The liver-resident immune cell repertoire - A boon or a bane during machine perfusion?

The liver has been proposed as an important "immune organ" of the body, as it is critically involved in a variety of specific and unique immune tasks. It contains a huge resident immune cell repertoire, which determines the balance between tolerance and inflammation in the hepatic microenvironment. Liver-resident immune cells, populating the sinusoids and the space of Disse, include professional antigen-presenting cells, myeloid cells, as well as innate and adaptive lymphoid cell populations. Machine perfusion (MP) has emerged as an innovative technology to preserve organs ex vivo while testing for organ quality and function prior to transplantation. As for the liver, hypothermic and normothermic MP techniques have successfully been implemented in clinically routine, especially for the use of marginal donor livers. Although there is evidence that ischemia reperfusion injury-associated inflammation is reduced in machine-perfused livers, little is known whether MP impacts the quantity, activation state and function of the hepatic immune-cell repertoire, and how this affects the inflammatory milieu during MP. At this point, it remains even speculative if liver-resident immune cells primarily exert a pro-inflammatory and hence destructive effect on machine-perfused organs, or in part may be essential to induce liver regeneration and counteract liver damage. This review discusses the role of hepatic immune cell subtypes during inflammatory conditions and ischemia reperfusion injury in the context of liver transplantation. We further highlight the possible impact of MP on the modification of the immune cell repertoire and its potential for future applications and immune modulation of the liver.

Role of BDNF and neurotrophic receptors in human inner ear development.

The expression patterns of the neurotrophin, brain-derived neurotrophic factor, BDNF, and the neurotrophic receptors-p75NTR and Trk receptors-in the developing human fetal inner ear between the gestational weeks (GW) 9 to 12 are examined via in situ hybridization and immunohistochemistry. BDNF mRNA expression was highest in the cochlea at GW 9 but declined in the course of development. In contrast to embryonic murine specimens, a decline in BDNF expression from the apical to the basal turn of the cochlea could not be observed. p75NTR immunostaining was most prominent in the nerve fibers that penetrate into the sensory epithelia of the cochlea, the urticule and the saccule as gestational age progresses. TrkB and TrkC expression intensified towards GW 12, at which point the BDNF mRNA localization was at its lowest. TrkA expression was limited to fiber subpopulations of the facial nerve at GW 10. In the adult human inner ear, we observed BDNF mRNA expression in the apical poles of the cochlear hair cells and supporting cells, while in the adult human utricle, the expression was localized in the vestibular hair cells. We demonstrate the highly specific staining patterns of BDNF mRNA and its putative receptors over a developmental period in which multiple hearing disorders are manifested. Our findings suggest that BDNF and neurotrophin receptors are important players during early human inner ear development. In particular, they seem to be important for the survival of the afferent sensory neurons.

The pre- and post-somatic segments of the human type I spiral ganglion neurons--structural and functional considerations related to cochlear implantation.

Human auditory nerve afferents consist of two separate systems; one is represented by the large type I cells innervating the inner hair cells and the other one by the small type II cells innervating the outer hair cells. Type I spiral ganglion neurons (SGNs) constitute 96% of the afferent nerve population and, in contrast to other mammals, their soma and pre- and post-somatic segments are unmyelinated. Type II nerve soma and fibers are unmyelinated. Histopathology and clinical experience imply that human SGNs can persist electrically excitable without dendrites, thus lacking connection to the organ of Corti. The biological background to this phenomenon remains elusive. We analyzed the pre- and post-somatic segments of the type I human SGNs using immunohistochemistry and transmission electron microscopy (TEM) in normal and pathological conditions. These segments were found surrounded by non-myelinated Schwann cells (NMSCs) showing strong intracellular expression of laminin-ß2/collagen IV. These cells also bordered the perikaryal entry zone and disclosed surface rugosities outlined by a folded basement membrane (BM) expressing laminin-ß2 and collagen IV. It is presumed that human large SGNs are demarcated by three cell categories: (a) myelinated Schwann cells, (b) NMSCs and (c) satellite glial cells (SGCs). Their BMs express laminin-ß2/collagen IV and reaches the BM of the sensory epithelium at the habenula perforata. We speculate that the NMSCs protect SGNs from further degeneration following dendrite loss. It may give further explanation why SGNs can persist as electrically excitable monopolar cells even after long-time deafness, a blessing for the deaf treated with cochlear implantation.

The feline iodine requirement is lower than the 2006 NRC recommended allowance.

The purpose of this study was to determine the iodine (I) requirement in adult cats. Forty-two healthy euthyroid cats (1.6-13.6 years old) were utilized in a randomized complete block design. Cats were fed a dry basal diet (0.23 mg/kg I) for a minimum of 1 month (pre-test) then switched to a different basal diet supplemented with seven levels of KI for 1 year (experimental period). Analysed I concentrations were 0.17, 0.23, 0.47, 1.1, 3.1, 6.9 and 8.8 mg I/kg diet [dry matter (DM) basis] and used to construct a response curve. Response variables included I concentrations in serum, urine and faeces, urinary I:creatinine ratio, I balance, technetium(99m) pertechnetate (Tc(99m)) thyroid:salivary ratio, complete blood count and serum chemistries as well as serum thyroid hormone profiles. No significant changes in food intake, weight gain or clinical signs were noted. Serum I, daily urinary I, daily faecal I and urinary I:creatinine ratio were linear functions of iodine intake. An estimate of the I requirement (i.e. breakpoint) was determined from regression of Tc(99m) thyroid:salivary ratio (scintigraphy) on I intake at 12 months [0.46 mg I/kg diet (DM basis) as well as 9 months I balance (0.44 mg I/kg diet (DM)]. The I requirement estimate determined in our study at 12 months for adult cats (0.46 mg I/kg) was higher than current Association of American Feed Control Officials (AAFCO) recommendations (e.g. 0.35 mg I/kg), but was lower than the 2006 National Research Council (NRC) I recommended allowance (e.g. 1.4 mg I/kg).

Use of tylvalosin-medicated feed to control porcine proliferative enteropathy.

The effect of an oral treatment with the tartrate salt of tylvalosin on the development of proliferative enteropathy in 60 experimentally challenged pigs was studied. Thirty of the pigs were fed a diet medicated with 50 ppm tylvalosin and 30 were fed the unmedicated diet. The treated animals started to receive the medicated feed the day before they were inoculated, and continued to receive it for 14 days. The pigs' bodyweight, feed consumption and clinical signs were evaluated, and they were examined postmortem 20 days after inoculation, and samples of ileum were collected for immunohistochemistry (IHC) for Lawsonia intracellularis. Clinical signs of the disease were more evident in the untreated group than in the treated group. The average daily weight gain, average daily feed consumption and feed conversion efficiency were better in the treated group. The combined length of intestine with lesions was 2847 cm in the untreated group and 183 cm in the treated group. The tylvalosin treatment significantly reduced the level of L intracellularis infection; almost half of the treated pigs were IHC-negative compared with 3.3 per cent of the untreated pigs.

Cartilage canals in the chicken embryo: ultrastructure and function.

In this study the detailed morphology and the function of cartilage canals in the chicken femur are investigated. Several embryonic stages (e 13.5, 16, 19, and 20) are examined by means of light microscopy, electron microscopy (TEM), and immunohistochemistry (VEGF, type I and II collagen). Our results show that cartilage canals originate from the perichondrium and form a complex pattern. Two types of canals are distinguishable: shell canals and communicating canals. Shell canals are in the reserve zone and are arranged in successive layers. Communicating canals spring from the shell canals and pass down into the proliferative zone and into the hypertrophic zone. These canals are conical shaped and are orientated nearly in parallel to the long axis of the femur. Cartilage canals comprise venules, arterioles, capillaries (mature and immature), and undifferentiated mesenchymal cells. No canal wall in the sense of an epithelium is elaborated. VEGF is detected in both types of canals and macrophages are found at the end of the cartilage canals. We conclude that the growth factor stimulates angiogenesis and that the latter cells erode the matrix ahead of the canals and thus enable the advancement of the vessels. The results clearly show that the canal matrix differs from the remaining cartilage matrix. The canal matrix contains type I collagen, few type II collagen fibrils and proteoglycans are lacking. In contrast, in the cartilage matrix type II collagen and proteoglycans are abundant but no type I collagen is found. Communicating canals are surrounded by a distinct layer of type I collagen indicating that osteoid is formed around these canals. Hypertrophic chondrocytes label for type I collagen and it seemed possible that chondrocytes adjacent to the communicating canals differentiate into bone-forming cells. Our results provide evidence that cartilage canals are involved in nourishment of the cartilage as well as in the ossification process.

Azaarenes in recent marine sediments.

Chemical fractionation and mass spectral probe distillation reveal the presence in recent marine sediments of a complex assemblage of nitrogen-containing aromatic compounds. These azaarenes range from three- to eight-membered rings, with homologs containing up to eight alkyl carbons. In their composition, and presumably in their origin in natural fires, they resemble the aromatic hydrocarbons found in the same sediments. The analytical, geochemical, and environmental implications of these findings are discussed.

Polycyclic aromatic hydrocarbons in soils and recent sediments.

Soils and recent marine sediments contain a complex polycyclic aromatic hydrocarbon assemblage. There is a high degree of similarity in the molecular weight distribution of the many series of alkyl homologs of these aromatic hydrocarbons, and this distribution varies little over a wide range of depositional environments. The evidence suggests that these hydrocarbons are formed in natural fires, are dispersed and mixed by air transport, and are eventually deposited into surface sediments. The analytical, geochemical, and environmental implications of these findings are discussed.

Oil pollution: persistence and degradation of spilled fuel oil.

In September 1969, approximately 600 metric tons of number 2 fueloil were spilled in Buzzards Bay, Massachusetts. Two years later, fuel oil hydrocarbons still persisted in the marsh and in offshore sediments. Hydrocarbon degradation is slow, especially below the immediate sediment surface and appears to proceed principally through microbial utilization of alkanes and through partial dissolution of the lower-boiling aromatic hydrocarbons. The boiling range of the spilled oil and the relative abundances of homologous hydrocarbons (for example, phytane and pristane) have been well preserved. The findings are in agreement with the known geochemical stability of hydrocarbons. Fuel oil is an appreciable fraction of whole crude oil. This fact suggests that oil products and crude oils have a considerable environmental persistence.

Fatty acids in the lipids of marine and terrestrial nitrifying bacteria.

Fatty acids in the lipids of 19 marine and terrestrial nitrifying bacteria have been analyzed. Ammonia-oxidizing bacteria have a very simple acid composition; palmitic and palmitoleic acid account for 96 to 100% of the total acids. The fatty acids of nitrite-oxidizing bacteria cover a wider range, from C(14) to C(19), but from two to four acids still account for more than 80% of the total acids. Branched iso- and anteiso-acids are present in traces only in 2 of the 19 bacteria. The chemical and morphological similarity between blue-green algae and these bacteria is discussed.

On the origin of pristane in marine organisms.

Phytol-U-(14)C was adsorbed on algae and ingested in this form by zooplanktonic copepods (two species of Calanus). The lipids of these animals were analyzed after 48 hr and found to contain radioactive pristane and radioactive phytanic acid. The conversion of phytol to pristane by the copepods is interpreted as a likely biological source of pristane in nature.

Isoprenoid acids in recent sediments.

Phytanic acid, pristanic acid, and 4,8,12-trimethyltridecanoic acid have been isolated from three recent marine sediments. The ratio of palmitic to pristanic acid is similar to that encountered in typical marine lipids. This suggests a biochemical origin of these sedimentary acids; phytol is their presumed biochemical precursor. Other isoprenoid acids between C(11) and C(22) which are common in ancient sediments have not been found. They are probably geochemical products formed slowly and at a greater depth.

Hydrocarbons in digestive tract and liver of a basking shark.

The hydrocarbons of zooplankton pass through the digestive tract of the basking shark without fractionation or structural modification. They are resorbed in the spiral valve and deposited in the liver. In contrast to unsaturated fatty acids, the olefinic hydrocarbons are not decreased in concentration. The hydrocarbon assemblage in the digestive tract and in the liver is indicative of the food sources and feeding grounds of the shark. Squalene, abundant in shark liver, occurs only in traces in zooplankton; phytane, if present at all, constitutes less than 0.005 percent of the hydrocarbons of zooplankton and of shark liver.