High-frequency oscillatory ventilation does not decrease endothelin release in lung-lavaged rabbits

High-frequency oscillatory ventilation (HFO) has been shown to reduce lung injury and pulmonary arterial pressure (PAP). We hypothesized that HFO leads to decreased endothelin 1 (ET-1) and endothelin 3 (ET-3) release when compared to conventional mechanical ventilation (CMV) in lung-lavaged rabbits. Design: Prospective, randomized, controlled animal study. In 26 adult New Zealand White Rabbits ventilated by CMV or HFO under hypoxemic and normoxemic conditions after lung lavage (CMV-hypo: n=5; CMV-normo: n=8; HFO-hypo: n=7; HFO-normo: n=6) we recorded systemic and PAP, measured blood gases, ET-1 and ET-3 and calculated intrapulmonary venous admixture during a 4-h experiment. ET-1 was significantly increased after lavage (p<0.05) with no further increase until the end of the experiment. Neither pulmonary arterial nor systemic arterial ET-1 differed between CMV and HFO or between hypoxemia and normoxemia. Systemic arterial ET-3, however, was significantly higher in HFO-hypo than in the other two groups ventilated under normoxemic conditions at the end of the experiment (HFO-hypo vs. CMV-normo, p<0.05; HFO-hypo vs. HFO-normo, p<0.05). PAP showed a continuous increase in all groups (p<0.05). We did not find any correlation between PAP and ET-1 or ET-3. Intrapulmonary venous admixture increased in animals ventilated under hypoxemic conditions, whereas it decreased after lung lavage in those ventilated under normoxemic conditions until the end of the experiment (HFO-normo, p<0.05). Conclusions: This study suggests that HFO does not decrease ET-1 and ET-3 release compared to CMV in lung-lavaged rabbits. Hypoxemia, however, may increase ET-3 release from the lungs, leading to an increased intrapulmonary shunt.     

Sympathetic innervation does not contribute to glycerol release in ischemic flaps

Abstract

Background. Extracellular glycerol as detected by microdialysis has been used as a surrogate marker for (ischemic) tissue damage and cellular membrane breakdown in the monitoring of free microvascular musculocutaneous flaps. One confounding factor for glycerol as a marker of ischemic cell damage is the effect of lipolysis and associated glycerol release as induced by sympathetic signalling alone. We hypothesized that extracellular glycerol concentrations in a microvascular flap with sympathetic innervation would be confounded by intact innervation per se as compared to denervated flap. Clinical relevance is related to the use of both free and pedicled flaps in reconstructive surgery. We tested the hypothesis in an experimental model of microvascular musculocutaneal flaps. Methods. Twelve pigs were anesthetized and mechanically ventilated. Two identical rectus abdominis musculocutaneal flaps were raised for the investigation. In the A-flaps the adventitia of the artery and accompanying innervation was carefully stripped, while in the B-flaps it was left untouched. Flap ischemia was induced by clamping both vessels for 60 minutes. The ischemia was confirmed by measuring tissue oxygen pressure, while extracellular lactate to pyruvate ratio indicated the accompanying anaerobic metabolism locally. Results. Intramuscular and subcutaneal extracellular glycerol concentrations were measured by microdialysate analyzer. Contrary to our hypothesis, glycerol concentrations were comparable between the two ischemia groups at 60 minutes (p =?0.089, T-test). Conclusions. In this experimental model of vascular flap ischemia, intact innervation of the flap did not confound ischemia detection by glycerol. Extrapolation of the results to clinical setting warrants further studies.     

High-frequency oscillatory ventilation does not decrease endothelin release in lung-lavaged rabbits

High-frequency oscillatory ventilation (HFO) has been shown to reduce lung injury and pulmonary arterial pressure (PAP). We hypothesized that HFO leads to decreased endothelin 1 (ET-1) and endothelin 3 (ET-3) release when compared to conventional mechanical ventilation (CMV) in lung-lavaged rabbits. DESIGN: Prospective, randomized, controlled animal study. In 26 adult New Zealand White Rabbits ventilated by CMV or HFO under hypoxemic and normoxemic conditions after lung lavage (CMV-hypo: n = 5; CMV-normo: n = 8; HFO-hypo: n = 7; HFO-normo: n = 6) we recorded systemic and PAP, measured blood gases, ET-1 and ET-3 and calculated intrapulmonary venous admixture during a 4-h experiment. ET-1 was significantly increased after lavage (p < 0.05) with no further increase until the end of the experiment. Neither pulmonary arterial nor systemic arterial ET-1 differed between CMV and HFO or between hypoxemia and normoxemia. Systemic arterial ET-3, however, was significantly higher in HFO-hypo than in the other two groups ventilated under normoxemic conditions at the end of the experiment (HFO-hypo vs. CMV-normo, p < 0.05; HFO-hypo vs. HFO-normo, p < 0.05). PAP showed a continuous increase in all groups (p < 0.05). We did not find any correlation between PAP and ET-1 or ET-3. Intrapulmonary venous admixture increased in animals ventilated under hypoxemic conditions, whereas it decreased after lung lavage in those ventilated under normoxemic conditions until the end of the experiment (HFO-normo, p < 0.05). CONCLUSIONS: This study suggests that HFO does not decrease ET-1 and ET-3 release compared to CMV in lung-lavaged rabbits. Hypoxemia, however, may increase ET-3 release from the lungs, leading to an increased intrapulmonary shunt.     

Sympathetic innervation does not contribute to glycerol release in ischemic flaps

Abstract Background. Extracellular glycerol as detected by microdialysis has been used as a surrogate marker for (ischemic) tissue damage and cellular membrane breakdown in the monitoring of free microvascular musculocutaneous flaps. One confounding factor for glycerol as a marker of ischemic cell damage is the effect of lipolysis and associated glycerol release as induced by sympathetic signalling alone. We hypothesized that extracellular glycerol concentrations in a microvascular flap with sympathetic innervation would be confounded by intact innervation per se as compared to denervated flap. Clinical relevance is related to the use of both free and pedicled flaps in reconstructive surgery. We tested the hypothesis in an experimental model of microvascular musculocutaneal flaps. Methods. Twelve pigs were anesthetized and mechanically ventilated. Two identical rectus abdominis musculocutaneal flaps were raised for the investigation. In the A-flaps the adventitia of the artery and accompanying innervation was carefully stripped, while in the B-flaps it was left untouched. Flap ischemia was induced by clamping both vessels for 60 minutes. The ischemia was confirmed by measuring tissue oxygen pressure, while extracellular lactate to pyruvate ratio indicated the accompanying anaerobic metabolism locally. Results. Intramuscular and subcutaneal extracellular glycerol concentrations were measured by microdialysate analyzer. Contrary to our hypothesis, glycerol concentrations were comparable between the two ischemia groups at 60 minutes (p =?0.089, T-test). Conclusions. In this experimental model of vascular flap ischemia, intact innervation of the flap did not confound ischemia detection by glycerol. Extrapolation of the results to clinical setting warrants further studies.     

The interleukin-6 G(-174)C promoter polymorphism does not determine plasma interleukin-6 concentrations in experimental endotoxemia in humans

BACKGROUND: Interleukin 6 (IL-6) is a pleiotropic cytokine that plays an essential role in the pathogenesis of acute and chronic infections. As the role of the IL-6 G(-174)C polymorphism in determining serum concentrations of IL-6 is controversial, we studied the genotype-specific IL-6 response in a well-standardized model of systemic inflammation. METHODS: A total of 76 healthy young males (age range, 19-35 years) received a single bolus of 2 ng/kg endotoxin [lipopolysaccharide (LPS)] intravenously. Plasma IL-6 was measured by enzyme immunoassay at 0, 2, 6, and 24 h after LPS infusion, and the IL-6 promoter genotype was analyzed by a mutagenic separated PCR assay. RESULTS: IL-6 increased 300-fold 2 h after LPS challenge and returned almost to normal within 24 h. Neither basal IL-6 nor the IL-6 response to LPS was significantly affected by the IL-6 promoter genotype. CONCLUSIONS: The IL-6 G(-174)C promoter polymorphism does not significantly influence basal concentrations of IL-6 or peak IL-6 in human endotoxemia.     

Poly-L-aspartic acid does but triiodothyronine does not protect against gentamicin-induced cytotoxicity in the porcine kidney cell line LLC-PK1.

This study investigated the protective effect of thyroid hormone and poly-L-aspartic acid (PAA) in an in vitro model of gentamicin nephrotoxicity. LLC-PK1 porcine renal cells were grown in Medium 199 supplemented with either fetal bovine serum or thyroid hormone-depleted fetal bovine serum. After a preincubation with or without 30 nM L-triiodothyronine for 3 days, or 0.1 mM PAA for 1 hr, cells were coincubated with 1 mM gentamicin for an additional 3 days. Determinations were made of the following indicators of cell damage and/or viability: the numbers of detached dead cells, the total lactate dehydrogenase activity and its percentage release and gamma-glutamyl transpeptidase activity. Preincubation with L-triiodothyronine did not protect from gentamicin-induced cell death but did reduce cellular accumulation of gentamicin (3.2 +/- 0.8 micrograms/mg of protein vs. 5.2 +/- 1.8 micrograms/mg of protein in controls; P less than .05). In contrast, preincubation with 0.1 mM PAA decreased gentamicin-induced cell death (gentamicin: 685 +/- 416% of control dead cells and 487 +/- 48% of control lactate dehydrogenase release; PAA + gentamicin: 164 +/- 63% of control dead cells and 257 +/- 85% of control lactate dehydrogenase release; P less than .05) but failed to attenuate inhibition by gentamicin of gamma-glutamyl transpeptidase activity (gentamicin: 69 +/- 7% of control; PAA+gentamicin: 76 +/- 3% of control) and failed to alter cellular gentamicin levels. Protection against gentamicin nephrotoxicity by L-triiodothyronine was not demonstrated in LLC-PK1 cells, indicating that its protective effect in vivo is likely due to a systemic effect of the hormone.(ABSTRACT TRUNCATED AT 250 WORDS)     

14例结节性淋巴细胞为主型霍奇金淋巴瘤患者的临床病理特征与疗效分析

目的 探讨结节性淋巴细胞为主型霍奇金淋巴瘤(NLPHL)患者的临床病理特征及疗效.方法 收集14例NLPHL患者的临床资料,对其临床病理特征及近、远期疗效进行相关性分析.结果 14例患者均为初治者,男、女各7例,中位发病年龄38(13～ 54)岁,中位随访时间为55.5(23～189)个月.发病率占同期霍奇金淋巴瘤(HL)的6.3％(14/223).免疫组织化学检查结果示14例患者CD20均呈(+)/弱(+),CD30均(-),仅1例患者呈CD15弱(+).14例患者中13例因自觉浅表淋巴结肿大就诊,所有患者惰性起病,病情进展缓慢.7例患者采用单纯化疗,7例患者采用放、化疗联合治疗.14例患者均有效,其中完全缓解(CR)+未证实的CR(CRu) 12例.5年无疾病生存率为85.7％,5年总生存率为100.0％.单纯化疗与放、化疗联合治疗相比,不同的化疗方案相比,其近、远期疗效差异均无统计学意义(P值均＞0.05).结论 NLPHL患者瘤细胞呈CD20(+)/弱(+),CD30(-),极少数患者呈CD15弱(+).NLPHL在HL患者中所占比例低,以中青年患者多见,起病缓慢,与经典型HL患者相比疗效较好.     

Dopamine does not correct oxygen consumption/oxygen delivery relation abnormality during vasomotor shock induced by interleukin-1beta

We previously showed that interleukin 1beta (IL-1beta) induces vasomotor shock and impairs the oxygen consumption (VO2)/oxygen delivery (DO2) relation by increasing the slope of the supply-independent line in rabbits. In the present study, we investigated the inotropic effect of dopamine on the VO2/DO2 abnormality induced by IL-1beta. Twelve rabbits were divided into two groups (n = 6, each) and were given 10 microg/kg of IL-1beta or saline (control) intravenously. After baseline measurements were obtained, dopamine was infused continuously at a rate of 20 microg/kg/min throughout the study in both groups. All rabbits were subjected to stepwise cardiac tamponade to reduce the DO2 to <5 mL/min/kg by inflation of a handmade balloon placed into the pericardial sac. The VO2/DO2 relation was then analyzed by the dual-line method. Dopamine failed to correct the IL-1beta-induced decrease in mean arterial pressure to the baseline level. Dopamine significantly increased cardiac index in both groups, resulting in significant increases in DO2 (IL-1beta, 28.5 +/- 6.0 mL/min/kg from baseline 24.1 +/- 3.5 mL/min/kg; control, 27.7 +/- 2.9 mL/min/kg from baseline 22.9 +/- 2.9 mL/min/kg), but did not affect VO2 (IL-1beta, 10.0 +/- 0.5 mL/min/kg from baseline 9.9 +/- 0.7 mL/min/kg; control, 10.2 +/- 0.4 mL/min/kg from baseline 10.2 +/- 0.2 mL/min/kg). The IL-1beta group showed a significantly greater supply-independent line slope than that of controls (IL-1beta, y = 0.14x + 6.3; control, y = 0.06x + 8.6) during stepwise decreases in DO2. These results indicate that continuous infusion of dopamine at 20 microg/kg/min increases DO2 but does not correct the vasomotor disturbance or VO2/DO2 abnormality caused by IL-1beta.     

Pancreatic islet production of murine interleukin-10 does not inhibit immune-mediated tissue destruction.

IL-10 inhibits macrophage-dependent antigen presentation, cytokine production, and generation of allospecific cells in vitro. These findings have lead to the widespread expectation that IL-10 may be a useful immunosuppressive agent to inhibit allograft rejection or autoimmunity in vivo. We used two experimental paradigms to study effects of murine IL-10 on in vivo immune responses. First, fetal pancreata or adult pancreatic islets from transgenic mice expressing IL-10 in pancreatic beta cells (Ins-IL-10 mice) were grafted across the MHC barrier to examine if IL-10 could inhibit allograft rejection. Second, Ins-IL-10 mice were crossed with transgenic mice expressing lymphocytic choriomeningitis virus (LCMV) antigens in pancreatic beta cells. These mice were infected with LCMV to elicit autoimmune diabetes, allowing us to ask if IL-10 protects islets from autoimmune destruction. We observed that allografts from IL-10-transgenic donors were rejected with comparable kinetics to the rejection of control nontransgenic allografts, indicating that IL-10 does not inhibit allograft rejection. After LCMV infection, IL-10 and LCMV antigen double transgenic mice developed diabetes earlier than LCMV antigen single transgenic littermates, suggesting that IL-10 does not inhibit islet antigen presentation or recognition. Our results contrast to in vitro observations and suggest that IL-10 cannot overcome immune-mediated tissue destruction within the pancreas.     

Heliox does not improve FEV1 in acute asthma patients

Thirteen patients with an acute exacerbation of asthma and pre-treatment FEV1 between 20%–60% of predicted were tested to determine whether a blend of 70:30, helium:oxygen (heliox) improved FEV1. No pre-treatment with bronchodilators occurred. The change in absolute and predicted FEV1 was measured after five minutes of breathing heliox. It was found that the absolute FEV1 during heliox was not significantly different from the absolute FEV1 before heliox. The difference between the absolute FEV1 during and before heliox was found to be -0.04 l. The percent predicted FEV1 during heliox was 40.8% ± 13.0% vs. 41.5% ± 11.9% before heliox. The difference between the percent predicted FEV1 during and before heliox was found to be −0.7%. We conclude that 70:30 heliox does not improve FEV1 in these patients.     

Plateletpheresis does not cause long-standing platelet-derived growth factor release into the donor blood

BACKGROUND: Recently, long-standing elevations of soluble growth factors released from platelets (PLTs) after contact with artificial surfaces during dialysis were described. They could be jointly responsible for the high frequency of death from cardiovascular diseases in dialysis patients. There are no comparable data on the extent and the duration of a growth factor release by plateletpheresis procedures. STUDY DESIGN AND METHODS: A total of 37 plateletpheresis procedures were performed with two different devices. PLT-derived growth factor (PDGF) isoform AB, transforming growth factor (TGF)-beta1, and beta-thromboglobulin (beta-TG) were measured in the donors' plasma samples, and PLT activation and function were measured by cytometry and aggregometry before and after plateletpheresis and 1 and 24 hours later. RESULTS: Before apheresis, the following mean plasma levels were found: beta-TG, 98.6 +/- 37.3 IU per mL; PDGF-AB, 71.5 +/- 38.5 pg per mL; and TGF-beta1, 2.24 +/- 0.80 ng per mL. At the end of the apheresis procedures, the mean PDGF-AB level had increased by a factor of 1.8 (p < 0.05). One hour later, the mean PDGF-AB level had normalized again. No significant change in the levels of beta-TG and TGF-beta1 was found by the apheresis procedures. There was no influence of the blood cell separator type on the results. CONCLUSION: Only a slight and rapidly reversible increase in soluble PDGF-AB was found during plateletpheresis and no increase in soluble TGF-beta1 and beta-TG was found. This change should not be harmful to the donor.     

Rituximab does not reset defective early B cell tolerance checkpoints

Type 1 diabetes (T1D) patients show abnormalities in early B cell tolerance checkpoints, resulting in the accumulation of large numbers of autoreactive B cells in their blood. Treatment with rituximab, an anti-CD20 mAb that depletes B cells, has been shown to preserve β cell function in T1D patients and improve other autoimmune diseases, including rheumatoid arthritis and multiple sclerosis. However, it remains largely unknown how anti–B cell therapy thwarts autoimmunity in these pathologies. Here, we analyzed the reactivity of Abs expressed by single, mature naive B cells from 4 patients with T1D before and 52 weeks after treatment to determine whether rituximab resets early B cell tolerance checkpoints. We found that anti–B cell therapy did not alter the frequencies of autoreactive and polyreactive B cells, which remained elevated in the blood of all patients after rituximab treatment. Moreover, the limited proliferative history of autoreactive B cells after treatment revealed that these clones were newly generated B cells and not self-reactive B cells that had escaped depletion and repopulated the periphery through homeostatic expansion. We conclude that anti–B cell therapy may provide a temporary dampening of autoimmune processes through B cell depletion. However, repletion with autoreactive B cells may explain the relapse that occurs in many autoimmune patients after anti–B cell therapy.     

The long-term maintenance of cytotoxic T cell memory does not require persistence of antigen

I have used the transfer of primed lymphocytes into syngeneic irradiated recipients to investigate whether the persistence of antigen is required in the long-term maintenance of cytolytic T cell memory to influenza virus. Animals were immunized with influenza virus (A/WSN) and used 17 wk later as either donors for T cells or as lethally irradiated recipients. Naive age-matched mice served as controls. At intervals of 4, 8, 16, and 25 wk after T cell transfer, experimental and control groups were immunized with a heterologous virus (A/JAP) and splenocytes tested for lytic activity to influenza virus 3 and 6 d after immunization. Lytic activity 3 d after infection (a property exclusive to a memory cytotoxic T cell response) (Effros, R. B., J. Bennink, and P. C. Doherty. 1978. Cell. Immunol. 36:345.; and Hill, A. B., R. V. Blanden, C. R. Parrish, and A. Mullbacher. 1992. Immunol. Cell Biol. 70:259), was only observed by primed and naive irradiated recipients reconstituted with memory T cells. No day 3 responses were observed when naive T cells were transferred into irradiated primed or unprimed recipients. These observations demonstrate that cytolytic T cell memory to influenza virus is long lived in the absence of antigen.     

Increased spontaneous production of interleukin-1 together with inhibitory activity in systemic sclerosis

1. Increased spontaneous production of interleukin-1, measured as lymphocyte-activating factor activity, was seen in unstimulated monocytes from systemic sclerosis patients. 2. Inhibitory activity to interleukin-1 was seen in both normal and patient monocyte supernatants. 3. Inhibitory activity was significantly higher in unstimulated and stimulated monocyte supernatants from systemic sclerosis patients. 4. The net effect was an apparent decrease in lymphocyte-activating factor activity in the monocyte supernatants from systemic sclerosis patients. 5. These findings suggest a possible mechanism by which collagen deposition could be enhanced, thereby giving rise to the extensive fibrosis characteristic of systemic sclerosis.     

Lentivirus-mediated gene transfer of viral interleukin-10 delays but does not prevent cardiac allograft rejection

Human immunodeficiency virus (HIV)-based lentiviral vectors expressing viral interleukin-10 (vIL-10) were used to transduce rat cardiac allografts with the aim of extending graft survival. vIL-10 expression was first shown, by RT-PCR, to persist in transduced heart isografts for at least 28 days after transduction. Cardiac transplants were performed in a fully allogeneic rat strain combination (Lewis to DA); allografts transduced by vectors expressing vIL-10 showed significantly prolonged survival (14.5 vs 7.5 days median survival time). Mixed lymphocyte reactions (MLRs) were used to determine the influence, in vitro, of vIL-10 on alloantigen-induced T-cell proliferation. Bioactive vIL-10, produced by DA rat aortic endothelial cells transduced with HIV-PGK-vIL-10, was added to MLRs at different time points and lymphocyte proliferation was assessed by uptake of [3H]thymidine. T-cell proliferation was inhibited by >80% when vIL-10 was added to the MLR at day 1, 2 or 3 of coculture. The inhibitory effect was significantly decreased when addition of vIL-10 was delayed until day 4 or 5 (47 and 35% inhibition, respectively). The extended graft survival time is comparable to that using adenoviral vectors delivering vIL-10 in a similar rat strain combination. The limited improvement in survival may be due to lack of inhibition of the early phase of the alloimmune response as suggested by in vitro studies confirming that maximum suppression of the MLR by vIL-10 can only be achieved if the cytokine is present at the initiation of alloimmune recognition. The delay in expression of vIL-10 from the lentiviral vector means that protocols must be developed to suppress the early stages of alloimmune stimulation before vIL-10 is produced.     

Angiotensin II increases the release of endothelin-1 from human cultured endothelial cells but does not regulate its circulating levels

We investigated the effect of angiotensin II on endothelin-1 secretion in vitro and in vivo. In vivo, angiotensin II was given intravenously to 23 essential hypertensive and 8 control subjects according to different protocols: Study A, 1.0 ng x min-1 x kg-1 and 3.0 ng x min-1 x kg-1 angiotensin II for 30 min each; Study B, 1.0 ng x min-1 x kg-1 and 3.0 ng x min-1 x kg-1 angiotensin II for 120 min each; Study C, 3.0 ng x min-1 x kg-1 angiotensin II for 30 min followed by a dose increment of 3.0 ng x min-1 x kg-1 every 30 min until mean blood pressure levels increased by 25 mmHg; Study D, 1.0 ng x min-1 x kg-1 followed by 3.0 ng x min-1 x kg-1 angiotensin II for 60 min each on two different NaCl diets (either 20 mmol NaCl/day or 220 mmol NaCl/day, both for 1 week). In all in vivo studies neither plasma nor urine endothelin-1 levels changed with angiotensin II infusion. In contrast, angiotensin II (10(-9), 10(-8), 10(-7) mol/l) stimulated endothelin-1 secretion from cultured human vascular endothelial cells derived from umbilical cord veins in a time- and dose-dependent manner. The in vitro angiotensin II effects were abolished by candesartan cilexetil, an inhibitor of the membrane-bound AT1 receptor, and also by actinomycin D, an RNA synthesis inhibitor, and cycloheximide, a protein synthesis inhibitor, indicating that endothelin-1 release depended on AT1 receptor subtype and de novo protein synthesis. Our findings indicate that angiotensin II regulates endothelin-1 release by cultured endothelial cells through an AT1 receptor-dependent pathway, but does not influence circulating endothelin-1 levels in vivo.     

The C-terminal fragment of big endothelin-1 does not potentiate the vasoactive effects of endothelin-1

The aim was to study the cardiovascular effects of the C-terminal (22–38) fragment of big endothelin-1, which is produced by the cleavage of big endothelin-1 (big ET-1) to endothelin-1 (ET-1). An intravenous infusion of the (22–38) fragment (4, 8 and 12 pmol kg^?1 min^?1, each dose for 10 min) was given to 10 healthy subjects. Four control subjects received 0·9% saline. Two additional subjects received ET-1 (0·2 and 4 pmol kg^?1 min^?1, each dose for 20 min) alone or combined with an equimolar infusion of the (22–38) fragment on two separate occasions. The fragment infusion did not alter heart rate, mean arterial blood pressure, cardiac output, systemic or pulmonary vascular resistance, splanchnic, cerebral or forearm blood flow. Renal blood flow showed a slight fall (11%, P<0·001) in the fragment group of the same magnitude as in a previous control study. After the fragment infusion, a decrease in mean pulmonary arterial pressure (MPAP) by 12% (P<0·01) and in pulmonary capillary wedge pressure (PCWP) by 31% (P<0·001) was noted, which did not differ from the pulmonary pressures in the saline-infused control group. The (22–38) fragment, when combined with ET-1, was not able to modify the effects of ET-1 on heart rate, mean arterial blood pressure, splanchnic and renal blood flow. Consequently, the exogenous (22–38) fragment does not seem to cause any significant cardiovascular effects in healthy humans.     

The absence of interleukin 1 receptor-related T1/ST2 does not affect T helper cell type 2 development and its effector function

T1/ST2, an orphan receptor with homology with the interleukin (IL)-1 receptor family, is expressed constitutively and stably on the surface of T helper type 2 (Th2) cells, but not on Th1 cells. T1/ST2 is also expressed on mast cells, which are critical for Th2-mediated effector responses. To evaluate whether T1/ST2 is required for Th2 responses and mast cell function, we have generated T1/ST2-deficient (T1/ST2(-/-)) mice and examined the roles of T1/ST2. Naive CD4(+) T cells isolated from T1/ST2(-/-) mice developed to Th2 cells in response to IL-4 in vitro. T1/ST2(-/-) mice showed normal Th2 responses after infection with the helminthic parasite Nippostrongylus brasiliensis as well as in the mouse model of allergen-induced airway inflammation. In addition, differentiation and function of bone marrow-derived cultured mast cells were unaffected. These findings demonstrate that T1/ST2 does not play an essential role in development and function of Th2 cells and mast cells.     

Low-concentration morphine infusion does not compromise packed red blood cell transfusion

Regulations currently prohibit co-administration (through the same line) of red blood cell transfusions with continuous morphine infusions for pain management, resulting in additional intravenous access or interrupted analgesic therapy in seriously ill children. Packed cells that had been in contact with morphine 0.1 or 1.0 mg/mL and infused through a mock central venous catheter system showed no evidence of hemolysis when compared with control samples. There is thus no need to interrupt analgesic therapy or start another venous access line in order to give a coincident blood transfusion.