mengen in zu Lebzeiten gesetzten Wunden allmählich ab und erreichen in der 6. Std nach dem Tode 17 ng/g. In postmortal zugefügten Verletzungen, die spätestens bis zur 8. Std nach dem Tode gesetzt wurden, findet man eine Menge des untersuchten Prostaglandins in Höhe von etwa 14–18 ng/g. In späteren postmortalen Wunden beträgt die Menge dieses Prostaglandins etwa 9–10 ng/g. Die Unterschiede erlauben es, die Untersuchung des Prostaglandins F_{2 alpha} zum Beweis dafür anzuwenden, ob eine Hautwunde zu Lebzeiten zugefügt wurde und wieviel Zeit danach vergangen ist.     

Fossilized Venom: The Unusually Conserved Venom Profiles of Heloderma Species (Beaded Lizards and Gila Monsters)

Research into snake venoms has revealed extensive variation at all taxonomic levels. Lizard venoms, however, have received scant research attention in general, and no studies of intraclade variation in lizard venom composition have been attempted to date. Despite their iconic status and proven usefulness in drug design and discovery, highly venomous helodermatid lizards (gila monsters and beaded lizards) have remained neglected by toxinological research. Proteomic comparisons of venoms of three helodermatid lizards in this study has unravelled an unusual similarity in venom-composition, despite the long evolutionary time (~30 million years) separating H. suspectum from the other two species included in this study (H. exasperatum and H. horridum). Moreover, several genes encoding the major helodermatid toxins appeared to be extremely well-conserved under the influence of negative selection (but with these results regarded as preliminary due to the scarcity of available sequences). While the feeding ecologies of all species of helodermatid lizard are broadly similar, there are significant morphological differences between species, which impact upon relative niche occupation.     

Magnetic and Tunable Sound Absorption Properties of an In-Situ Prepared Magnetorheological Foam

Conventional polyurethane foam has non-tunable sound absorption properties. Here, a magneto-induced foam, called magnetorheological (MR) foam, was fabricated with the feature of being able to tune sound absorption properties, primarily from the middle- to higher-frequency ranges. Three different samples of MR foams were fabricated in situ by varying the concentration of Carbonyl Iron Particles (CIPs) (0, 35, and 75 wt.%). The magnetization properties and tunable sound absorption characteristics were evaluated. From the magnetic saturation properties, the results showed very narrow and small coercivity of hysteresis loops relative to the soft magnetic properties of the CIPs. MR foam with 75 wt.% CIPs showed a higher magnetic saturation at 91.350 emu/g compared to MR foam with 35 wt.% CIPs at 63.896 emu/g. For tunable sound absorption testing, the effect of ‘shifting’ to higher frequency was also observed when the magnetic field was applied, which was ~10 Hz for MR foam with 35 wt.% CIPs and ~130 Hz for MR foam with 75 wt.% CIPs. As the latest evolution of semi-active noise control materials, the results from this study are valuable guidance for the advancement of MR-based devices.     

Disturbed function of the blood–cerebrospinal fluid barrier aggravates neuro-inflammation

Multiple sclerosis (MS) is a chronic neuro-inflammatory disorder, which is marked by the invasion of the central nervous system by monocyte-derived macrophages and autoreactive T cells across the brain vasculature. Data from experimental animal models recently implied that the passage of leukocytes across the brain vasculature is preceded by their traversal across the blood–cerebrospinal fluid barrier (BCSFB) of the choroid plexus. The correlation between the presence of leukocytes in the CSF of patients suffering from MS and the number of inflammatory lesions as detected by magnetic resonance imaging suggests that inflammation at the choroid plexus contributes to the disease, although in a yet unknown fashion. We here provide first insights into the involvement of the choroid plexus in the onset and severity of the disease and in particular address the role of the tight junction protein claudin-3 (CLDN3) in this process. Detailed analysis of human post-mortem brain tissue revealed a selective loss of CLDN3 at the choroid plexus in MS patients compared to control tissues. Importantly, mice that lack CLDN3 have an impaired BCSFB and experience a more rapid onset and exacerbated clinical signs of experimental autoimmune encephalomyelitis, which coincides with enhanced levels of infiltrated leukocytes in their CSF. Together, this study highlights a profound role for the choroid plexus in the pathogenesis of multiple sclerosis, and implies that CLDN3 may be regarded as a crucial and novel determinant of BCSFB integrity.     

Deletion of claudin-10 (Cldn10) in the thick ascending limb impairs paracellular sodium permeability and leads to hypermagnesemia and nephrocalcinosis

In the kidney, tight junction proteins contribute to segment specific selectivity and permeability of paracellular ion transport. In the thick ascending limb (TAL) of Henle's loop, chloride is reabsorbed transcellularly, whereas sodium reabsorption takes transcellular and paracellular routes. TAL salt transport maintains the concentrating ability of the kidney and generates a transepithelial voltage that drives the reabsorption of calcium and magnesium. Thus, functionality of TAL ion transport depends strongly on the properties of the paracellular pathway. To elucidate the role of the tight junction protein claudin-10 in TAL function, we generated mice with a deletion of Cldn10 in this segment. We show that claudin-10 determines paracellular sodium permeability, and that its loss leads to hypermagnesemia and nephrocalcinosis. In isolated perfused TAL tubules of claudin-10-deficient mice, paracellular permeability of sodium is decreased, and the relative permeability of calcium and magnesium is increased. Moreover, furosemide-inhibitable transepithelial voltage is increased, leading to a shift from paracellular sodium transport to paracellular hyperabsorption of calcium and magnesium. These data identify claudin-10 as a key factor in control of cation selectivity and transport in the TAL, and deficiency in this pathway as a cause of nephrocalcinosis.     

Radial scar lesions of the breast diagnosed by needle core biopsy: analysis of cases containing occult malignancy

AIM: To identify and review cases of false negative needle core biopsy (NCB) in the preoperative investigation of radial scar/complex sclerosing lesion (RS/CSL) lesions - that is, benign NCB from RS/CSL which contained malignancy on excision. METHODS AND RESULTS: A total of 11 false negative NCB in RS/CSL lesions from 281 (3.9%) were identified (6 cases: B1, 2 cases: B2 and 3 cases: B3). In 6 of 11 cases a radial scar or stromal sclerosis was seen in NCB. Localisation biopsy showed duct carcinoma in situ in six cases, duct carcinoma in situ with invasive carcinoma in three and invasive carcinoma in two. In all 11 cases, needle tracks were identified as missing the malignant epithelium by a mean of 5 mm (median:4 mm; range:1-20 mm). In 9 of 11 cases, the malignancy was missed by <6 mm. CONCLUSIONS: Despite evidence of accurate targeting of lesions, the use of NCB instead of fine needle aspiration cytology has not eliminated the problem of false negative biopsy in RS/CSL, and excision is recommended.