Cell-mediated immunosenescence in birds

The phytohaemagglutinin (PHA) skin test response, used to assess cell-mediated immunity, is known to vary with many social and energetic factors, but the effects of age have received little attention. We found that the PHA response of immature birds was lower than those of the youngest breeding adults and were decreased in adults. Whenever possible, age should be included as a covariate when the PHA skin test is used to assess immunocompetence in ecological immunology. The rate of decline in PHA response differed between species and was inversely correlated with survival. The decrease in the PHA response averaged 57% over an average 80% of the maximum life span, but the absolute rate varied with species lifespan such that the short-lived species showed a greater loss per year than the long-lived species. This link between declining immune function and survival may reflect differences in resource partitioning between species, and suggests that selection may act on investment in immune function to influence maximum life span.     

A low molecular weight copper chelator crosses the blood-brain barrier and attenuates experimental autoimmune encephalomyelitis

Increasing evidence suggests that enhanced production of reactive oxygen species (ROS) activates the MAP kinases, c-Jun N-terminal protein kinase (JNK) and mitogen-activated protein kinase MAPK (p38). These phosphorylated intermediates at the stress-activated pathway induce expression of matrix metalloproteinases (MMPs), leading to inflammatory responses and pathological damages involved in the etiology of multiple sclerosis (MS). Here we report that N-acetylcysteine amide (AD4) crosses the blood-brain barrier (BBB), chelates Cu(2+), which catalyzes free radical formation, and prevents ROS-induced activation of JNK, p38 and MMP-9. In the myelin oligodendrocyte glycoprotein (MOG)-induced experimental autoimmune encephalomyelitis (EAE), a mouse model of MS, oral administration of AD4 drastically reduced the clinical signs, inflammation, MMP-9 activity, and protected axons from demylination damages. In agreement with the in vitro studies, we propose that ROS scavenging by AD4 in MOG-treated animals prevented MMP's induction and subsequent damages through inhibition of MAPK pathway. The low toxicity of AD4 coupled with BBB penetration makes this compound an excellent potential candidate for the therapy of MS and other neurodegenerative disorders.     

Behavioural and electrophysiological responses of the malaria mosquito Anopheles gambiae Giles sensu stricto (Diptera: Culicidae) to human skin emanations

Behavioural and electrophysiological responses of Anopheles gambiae Giles sensu stricto (Diptera: Culicidae) to human skin emanations collected on glass beads were studied using a dual-port olfactometer and electroantannography. Glass beads to which skin emanations from human hands had been transferred elicited a level of attraction similar to a human hand. The attractiveness of these handled glass beads faded away 4 h after transfer onto the beads. Storage at -20 degrees C for up to 8 weeks showed a decreased but still attractive effect of the beads. In a choice test between one individual and four others, the emanations from the reference individual were significantly more attractive in three out of four cases. The headspace of handled glass beads elicited a dose-dependent EAG response. The substances causing EAG activity could be removed partially by dichloromethane, ethanol and pentane-ether. Glass beads provide a suitable neutral substrate for the transfer of human odour to enable chemical analysis of the human skin emanations for identification of kairomones of anthropophilic mosquitoes.     

Location and phenotype of human adult keratinocyte stem cells of the skin

The location and identity of interfollicular epidermal stem cells of adult human skin remain undefined. Based on our previous work in both adult murine and neonatal human foreskin, we demonstrate that cell surface levels of the alpha6 integrin and the transferrin receptor (CD71) are valid markers for resolving a putative stem cell, transit amplifying and differentiating compartment in adult human skin by flow cytometry. Specifically, epidermal cells expressing high levels of alpha6 integrin and low levels of the transferrin receptor CD71 (phenotype alpha6 (bri)CD71(dim)) exhibit several stem cell characteristics, comprising a minor population (2%-5%) of the K14(bri) fraction, enriched for quiescent and small blast-like cells with high clonogenic capacity, lacking the differentiation marker K10. Conversely, the majority of K14(bri) K10(neg) epidermal cells express high levels of CD71 (phenotype alpha6 (bri)CD71(bri)), and represent the actively cycling fraction of keratinocytes displaying greater cell size due to an increase in cytoplasmic area, consistent with their being transient amplifying cells. The alpha6 (bri)CD71(bri) population exhibited intermediate clonogenic capacity. A third population of K14(dim) but K10 positive epidermal cells could be identified by their low levels of alpha6 integrin expression (i.e. alpha6 (dim) cells), representing the differentiation compartment; predictably, this subpopulation exhibited poor clonogenic efficiency. Flow cytometric analysis for the hair follicle bulge region (stem cell) marker K15 revealed preferential expression of this keratin in alpha6 (bri) cells (i.e., both stem and transient amplifying fractions), but not the alpha6 (dim) population. Given that K15 positive cells could only be detected in the deep rete ridges of adult skin in situ, we conclude that stem and transient amplifying cells reside in this location, while differentiating (K15 negative) cells are found in the shallow rete ridges.     

Effect of mercuric chloride on electrical parameters and anion fluxes in the toad skin

The amphibian skin, widely used for studying the transepithelial passage of electrolytes, exhibits anion pathways relatively specific for Cl(-). We studied the effect of HgCl(2), 1.0 x 10(-4) M on its electrical parameters and unidirectional anion fluxes. In the presence of Cl(-), the transepithelial conductance (G) of the isolated skin of the Bufo arenarum toad increased considerably following exposure to HgCl(2), whereas short-circuit current (SCC)--reflecting transepithelial Na(+) transport-underwent only slight stimulation. Following the blockade of Na(+) intake by amiloride, 1.0 x 10(-4) M, the removal of Cl(-) from the solution bathing the epidermal border of the skin brought about a decrease in G, and gave rise to a gradient-induced SCC (SCCg) consistent with transepithelial passage of Cl(-) along its gradient. Addition of mercaptoethanol, 5.0 x 10(-3) M to the bath containing Hg(2+) fully reversed these effects. The increase in G was accompanied by an increase in the unidirectional (epidermal to dermal) fluxes of (36)Cl(-) and (131)I(-), and a decrease in the passage of (99m)TcO(4)(-). These results show the effects of HgCl(2) to be similar to those of theophylline, although exhibiting a different selectivity. Our data suggest that anion passage following exposure to HgCl(2) is, like that stimulated by theophylline, predominantly if not exclusively transcellular, and does not involve a significant opening of the tight junctions.     

Helicobacter pylori and autoimmune pancreatitis: role of carbonic anhydrase via molecular mimicry?

Autoimmune pancreatitis is a recently defined nosological entity, which accounts for 4.6-6% of all forms of chronic pancreatitis and is often associated with other autoimmune diseases, particularly Sjogren's syndrome. Possession of the HLA DRB1*0405-DQB1*0401 genotype confers a risk for the development of autoimmune pancreatitis. Autoantibodies against carbonic anhydrase II and lactoferrin are frequently present in affected subjects and are suspected to have a pathogenic role. A link between gastric infection by Helicobacter pylori and autoimmune pancreatitis has been hypothesized. We used in silico protein analysis and search for HLA binding motifs to verify this hypothesis. We found a significant homology between human carbonic anhydrase II and alpha-carbonic anhydrase of Helicobacter pylori, an enzyme which is fundamental for the survival and proliferation of the bacterium in the gastric environment. Moreover, the homologous segments contain the binding motif of the HLA molecule DRB1*0405. Our data strengthen the hypothesis that gastric Helicobacter pylori infection can trigger autoimmune pancreatitis in genetically predisposed subjects.     

Zu den Nervenendigungen (Merkeische Endigungen) in der haarlosen Nasenhaut der Katze

Zusammenfassung Die Nervenendigungen in der Epidermis der haarlosen Haut der Katzennase wurden licht- und elektronenmikroskopisch untersucht. Im Stratum germinativum werden Merkeische Endigungen gefunden. Sie bestehen aus spezialisierten Zellen und je einer anliegenden verdickten Nervenfaser. Diese Rezeptoren werden in zwei Formen beobachtet. Einzelne Zell-Neurit-Komplexe liegen in der Basalschicht der Epidermis über den bindegewebigen Papillen und Gruppen solcher Komplexe im Stratum germinativum der Epidermalleisten (Epithelialzapfen). Die spezialisierten Zellen sind mit den umliegenden Epidermiszellen durch Desmosomen verbunden.Freie Nervenendigungen konnten in der Epidermis der haarlosen Nasenhaut nicht beobachtet werden.

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Nerve endings (Merkel's corpuscles) in hairless skin of the nose of cat

Summary The nerve endings in the epidermis of the hairless skin of the nose of the cat have been studied by means of light and electron microscopy. In the stratum germinativum there are Merkel's corpuscles. They consist of specialized cells with a thickened nerve fibre adjacent to each one of them. These receptors have been observed in two forms. Single cell-neurit-complexes are lying in the basal layer of the epidermis above the connective tissue papillae, and groups of these complexes are situated in the interpapillary pegs of the epidermis. The specialized cells are connected by desmosomes with the neighbouring cells of the epidermis. There are no free nerve endings in the hairless skin of the nose.

     

使用富血小板血浆对下肢慢性创面缺损的临床研究分析

目的:研究和探讨使用富血小板血浆(platelet-rich plasma, PRP)在人体下肢慢性创面缺损中的治疗作用,并试图寻找更佳的治疗皮肤慢性缺损的治疗方式。方法:对2016.03-2017.03一年以来在我科治疗,明确诊断为慢性创面缺损的,经纳入和排除标准筛选的共计16名患者进行分析。将其分为实验组(8人)与对照组(8人)。实验组通过对静脉血(肘部)进行抽取离心来制备富血小板血浆并加以覆盖。对照组则使用重组人表皮生长因子进行替代。两组患者均以7天为一疗程,进行换药和更换辅料。比较两组患者的创面愈合情况并比较其血液指标。结果:实验组患者在治疗后1周时观察创面,发现创面无明显渗出及感染征象,其面积缩小约1/4。对照组在1周后进行观察,发现1例有感染可能,给予再次清创并使用抗生素后辅料包扎。其余患者创面肉芽生长可,面积缩小约1/6。在治疗2周后再次进行观察,发现实验组患者创面面积缩小约2/3。而对照组患者面积缩小约1/4。在治疗后3周时,实验组所有患者创面已基本愈合85%以上。在延迟治疗1-2周后该组患者全部愈合。对照组患者在治疗3周后有两例患者愈合面积在50%以上。给予继续使用该治疗方法。剩余6例患者接受外科治疗(VSD+植皮/皮瓣)。实验组患者在各治疗观察点皮肤愈合情况较对照组均有显著改善(P0.05)。两组所有患者均未出现严重并发症。结论:对于下肢慢性创面,使用富血小板血浆进行治疗,能够有效的促进创面愈合,减少手术及外科治疗的风险,降低治疗费用,且相对安全,具有非常重要的临床推广价值。     

Gut Microbes Egested during Bites of Infected Sand Flies Augment Severity of Leishmaniasis via Inflammasome-Derived IL-1β

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