Subcutaneous immunization with a novel immunogenic candidate (urease) confers protection against Brucella abortus and Brucella melitensis infections

Brucellosis is a world prevalent endemic illness that is transmitted from domestic animals to humans. Brucella spp. exploits urease for survival in the harsh conditions of stomach during the gastrointestinal infection. In this study, we examined the immune response and the protection elicited by using recombinant Brucella urease (rUrease) vaccination in BALB/c mice. The urease gene was cloned in pET28a and the resulting recombinant protein was employed as subunit vaccine. Recombinant protein was administered subcutaneously and intraperitoneally. Dosage reduction was observed with subcutaneous (SC) vaccination when compared with intraperitoneal (IP) vaccination. rUrease induced mixed Th1–Th2 immune responses with high titers of specific IgG1 and IgG2a. In lymphocyte proliferation assay, splenocytes from IP and SC‐vaccinated mice displayed a strong recall proliferative response with high amounts of IL‐4, IL‐12 and IFN‐γ production. Vaccinated mice were challenged with virulent Brucella melitensis, B. abortus and B. suis. The SC vaccination route exhibited a higher degree of protection than IP vaccination (p value ≤ 0.05). Altogether, our results indicated that rUrease could be a useful antigen candidate for the development of subunit vaccines against brucellosis.     

Structure function interface with sequential shortening of basal and apical components of the myocardial band

Objective: To mechanically test the intact cardiac structure to determine the sequence of contraction within the myocardial mass to try to explain ejection and suction. Methods: In 24 pigs (30–85 kg), segment shortening at the site of sonomicrometer crystals was continuously recorded. The ECG evaluated rhythm, and Millar pressure transducers measured intraventricular pressure and dP/dt. Results: Study of segment shortening defined a sequence of contraction within the myocardial mass, starting at the free wall of the right ventricle and on the endocardial side of the antero-septal wall of the left. Crystal location defined underlying contractile trajectory; transverse in right ventricle followed by basal posterior left ventricle, and from the endocardial anterior wall to the posterior apical segment and finally to the epicardial side of the anterior wall. Mean shortening fraction averaged 18±3%, with endocardial exceeding epicardial shortening by 5±1%. Epicardial segment crystal displacement followed endocardial shortening by 82±23 ms in the anterior wall, and finished 92±33 ms after endocardial shortening stopped, time frame that matches the interval of fast drop of ventricular pressure and the start of suction. Conclusions: Crystal shortening fraction sequence followed the rope-like myocardial band model to contradict traditional thinking, with two starting points of excitation–contraction, the right anterior free wall of the right ventricle, and the endocardial side of the anterior wall. Active suction may be due to active shortening of the epicardial fibers of the anterior wall, because relaxation was not detected when both mitral and aortic valves were closed during the interval previously termed ‘isovolumetric relaxation’.     

Pre-adaptation, adaptation and de-adaptation to high altitude in humans: hormonal and biochemical changes at sea level

High altitude residence is known to modify body biochemistry and hormone status. However, the effects of such a sojourn on these status observed at sea level both immediately and later after return are not as well established as are the effects of an intermittent acclimation. The aim of this study was therefore to investigate these changes. To achieve our objectives, nine subjects received intermittent acclimation at low pressure in a barometric chamber (8?h daily for 5 days, day 1 at 4500 m, day 5 at 8500 m) before an expedition to the Himalayas. Hormonal and biochemical changes were studied using samples of venous blood taken at sea level before and after acclimation, after return from the expedition and 1 and 2 months after descent. Concentrations of thyroid hormones, adrenaline, noradrenaline (NA), hormones of hydromineral metabolism (aldosterone, renin, arginine vasopressin, atrial natriuretic peptide) as well as prolactin, cortisol, insulin and endothelin 1 were measured. Biochemical measurements made were plasma osmolality, and concentrations of glucose, total cholesterol, total proteins, pre-albumin, transferrin, complement 3C, apolipoproteins A₁ and B and serum iron. Acclimation induced no alteration in hormone (except for NA with increases of about 1.5, fold P<0.05) and biochemistry data. After the expedition, hormone responses were characterized by a higher total triidothyronine concentration (+18%, P<0.05) while other hormones did not vary. A linear relationship was found between thyroid-stimulating-hormone and body mass changes after the expedition (r=0.67, P<0.05). The observed increased concentrations of plasma proteins and total cholesterol (P<0.05) could be related to the restoration of lean body mass. At 1 and 2 months after return, no changes in hormones were observed but a significant decrease in transferrin concentration was noticed. The higher serum iron concentration reported after 1 month (P<0.05) could have been the result of a physiological haemolysis. It was concluded that both acclimation and the expedition in the Himalayas affected hormone status and body biochemistry status even though the observed changes were slight and rapidly reversed.     

Use of amniotic grafts in the repair of gastroschisis

This article describes the use of amniotic grafts (AG) in the repair of large abdominal wall defects in newborns with gastroschisis. From 1988 to 1995, 22 newborns with gastroschisis underwent surgical repair. In 12 primary closure (PC) was performed; in 10 the abdominal wall defect was covered with an AG. A double layer of AG was used and the graft was additionally covered with a silastic silo in 8 cases. The overall mortality was 14%; 3 children died from necrotizing enterocolitis or sepsis after AG. However, the difference in mortality of newborns with PC versus AG was not statistically significant. Patient characteristics, the postoperative courses, nd the frequency of complications were similar after PC and AG. It is concluded that AG has no negative impact on the postoperative course and yields a low overall mortality. In our opinion there are several advantages in using the AG technique: it is an autoplastic material that is readily available without costs, reefing and removal is unnecessary, and there is a potentially low rate of adhesions.     

Hormone changes induced by 37.5-h head-down tilt (−6°) in humans

Endocrine regulation of hormones and electrolytes during 37.5 h of –6° head down tilt (HDT) was studied in 13 men. The acute effects of simulated weightlessness are today well documented, but no study has been made concerning the hormone changes between 12 h and 2 days of HDT. Plasma volume showed a maximal increase of 9.23 (SEM 1.97) % after 6.5 h (P<0.01) and had returned to prestudy levels after 13.5 h of HDT. From 1.5 h to 4 h of HDT, C-terminus and N-terminus atrial natriuretic peptide (ANP) concentrations in plasma were increased by about 50% (P<0.01) and thereafter declined to pre-HDT levels. Plasma renin activity (PRA) was decreased by 47% (P<0.05) after 4 h of HDT; PRA increased after 23.5 h to 60%; noradrenaline concentration decreased immediately and remained low up to 37.5 h. Diuresis and natriuresis were evident during the 1st day of HDT, resulting in a marked increase in the urinary Na⁺. These results showed that the initial hormone (ANP, PRA) changes during HDT did not last more than 13.5 h and that after 24 h a new state would seem to have been established to adapt the body to hypovolaemia.     

Sympathetic nervous activity and cardiovascular variability after a 3-day tail suspension in rats

The effects of a 3-day tail suspension on central and peripheral sympathetic activity were studied in rats by determining the in vivo noradrenaline (NA) turnover in the brain cell groups involved in central blood pressure control (A1, A2, A5 and A6) and in two peripheral organs, heart and kidneys. In addition, cardiovascular parameters and their variabilities were investigated by recording blood pressure (BP) and heart rate (HR) before and after suspension. These measurements were processed by spectrum analysis to assess the influence of tail suspension on autonomic balance. The NA turnover in the suspended rats was markedly reduced in A2 (–49%, P<0.01) and A5 (–38%, P<0.01) nuclei but unchanged in A1 and A6 cell groups compared with the control rats. Peripheral NA turnover was decreased in cardiac atria (–44%, P<0.001) and ventricles (–27%, P<0.01) while it was unchanged in kidneys after suspension. The BP, HR and their variabilities were similar in both groups of animals and showed no changes after suspension compared with baseline values. Spectrum analysis of BP and HR in our conscious suspended rats revealed no changes in power spectrum density or in peak frequencies. The discrepancy between the decrease in central sympathetic activity and the absence of changes in cardiovascular parameters after tail suspension raises the question of the validity of the tail suspended rat model when studying the cardiovascular deconditioning observed in humans after an exposure to actual or simulated weightlessness.