Perfusion of the septum of the rabbit with vasopressin antiserum enhances endotoxin fever

The septal region of the brains of conscious, adult, male New Zealand White rabbits were perfused by means of a push-pull system before and after an intravenous administration of bacterial pyrogen extracted from Salmonella abortus equi. Perfusion of the septal area with sucrose solution (260 mM) had no significant effect on the resulting fever (1.13 +/- 0.09 degrees C) when compared to a control fever without the push-pull perfusion (1.06 +/- 0.12 degrees C). Arginine vasopressin (AVP) added to the perfusing solution (20 micrograms/ml) caused a significant attenuation of the fever (0.81 +/- 0.20 degrees C). An antiserum specific to AVP when added to the perfusing solution resulted in a fever which was significantly greater (2.38 +/- 0.13 degrees C) than the control. Radioimmunoassay of perfusates collected from the control perfusions before and during fever showed that, as the body temperature rose in response to the pyrogen, the level of AVP in the perfusate collected from the septal area decreased. These results provide further evidence that AVP may act in the septal area of the brain to modulate the febrile response.     

Swimming capabilities of stoats and the threat to inshore sanctuaries

Stoats (Mustela erminea) are small carnivorous mammals which were introduced into New Zealand in the late nineteenth century, and have now become widespread invasive pests. Stoats have long been known to be capable of swimming to islands 1–1.5 km offshore. Islands further out have usually been assumed to be safe from invasion, therefore routine stoat monitoring on them has been considered un-necessary. Recent incursions, including a stoat found on Rangitoto Island (3 km offshore) in 2010, and another which was deduced to have reached Kapiti (5 km offshore) in 2009, along with distribution modelling and genetic studies, strongly support the proposition that stoats can swim much further than 1.5 km. Acceptance of this hypothesis depends on estimating the probability that such small animals could indeed swim so far unaided. This paper reports the results of a project designed to assist this debate by recording the paddling action, speed and minimal endurance of nine stoats observed (once each) swimming against an endless current in a flume at the Aquatic Research Centre, University of Waikato. Four of the five males and two of the four females could hold a position for at least 5 min against the maximum current available, averaging 1.36 ± 0.336 km/h. In steady swimming against a current of c. 1 km/h, they all used a rapid quadripedal paddling action (averaging 250 strokes/min, stronger with the spread forepaws). Four of the nine swam strongly for >1 h, including one female who covered 1.8 km in nearly 2 h non-stop. Results from such artificial conditions cannot be conclusive, but support suggestions that wild stoats could indeed swim much further than 1.5 km, hence we conclude that the “risk zone” for stoat reinvasions of inshore islands has been seriously under-estimated.     

Interleukin-7 deficiency in rheumatoid arthritis: consequences for therapy-induced lymphopenia

We previously demonstrated prolonged, profound CD4+ T-lymphopenia in rheumatoid arthritis (RA) patients following lymphocyte-depleting therapy. Poor reconstitution could result either from reduced de novo T-cell production through the thymus or from poor peripheral expansion of residual T-cells. Interleukin-7 (IL-7) is known to stimulate the thymus to produce new T-cells and to allow circulating mature T-cells to expand, thereby playing a critical role in T-cell homeostasis. In the present study we demonstrated reduced levels of circulating IL-7 in a cross-section of RA patients. IL-7 production by bone marrow stromal cell cultures was also compromised in RA. To investigate whether such an IL-7 deficiency could account for the prolonged lymphopenia observed in RA following therapeutic lymphodepletion, we compared RA patients and patients with solid cancers treated with high-dose chemotherapy and autologous progenitor cell rescue. Chemotherapy rendered all patients similarly lymphopenic, but this was sustained in RA patients at 12 months, as compared with the reconstitution that occurred in cancer patients by 3-4 months. Both cohorts produced naive T-cells containing T-cell receptor excision circles. The main distinguishing feature between the groups was a failure to expand peripheral T-cells in RA, particularly memory cells during the first 3 months after treatment. Most importantly, there was no increase in serum IL-7 levels in RA, as compared with a fourfold rise in non-RA control individuals at the time of lymphopenia. Our data therefore suggest that RA patients are relatively IL-7 deficient and that this deficiency is likely to be an important contributing factor to poor early T-cell reconstitution in RA following therapeutic lymphodepletion. Furthermore, in RA patients with stable, well controlled disease, IL-7 levels were positively correlated with the T-cell receptor excision circle content of CD4+ T-cells, demonstrating a direct effect of IL-7 on thymic activity in this cohort.     

An in situ study of predator aggregations on scallop (Pecten maximus (L.)) dredge discards using a static time-lapse camera system

The impact of demersal fishing gears on benthic habitats and species has been the subject of much attention recently, and suggestions have been made that scavenging epifaunal species may benefit at the population level from the additional food source provided by discards. This paper investigates some aspects of this process, including the relative attractiveness to predators of different discard species, and the role of damage in scavenger attraction. A time-lapse video system with a 1000 m long cable was positioned in an area closed to fishing, adjacent to the most heavily fished scallop (Pecten maximus) ground in the Irish Sea. A variety of undamaged and damaged by-catch animals were positioned in front of the camera, and the subsequent predator aggregations investigated. Densities of scavenger species up to 200 times that of the background population were observed, and aggregations of some species persisted for up to 3 days. The most frequently recorded scavengers, and therefore presumably those species most likely to benefit from discards as a food source, were: Asterias rubens L., Astropecten irregularis (Pennant), Liocarcinus spp Stimpson, Pagurus spp Fabricius and Callionymus lyra L. Predator attraction to apparently undamaged queen scallops, Aequipecten opercularis (L.), was almost as high as to damaged A. opercularis. Of all the prey species studied, queen scallops were the most attractive to scavengers. A directional relationship was found between the ambient water current and the arrival of the starfish, Asterias rubens.     

The role of arginine vasopressin in alcohol dependence and withdrawal

The development and maintenance of tolerance to the physiological and behavioral effects of repeated exposure to ethanol can be altered markedly by the presence of arginine vasopressin (AVP). In addition, AVP has been implicated in the etiology of convulsions, including those induced by exposure to high ambient temperatures. In light of these findings, experiments were conducted to determine the role, if any, that AVP might play in the pathogenesis of alcohol-withdrawal convulsions. Thirty-two male Long Evans (LE) rats and 32 age-matched male homozygous Brattleboro (DI) rats (genetically deficient in AVP) were exposed to ethanol vapor concentrations adjusted to maintain blood alcohol levels of each rat at 150–350 mg/dl. Following at least 5 days of ethanol exposure, the animals were withdrawn. From 3–24 hr after cessation of ethanol administration, withdrawal severity was assessed by observing the response of each animal to a 60–120 sec period of auditory stimulation. No significant differences were observed in either latency to onset or severity of the convulsions in LE and DI rats upon ethanol withdrawal. Thus, alcohol-withdrawal convulsions, unlike hyperthermia-induced convulsions, may be mediated by a neurochemical substrate other than AVP.     

Vasopressin and fever: evidence supporting the existence of an endogenous antipyretic system in the brain

Vasopressin administered into the ventral septum exerts a dose-related antipyresis. This site of action is similar in a number of species. The fever-reducing properties of vasopressin are both site and neuropeptide specific. Evidence supporting a role for endogenous vasopressin in fever suppression is the demonstration that the release of the peptide from the ventral septal area is altered during fever: the amount released correlates negatively with febrile changes in body temperature. In addition, changes in the concentration of vasopressin in the septum and amygdala have been demonstrated immunocytochemically during fever: an activation of vasopressinergic neurons occurs which is similar to that observed in pregnant animals at term when fever is absent. Specific antibodies directed against vasopressin or specific vasopressin antagonist analogues (e.g., d(CH2)5Tyr(Me)AVP) enhanced the febrile response to a pyrogen challenge when injected into the ventral septum. The same antagonist also can antagonize the antipyretic effect of exogenously administered vasopressin. The use of relatively specific antagonists and agonists of vasopressin, directed against the V1 and V2 subtypes of the peripheral vasopressin receptor, suggests that the central receptor responsible for the antipyretic effect of vasopressin may resemble the V1 subtype. Recent experiments using electrophysiological techniques have demonstrated the existence of thermoresponsive units in the ventral septal area whose activity may be altered by vasopressin which is possibly derived from the paraventricular nucleus and bed nucleus of the stria terminalis.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of stopping smoking for 48 hours on oxygen availability from the blood: a study on pregnant women.

The effects of stopping smoking for 48 hours on factors governing the availability of oxygen from the blood--that is, carboxyhaemoglobin (COHb), haemoglobin-oxygen (HbO2) affinity, and haemoglobin concentration--were measured in women in the last trimester of pregnancy. Three groups were studied: smokers, smokers who stopped smoking for 48 hours, and non-smokers. The 22 smokers had higher initial COHb values and greater HbO2 affinity than the 10 non-smokers, but their total haemoglobin concentrations were also higher, so that their oxygen availability was not significantly reduced. In the 11 smokers who stopped the reduction in COHb and decrease in HbO2 affinity led to a significant increase of 8% in "available oxygen" in 48 hours. Since even small improvements in oxygen delivery to the tissues may confer critical benefit to the fetus, particularly during labour or when exposed to general anaesthesia, smoking should be discouraged for 48 hours before elective deliveries. The same consideration might reasonably be applied to patients undergoing general anaesthesia for all elective operations.     

Synthesis and SAR of novel CXCR4 antagonists that are potent inhibitors of T tropic (X4) HIV-1 replication

An early lead from the AMD070 program was optimized and a structure-activity relationship was developed for a novel series of heterocyclic containing compounds. Potent CXCR4 antagonists were identified based on anti-HIV-1 activity and Ca²⁺ flux inhibition that displayed good pharmacokinetics in rat and dog.