Time-dependent changes in neurokinin(3) receptors and tachykinins during adjuvant-induced peripheral inflammation in the rat

Although considerable evidence exists that spinal neurokinin(1) receptors are involved in central sensitization of nociception, recent evidence from knockout studies indicates that other neurokinin receptors in the spinal cord may mediate a portion of the hyperalgesia caused by substance P and neurokinin A. The present study determined whether the second most abundant class of neurokinin receptors, neurokinin(3) receptors, are regulated during persistent peripheral inflammation. Inflammation in the hind paw of the rat was induced by intraplantar injection of complete Freund's adjuvant. Receptor autoradiography revealed specific binding of [125I]-MePhe(7)-NKB, a selective ligand for neurokinin(3) receptors, in the superficial dorsal horn of the spinal cord. Specific binding of [125I]-MePhe(7)-NKB in the medial dorsal horn was reduced bilaterally two days after unilateral injection of complete Freund's adjuvant. Binding returned to basal levels four days after injection of complete Freund's adjuvant. Neurokinin(3) receptor messenger RNA levels doubled in the dorsal spinal cord at 12h and remained elevated for at least four days. The change in neurokinin(3) receptor binding and messenger RNA during adjuvant-induced inflammation may be a consequence of activation of the receptor. Spinal levels of potential endogenous ligands for spinal neurokinin(3) receptors were measured by radioimmunohistochemistry. Immunoreactive substance P but not neurokinin B peptide 2, a marker for neurokinin B, was reduced bilaterally during adjuvant-induced inflammation.Collectively, these data indicate that spinal neurokinin(3) receptors may play a role in spinal neurotransmission of injured rats and require consideration of other tachykinins as physiologically relevant ligands to spinal neurokinin(3) receptors.     

The interplay between host haemostatic systems and Leptospira spp. infections

Abstract

Hemostasis is a defence mechanism that protects the integrity of the vascular system and is comprised of the coagulation cascade, fibrinolysis, platelet aggregation, and vascular endothelium. Besides the primary function in preserving the vascular integrity, the haemostatic system cooperates with immune and inflammatory processes to eliminate invading pathogens during microbial infections. Under pathological manifestations, hemostasis must therefore interact in a coordinated manner with inflammatory responses and immune reactions. Several pathogens can modulate these host-derived countermeasures by specifically targeting certain haemostatic components for their own benefit. Thus, the ability to modulate host defence systems has to be considered as an essential bacterial virulence mechanism. Complications that bacterial pathogens can induce are therefore often the consequence of evoked host responses. A comprehensive understanding of the molecular mechanisms triggered in infectious processes may help to develop prophylactic methods and novel therapies for the patients suffering from a particular infectious disease. This review aims to provide a critical updated compiling of recent studies on how the pathogenic Leptospira can interact with and manipulate the host haemostatic systems and the consequences for leptospirosis pathogenesis.     

Effects of mild leg exercise in a seated position on haemostatic parameters under normobaric hypoxic conditions.

This study tested the hypothesis that in humans mild leg exercise affects haemostasis in normobaric hypoxia and thus avoids the development of a deep venous thrombosis (DVT). Eight young men breathed in a 15.4% oxygen in nitrogen gas mixture for 2 hrs while seated at rest (R) or seated and performing a 3-min mild leg exercise program (Ex) at 15-min intervals to assess the impact of mild leg exercise on haemostatic parameters related to the risk of developing DVT, as has been discussed for hypobaric hypoxic conditions during commercial airline travel. Capillary blood gases were analysed every 30 min. Heart rate was monitored continuously. Haemostatic parameters were analysed from venous blood at the beginning, after 1 and 2 hrs, and after a 30-min resting period in normoxic conditions. Plasminogen-activator-inhibitor-1 diminished in both tests in hypoxia, but not after the resting period. Antithrombin-III decreased in R in the hypoxic period. Platelet count, international normalized ratio, partial thromboplastin time remained unchanged, as did highly sensitive parameters like tissue-plasminogen-activator, alpha2-antiplasmin, d-dimers, thrombin-antithrombin-III-complexes, and prothrombin-fragments 1 and 2. The haematocrit decreased significantly in R. The mild leg execise prevented the decrease of antithrombin-III and caused an increase in haematocrit after an initial drop in the first hour. The present study revealed that normobaric hypoxia did not have clinically relevant effects on haemostasis in humans. Mild leg exercise carried out under those conditions did not lead, via alterations in haemostasis, to a reduced risk of DVT.     

Segmental differences in electrical properties and Na-transport of rabbit caecum,proximal and distal colon in vitro

Electrical potential difference, short circuit current, tissue conductance, and unidirectional Na-fluxes were measured in four segments of the rabbit large intestine in vitro. Compared to the relatively tight, low conductance distal colon, caecum and proximal parts of the colon are leaky epithelia with high conductances. Net Na-absorption was highest in caecum, and then decreased gradually towards the distal colon, whereas potential and short circuit current where high in the caecum and proximal colon, low in the middle part of the colon, and high again in the distal colon. Unidirectional Na-fluxes of all four segments were different.The discrepancy between the short circuit current and net Na-absorption in the two segments of the proximal colon indicates electrogenic transport of other ions. 0.1 mM ouabain virtually abolished short circuit current and Na-absorption in all segments, whereas 0.1 mM amiloride was not effective in the caecum and the proximal colonic parts. The present study focuses on the comparative aspects of Na-transport. It demonstrates the marked segmental heterogeneity of the basic electrical properties and suggests four different segmental organizations of large intestinal electrolyte transport.     

The pigment architecture of the human frontal lobe

Summary The precentral, subcentral, and frontal region of the human frontal lobe were examined by means of stereomicroscopical analysis using 800 m thick pigment preparations.The precentral region can be divided into markedly externoteniate ganglionic core fields and weakly externoteniate paraganglionic belt areas. The core fields are in addition characterized by a conspicuous population of pigment-laden Betz-pyramids in layer ^pVb. A typical pattern of pigmentation permits their clear distinction from other pyramidal cells of the fifth layer. When passing to the paraganglionic belt areas devoid of Betz-pyramids, the uniform multiform layer splits into a strongly pigmented ^pVIa and a more pallid ^pVIb.The subcentral region at the lowermost extremity of the central sulcus displays features of both frontal and parietal areas.The frontal region is mainly formed of equoteniate areas but comprises also a tongue-shaped internoteniate territory medially and an elongated externoteniate area laterally. Extended parts of the frontal region which abut upon the paraganglionic belt are endowed with unusually large and pigmentladen IIIc-pyramids. Pyramids of this type can be rarely encountered within the human isocortex but occur in great number in circumscribed specialized regions such as the temporal magnopyramidal region which represents probably the speech centre of Wernicke. Within the frontal lobe, two magnopyramidal regions can be distinguished. The superofrontal magnopyramidal region stretches out over large parts of the superior frontal convolution whereas the inferofrontal one is small and covers mainly posterior parts of the inferior frontal gyrus. As to its location, the superofrontal magnopyramidal region includes the supplementary motor region which is known to be involved in the performance of speech. On account of its unique structure and its location, the inferofrontal magnopyramidal region is considered to represent the morphological counterpart of the speech centre of Broca.     

Tranexamsäure und Endoprothetik: zwischen „off label use“ und „evidence-based medicine“

Die Anaesthesiologie -     

Transvenous Endomyocardial Biopsy: A Comparison of 2 Approaches

BackgroundEndomyocardial biopsy (EMB) is a well-established procedure for the diagnosis of specific myocardial diseases and represents the gold standard in monitoring allografts after heart transplantation. In our study, we compared 2 different approaches for harvesting EMB in order to optimize patient safety and efficacy of the procedure.MethodsAs a standard approach for harvesting EMB, a venous introducer sheath was inserted percutaneously via the internal jugular vein using the Seldinger technique. Thereafter, a bioptome was repeatedly introduced throughout this sheath into the right ventricle (RV), each time passing the tricuspid valve (TV). Alternatively, a coronary sinus catheter was inserted via an introducer sheath placed in the subclavian vein and only once was introduced into RV cavity. Hence, just a unique passage of TV was required. Thereafter, a bioptome was introduced via this catheter and precisely guided to the targeted biopsy site.ResultsA standard approach was used with 34 patients, and a modified technique was used with 37 patients. Patient characteristics were comparable in both cohorts, and analyses of peri-procedural parameters identified only marginal differences between the groups. Interestingly, the number of harvested tissue samples per procedure was higher in the modified approach compared to the standard approach. No complications occurred.ConclusionThe modified approach for EMB is a safe procedure. The facilitated bioptome-guidance and enhanced protection of TV may prevent periprocedural complications.     

Non–Guideline-concordant Treatment of Testicular Cancer Is Associated With Reduced Relapse-free Survival

Introduction

The management of testicular cancer (TC) requires a complex multimodal therapeutic approach. Despite the availability of regularly updated guidelines, non–guideline-concordant treatment of TC still occurs. The purpose of the present study was to evaluate the compliance patterns in diagnosis and therapy and their potential effects on patient outcomes with respect to the guidelines of the European Association of Urology.