Central and peripheral neuroimmune responses: hyporesponsiveness during pregnancy

There are periods in the life of a healthy animal (including humans) when the febrile response to an immune challenge is suppressed. One such period is during late pregnancy, particularly around the time of parturition. In the 30 or so years since this 'febrile hyporesponsiveness' was first noted, much work has been done to investigate the mechanisms and adaptive significance of this phenomenon. In this review we present some insight into how and why the body deliberately re-programmes itself to develop smaller fevers in response to an immune challenge and therefore to be potentially less successful at fighting infection.     

Cloning and expression of arylalkylamine N-acetyltranferase-2 during early development and metamorphosis in the sole Solea senegalensis

The arylalkylamine N-acetyltransferase (AANAT) is a key enzyme in the rhythmic production of melatonin. Two Aanats are expressed in teleost fish, one retinal specific, Aanat1, and the other one pineal specific, Aanat2, being the latter the main enzyme responsible of the plasma nocturnal melatonin increase in fish. In anurans melatonin has been involved in metamorphosis through antagonizing thyroid hormone function; however, no available data reports a relationship between melatonin system and metamorphosis in fish. In this study, we have cloned the AANAT2 (SsAanat2) in a flatfish, Solea senegalensis, and studied its sites of expression and developmental expression pattern by in situ hybridization and Real Time PCR. These studies allowed us to demonstrate a specific signal in the pineal gland of sole larvae from 2 days post-fertilization (dpf), which was evident until post-metamorphosis. Immunohistochemical analysis on the hybridized slides showed that the sole pineal Aanat2 expressing cells corresponded to pineal photoreceptor cells. Real Time PCR was performed in animals kept under natural photoperiod and sampled at different stages from 0 to 21 dpf (including pre-, early-, middle- and late-metamorphic stages) and at midlight (ML) and middark (MD) daytimes. Sole Aanat2 expression was higher at MD than at ML from 2 dpf and at most developmental stages analyzed. The highest AANAT2 mRNA abundance was observed at 2 and 4 dpf. A significant 60-fold reduction in Aanat2 expression was seen just before metamorphosis demonstrating, for the first time in a vertebrate species, that the expression of pineal AANAT and thyroid hormones levels exhibit an inverse pattern during metamorphosis.     

The PACAP-regulated gene selenoprotein T is highly induced in nervous, endocrine, and metabolic tissues during ontogenetic and regenerative processes

Selenoproteins contain the essential trace element selenium whose deficiency leads to major disorders including cancer, male reproductive system failure, or autoimmune thyroid disease. Up to now, 25 selenoprotein-encoding genes were identified in mammals, but the spatiotemporal distribution, regulation, and function of some of these selenium-containing proteins remain poorly documented. Here, we found that selenoprotein T (SelT), a new thioredoxin-like protein, is regulated by the trophic neuropeptide pituitary adenylate cyclase-activating polypeptide (PACAP) in differentiating but not mature adrenomedullary cells. In fact, our analysis revealed that, in rat, SelT is highly expressed in most embryonic structures, and then its levels decreased progressively as these organs develop, to vanish in most adult tissues. In the brain, SelT was abundantly expressed in neural progenitors in various regions such as the cortex and cerebellum but was undetectable in adult nervous cells except rostral migratory-stream astrocytes and Bergmann cells. In contrast, SelT expression was maintained in several adult endocrine tissues such as pituitary, thyroid, or testis. In the pituitary gland, SelT was found in secretory cells of the anterior lobe, whereas in the testis, the selenoprotein was present only in spermatogenic and Leydig cells. Finally, we found that SelT expression is strongly stimulated in liver cells during the regenerative process that occurs after partial hepatectomy. Taken together, these data show that SelT induction is associated with ontogenesis, tissue maturation, and regenerative mechanisms, indicating that this PACAP-regulated selenoprotein may play a crucial role in cell growth and activity in nervous, endocrine, and metabolic tissues.     

Characterization of murine monoclonal antibodies directed against the Kell blood group glycoprotein

Murine monoclonal antibodies (MoAbs) were produced against the blood group KEL1 glycoprotein (93 kD component) immunopurified from human erythrocytes. One monoclonal antibody, 5A11 (IgGa, kappa), detects by immunoblotting a 93 and 184 kD component from KEL: 1,-2 or KEL: -1,2 red cell membrane preparations, separated by SDS polyacrylamide gel electrophoresis (PAGE) under non-reducing conditions. The 184 kD component was not detected under reducing conditions, suggesting that it represented a dimer of the 93 kD KEL glycoprotein. Neither the 93 nor the 184 kD could be detected from K0 or McLeod erythrocyte membrane preparations, indicating that the monoclonal antibody reacts with the KEL glycoprotein previously identified as a 93 kD species. Since this antibody does not agglutinate native or protease-treated erythrocytes, it is likely that it reacts with the cytoplasmic domain of the KEL glycoprotein. This was also substantiated by showing that 5A11 could immunoprecipitate the 93 kD component from intact membranes and inside-out vesicles but not from right-side-out vesicles. Immunostaining of membrane proteins prepared from human blood cells (platelets, lymphocytes, monocytes and granulocytes) and non-human erythrocytes revealed that the 93 kD molecule was only present on human red cells. Several other murine monoclonal antibodies obtained from the same fusion experiment gave identical results, but competition analyses on immunoblots indicated that these antibodies reacted with distinct epitopes on the KEL glycoprotein.     

Phrenic nerve stimulation in cardiac resynchronization therapy

In cardiac resynchronization therapy (CRT), the electrical impulse delivered by the left ventricular (LV) lead may incidentally cause phrenic nerve stimulation (PNS). The purpose of this state-of-the-art review is to describe the frequency, risk factors, and clinical consequences of PNS and to present the most recent options to successfully manage PNS. PNS occurs in 2 to 37 % of implanted patients and is not always detected in the supine position during implantation. Lateral and posterior veins are at higher risk of PNS than anterior veins, and apical positions are at higher risk of PNS than basal positions. The management of PNS discovered during implantation may include mapping the course of the target vein in order to find a PNS-free site, targeting another vein if available, and pacing with alternative configurations before changing the lead location. Non-invasive options for management of post-operative PNS depend on the difference between PNS and LV stimulation thresholds and include reducing the LV pacing output, automatic determination of LV stimulation threshold and minimal output delivery by the device, increasing the pulse duration, and electronic repositioning. New quadripolar leads allow to pace from different cathodes, and the multiple pacing configurations available have proved superior to bipolar leads in mitigating PNS. This electronic repositioning addresses almost all of the clinically relevant PNS and should markedly reduce the need for invasive lead repositioning or CRT abandon, which is actually the last option for 2 % of patients.     

Are the destructive neurosurgical techniques as effective as microvascular decompression in the management of trigeminal neuralgia?

BACKGROUND: There are no randomized controlled trials comparing TC, PTGC, and MVD for idiopathic TN at a single institution using quality criteria. The aim of the study was to assess the long-term outcome (efficiency and morbidity) of treated patients with one of these techniques in the same institution. METHODS: The authors present a retrospective study of 165 consecutive patients from 1983 to 2004. The inclusion criteria were drug-resistant idiopathic TN and intolerance to medical treatment. Three groups were set up according to the techniques used: group I (n = 73), treated by TC; group II (n = 41), treated by PTGC; group III (n = 51), treated by MVD. The main judgment criterion was pain relief. The second judgment criterion was morbidity. chi(2) or Fisher exact test, Kaplan-Meier, and log-rank were used for statistical analysis. RESULTS: The 3 groups were homogeneous according to age, duration of evolution, and pain topography. Concerning sex, groups I and II were different (women, 58%; vs. 37%; P = .021). The immediate efficiency for the 3 groups was, respectively, 96%, 94%, and 95% (NS). At 6 years follow-up, 70%, 77%, and 72% of the patients, respectively, remained pain-free (NS). As determined by the Kaplan-Meier survival curve, there was no difference between the 3 groups (log-rank, P = .867). Hypoesthesia was more frequent for PTGC (89%). CONCLUSIONS: In our study, we did not find MVD to be more effective than the other techniques. However, it had the lowest long-term complication rate, which is a strong argument in choosing this technique as the initial procedure for young and healthy patients. Percutaneous techniques, however, are still recommended in specific circumstances.     

Femoral head vascularisation in Legg-Calvé-Perthes disease: comparison of dynamic gadolinium-enhanced subtraction MRI with bone scintigraphy

Background. It has been reported that MRI using a dynamic gadolinium-enhanced subtraction technique can allow the early identification of ischaemia and the pattern of revascularisation in Legg-Calvé-Perthes (LCP) disease with increased spatial and contrast resolution. Therefore, dynamic gadolinium-enhanced subtraction (DGS) MRI may be a possible non-ionising substitute for bone scintigraphy. Objective. The purpose of this prospective study was to compare DGS MRI and bone scintigraphy in the assessment of femoral head perfusion in LCP disease. Materials and methods. Twenty-six DGS MR images and bone scintigraphies of 25 hips in 23 children were obtained at different stages of LCP disease; three stage I, 12 stage II, six stage III and five stage IV (Waldenström classification). The extent of necrosis, epiphyseal revascularisation pathways (lateral pillar, medial pillar, and/or transphyseal perfusion) and metaphyseal changes were analysed. Results. Total agreement between both techniques was noted in the depiction of epiphyseal necrosis (kappa=1), and metaphyseal abnormalities (kappa=0.9). DGS MRI demonstrated better revascularisation in the lateral (kappa=0.62) and medial pillars (kappa=0.52). The presence of basal transphyseal reperfusion was more conspicuous with MRI. Conclusions. DGS MRI allows early detection of epiphyseal ischaemia and accurate analysis of the different revascularisation patterns. These changes are directly related to the prognosis of LCP disease and can aid therapeutic decision making.