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1.
The effect of pretreatment with cyclosporine on liver preservation was studied using a rat liver transplant model. In a preliminary 1-week survival study, 59 liver transplants were performed. In group A, neither donors nor recipients were treated. In group B, the recipients were pretreated by a 3-day course of CsA (10 mg/kg/day p.o.), but the donors were untreated. In group C, the donor rats were pretreated for 3 days with the same doses of CsA as in group B, but the recipients were not treated. The donor livers in each group were stored for 12 hr at 4 degrees C with Eurocollins solution and transplanted to the recipients. The CsA pretreatment to recipients (group B) significantly improved 1-week survival (57.1%, 8/14, P less than 0.01 versus control group A; 0%, 0/14 or group C; 14.3%, 2/14). To study lipid peroxidation and morphology, 72 rat livers were studied in 9 groups. In summary, CsA pretreatment to recipients resulted in suppression of the increase in MDA levels and amelioration of endothelial injury after transplantation. On the other hand, donor pretreatment exerted dual effects on the grafts; it ameliorated endothelial injury after reperfusion, but its hepatotoxic action exacerbated hepatocellular damage during hypothermic storage. Our study suggests that CsA pretreatment, particularly to recipients, is beneficial in liver preservation for hepatic transplantation. The mechanisms are discussed with regard to ischemia/reperfusion injury to hepatic endothelium. 相似文献
2.
Takahiro Ishii Yang-Il Kim Katsunori Kawano Toshiro Tatsuma Tatsuo Shimada Seigo Kitano 《Journal of Hepato-Biliary-Pancreatic Surgery》1999,6(3):267-274
Mechanisms by which an immunosuppressant (cyclosporine, CsA) ameliorates warm ischemic injury of the liver were studied.
Female Sprague-Dawley rats were subjected to 60-min normothermic liver ischemia. Animals were assigned to one of two groups:
group I, controls with vehicle treatment; group II, treatment with CsA (10 mg/kg). CsA was given orally for 4 consecutive
days prior to the induction of hepatic ischemia. In addition to a survival study, plasma levels of endotoxin, serum activity
of tumor necrosis factor-α (TNF), and serum levels of aminotransferases were measured in blood samples collected from the
suprahepatic vena cava, and hepatic ultrastructural alterations were examined under an electron microscope. The 7-day survival
rate was significantly higher in the CsA-treated animals. In the control group, serum TNF levels were elevated following reperfusion
and peaked at 3 h. When the values at 3 h post reflow were compared, the animals given CsA had significantly lower levels
of TNF (170.0 ± 30.5 pg/ml for group I, 67.6 ± 13.7 for group II, mean ± SEM; P < 0.05). The sinusoidal lining cells and hepatocytes were drastically destroyed at 6 h post reflow in the control group,
although the degree of injury at 1–3 h was less severe. On the other hand, the endothelium and parenchymal liver cells in
the CsA-treated group were well preserved at 6 h in comparison with those in the control group. Our data suggest that modulation
of TNF production is one of the mechanisms through which CsA prevents the exacerbation of ischemia/reperfusion injury of the
liver.
Received for publication on Aug. 12, 1998; accepted on Feb. 2, 1999 相似文献
3.
The Effect of Surgically Induced Weight Reduction on the Serum Levels of the Cytokines: Interleukin-3 and Tumor Necrosis Factor 总被引:1,自引:0,他引:1
Background: Morbid obesity and malnutrition have both been demonstrated to have deleterious effects on the immune function.
Cytokines are immunomodulatory peptides that have profound effects on immune function. To the authors' knowledge, the effect
of surgically induced weight reduction on the cytokine levels has yet not been studied. In the present study, the authors
determined the effect of surgically induced weight reduction on the levels of the cytokines interleukin-3 (IL-3) and tumor
necrosis factor-α (TNF-α). Methods: 14 patients undergoing silicone ring vertical gastroplasty were included in the study
(mean BMI 48.85 kg/m2; range 38.1-52.0 kg/m2). Determination of the IL-3 and TNF-α levels was performed preoperatively and 14 days and 6 months postoperatively, when
all patients had lost 25% to 30% of their preoperative weight. Results: The IL-3 values before the procedure, and 14 days
and 6 months after, were as follows: 9.69 ± 1.82, 9.36 ± 1.28, and 8.42 ± 1.26 pg/mL, respectively (P < 0.05 preoperative versus 6 months postoperative level). The preoperative TNF-α levels showed a wide distribution. For this
reason, the patients were divided into two groups: Group A with preoperative values >10 pg/mL and Group B with values <10
pg/mL. In Group A, a significant decrease from the preoperative level of 24.46 ± 6.83 to 7.59 ± 4.56, and 6.69 ± 5.46 pg/mL
was measured at 14 days and 6 months postoperatively, respectively (P < 0.05). In Group B, the TNF- α levels were not significantly changed and were 5.45 ± 2.26, 7.59 ± 4.56, and 8.82 ± 6.27
pg/mL, respectively. Conclusion: The present study demonstrates a significant decrease in the levels of the cytokines, IL-3
and TNF-α. These changes can be responsible for alteration of the immune function after surgically induced weight reduction. 相似文献
4.
Constantine P. Spanos Panagiota Papaconstantinou Panagiotis Spanos Michael Karamouzis George Lekkas Christos Papaconstantinou 《Journal of gastrointestinal surgery》2007,11(3):247-255
Background Intestinal ischemia/reperfusion (I/R) results in local mucosal injury, systemic injuries, and organ dysfunction. These injuries
are characterized by altered microvascular and epithelial permeability and villous damage. Activation of neutrophils, platelets,
and endothelial factors are known to be involved in this process. Cytokines such as TNF-α, IL-1, IL-6, and oxygen-derived
free radicals are believed to be important pathogenic mediators. Capillary no-reflow is also known to play a role in I/R.
The aim of our study was to examine the role of l-arginine, a known nitric oxide (NO) donor, and aprotinin, a protease inhibitor with multiple effects, on intestinal I/R.
Methods Pigs weighing 20–25 kg were used. Ischemia was established by clamping the superior mesenteric artery (SMA) at its origin
and was sustained for 2 hours. Duration of reperfusion was 2 hours. The animals were divided into four groups: group A, the
control group, which was submitted to I/R injury only; group B, in which l-arginine was administered at a rate of 5 mg/kg/min during ischemia and continuing throughout reperfusion; group C, in which
aprotinin was administered with an initial bolus dose of 20,000 U/kg during ischemia followed by a continuous dose at 50 U/hour
throughout reperfusion; and group D in which both substances were administered. In all groups TNF-α, IL-1, and IL-6 levels
were measured using ELISA at baseline, 2 hours of ischemia, and 1 hour and 2 hours of reperfusion. SMA blood flow was measured
with a Doppler probe at baseline, 10 min, 1 hour, and 2 hours of reperfusion. Histological changes of the intestinal mucosa
were examined and graded on a five-point scale in all groups.
Results In the control group, levels of TNF-α, IL-1, and IL-6 were significantly increased during reperfusion (p < 0.05) compared to baseline. Administration of l-arginine and aprotinin led to suppression of the release of TNF-α, IL-1, and IL-6 during reperfusion in a statistically significant
manner (all p < 0.05). A synergistic or additive effect of l-arginine and aprotinin was not observed. SMA blood flow in the control group was decreased (p > 0.05) during reperfusion compared to baseline. In animals treated with l-arginine and aprotinin, SMA blood flow during reperfusion was significantly increased (p < 0.05) compared to the control group. Histologic examination of the intestinal mucosa was characterized by flattening of
the villi and necrosis in the control group. In the treated animals, less severe histological changes were noted.
Conclusions Administration of l-arginine and aprotinin may lead to amelioration of intestinal I/R injury. We did not note a synergistic or additive effect
of these two substances. These findings warrant further studies in clinical settings for future treatment efforts.
This paper was presented as a poster at the 47th Annual Meeting of the Society for Surgery of the Alimentary Tract, Los Angeles,
California, May 20–24, 2006. 相似文献
5.
O. Bernard-Poenaru C. Roux R. Blanque´ C. Gardner M. C. de Vernejoul M. E. Cohen-Solal 《Osteoporosis international》2001,12(9):769-776
Conflicting results have been reported in several cross-sectional studies measuring cytokine production from adherent monocytes
in pre- and postmenopausal women. Furthermore, the target cells for the action of estrogen are still debated. We therefore
assessed in a longitudinal manner the cytokine production from different fractions of peripheral blood mononuclear cells (PBMC)
cultured for 48 h. PBMC were obtained from 30 postmenopausal women before and after 6 months of hormone replacement therapy
(HRT). Women were randomly allocated to two groups: an adherent PBMC group (n= 20) and a total PBMC group (n= 9). After 6 months of treatment, urinary pyridinoline levels were markedly decreased in both groups (353 ± 24 vs 114 ± 13
μg/mmol creatinine and 325 ± 35 vs 164 ± 31 μg/mmol creatinine respectively, p<0.01). Culture supernatants were assayed for interleukin 1β (IL-1β), interleukin 6 (IL-6), soluble IL-6 receptor (IL-6rs)
and tumor necrosis factor alpha (TNF-α). In the adherent PBMC group, HRT induced a nonsignificant trend toward decreased levels
of IL-1β (35 ± 10 vs 13 ± 5 pg/ml), TNF-α (333 ± 58 vs 222 ± 30 pg/ml) and IL-6 (115 ± 70 vs 17 ± 10 pg/ml). In contrast,
in the total PBMC group, HRT induced a consistent and dramatic decrease in levels of IL-1β (104 ± 22 vs 25 ± 8 pg/ml), IL-6
(5950 ± 1041 vs 1011 ± 361 pg/ml), IL-6rs (148 ± 33 vs 35 ± 12 pg/ml) (p<0.01) and TNF-α (1468 ± 315 vs 585 ± 207 pg/ml, p= 0.05). We then evaluated whether HRT had the same effect in vitro. Adherent or total PBMC of 8 postmenopausal women were
cultured with or without 10−8M 17β-estradiol or tibolone for 48 h. Production of IL-1β, TNF-α, IL-6 and IL-6rs was not affected by the presence of 17β-estradiol
or tibolone in cultures of these cell fractions. In conclusion, our data indicate that non-adherent PBMC could mediate the
response to HRT. HRT may exert its action indirectly via noncirculating cells, as suggested by the absence of an in vitro
effect.
Received: 11 July 2000 / Accepted: 15 January 2001 相似文献
6.
At present, many investigations of myocardial function following ischemic insults concentrate on the modalities of reperfusion
rather than on the mode of preservation. In this study, we tried to define the effect of reperfusion using warm blood cardioplegia
(WBC) after medium-term (3 h) cold global ischemia, as required in cardiac transplantation. Twenty-one porcine hearts were
harvested after preservation with cold cardioplegia (St. Thomas Hospital solution) and topical cooling. Normothermic reperfusion
with blood was initiated after 3 h of ischemia utilizing a special extracorporeal pump circuit. Twelve hearts served as controls
(group A), while substrate-enriched WBC was applied during the initial 20 min of reperfusion in nine hearts (group B). Hearts
in both groups were then studied for myocardial function and metabolism under both working and nonworking conditions for a
maximum of 180 min. In the nonworking mode, left ventricular dp/dt was significantly higher in group B than in group A at
15 min (2201±785 mm Hg/sec vs 1515±732 mm Hg/sec) and at 180 min (1730±471 mm Hg/sec vs 836±147 mm Hg/sec;P<0.05). After 3 h, lactate production was significantly higher in group A (371±45 mg/dl) than in group B (108±44 mg/dl;P<0.05). Creatine kinase release into the coronary sinus was also significantly elevated in group A at 15 min (2807±1478 IU/l
vs 1148±1272 IU/l;P<0.05). Similarly, the hemodynamic data obtained under working conditions in group B were superior to those in group A. We
conclude that following 3 h of cold global ischemia, reperfusion with WBC improves myocardial function and metabolism. Cautious
application in clinical heart transplantation is recommended. 相似文献
7.
Background The present study was designed to elucidate the relationship of engraftment efficiency of transplanted cells and Kupffer cell
function in mice with acute on chronic liver injury and acute liver injury.
Methods The recipient dipeptidyl peptidase IV knockout (DPPIV–/–) mice were divided into two groups: (1) the acute on chronic liver injury group (CCl4/APAP group) that received CCl4 (1 ml/kg) twice a week for 4 weeks following one dose of acetaminophen (APAP), 600 mg/kg; (2) the acute liver injury group
(APAP-only group) that received a single dose of APAP at 600 mg/kg. DPPIV+/+ hepatocytes were transplanted 24 h after APAP intoxication. Engraftment efficiency was evaluated at day 7 and day 14 after
transplantation. The tumor necrosis factor-α (TNF-α) mRNA expression level of Kupffer cells immediately before cell transplantation
was compared between the two groups before and after lipopolysaccharide (LPS, 100 ng/ml) stimulation.
Results The number of transplanted cells and clusters in each 100× microscopic field were higher in the CCl4/APAP group at both day 7 (21.5 ± 6.3 versus 8.3 ± 4.0, p < 0.001; 14.9 ± 4.6 versus 6.6 ± 3.4, p < 0.001, respectively) and day 14 (17.3 ± 4.4 versus 10.2 ± 3.3, p = 0.001; 12.6 ± 3.2 versus 7.9 ± 1.6, p = 0.004, respectively). After LPS stimulation, the expression level of TNF-α was lower (175.7 ± 54.6 versus 465.6 ± 64.2,
p = 0.002), and the increment of TNF-α expression was also less significant in the CCl4/APAP group (1.5-fold versus 6.5-fold, p = 0.014).
Conclusions Chronic liver injury desensitized Kupffer cells and reduced TNF-α expression, two results that correlated with the increased
engraftment of transplanted cells. 相似文献
8.
Sabry A Elbasyouni SR Sheashaa HA Alhusseini AA Mahmoud K George SK Kaleek EA abo-Zena H Kalil AM Mohsen T Rahim MA El-samanody AZ 《International urology and nephrology》2006,38(3-4):731-737
Background Systemic lupus Erythematosus (SLE) is a rheumatic autoimmune disease characterized by multisystem organ involvement and by
high titers of auto antibodies against several nuclear and cytoplasmic antigens. Numerous abnormalities of the cytokine network
have been described in patients suffering from SLE. However the role of cytokines in different organ involvement is not yet
well defined.
Objective To determine if levels of Interlukin-6 (IL-6) and Tumor necrosis factor (TNF-α) correlate with SLE disease activity in Egyptian
SLE patients and more specifically with hematological involvement.
Methods Levels of TNF-α and IL-6 in serum samples from sixty individuals (40 with Systemic lupus Erythmatosus and 20 healthy controls)
were determined and renal biopsies were obtained from SLE patients.
Results Levels of TNF-α and IL-6 were higher in SLE patients with active compared with inactive hematological disease. Further analysis
showed that this association was dependent on inverse correlation (P=0.017, r=−0.49) for IL-6 and (P=0.76, r=−.243) for TNF-α. The mean level of TNF-α and Il-6 was (766.95±357.82 pg/ml) and (135.4±54.23 pg/ml) respectively for patients
with active disease while it was (314.01±100.87 pg/ml) and (47.33±18.61 pg/ml) for those with inactive disease and (172.7±39.19
pg/ml) and (21.15±10.99 pg/ml) for the healthy control group respectively. The difference was statistically significant (P=0.002). We found significant positive correlations between TNF-α and IL-6 and the SLE Disease Activity Index (SLEDAI) score.
(r=+0.743 and +0.772 respectively).
Conclusion Raised level of Il-6 and TNF-α may influence the development of anemia in Egyptian patients with Lupus Nephritis. 相似文献
9.
摘要:目的:探讨B7-1和B7-2在大鼠肝脏冷缺血再灌注损伤时的表达及其免疫学意义。方法:将30只大鼠随机分为3组:A组为假手术组(对照组);B组为冷缺血20min再灌注24h组;C组为冷缺血30min再灌注24h组。分别取各组之肝脏,采用实时反转录聚合酶链反应(RT-PCR)检测肝组织中B7-1和B7-2mRNA的表达。结果:B7-1mRNA在B,C组表达为0.529±0.089和0.618±0.074,均较A组(0.131±0.012)明显增高(P<0.01)。B7-2mRNA在B,C组表达为0.474±0.132和0.682±0.095,均较A组(0.163±0.054)明显增高(P<0.01)。并且B7-1和B7-2在C组表达明显高于B组(P<0.05)。结论:冷缺血再灌注时肝脏B7-1和B7-2表达上调,增加了肝脏的免疫原性。 相似文献
10.
Local liberation of cytokines during liver preservation 总被引:2,自引:0,他引:2
J. Gerlach Achim Jörres Roland Nohr Katrin Zeilinger Gabriele Spatkowski Peter Neuhaus 《Transplant international》1999,12(4):261-265
In order to investigate locally produced mediators during the process of organ storage in liver transplantation, we collected
the liver preservation solution effluent of 15 transplanted livers and compared it with serum samples taken preoperatively
from donor and recipient, as well as 60 min after reperfusion. The mean ischemia time ± SEM was 10 h 10 min ± 53 min. Mean
concentrations in University of Wisconsin preservation solution effluent were: interleukin-(IL-)1β 154 ± 77 pg/ml; IL-1 receptor antagonist (IL-1 ra) 1281 ± 309 pg/ml; IL-6 412 ± 90 pg/ml; and for tumor necrosis factor-(TNF-)α
74 ± 21 pg/ml. Cytokine levels in the donors were lower than those detected in the effluent. All measured cytokines showed
higher concentrations in the effluent compared to those of the recipient prior to the operation. With respect to a comparison
of donor and recipient values, no correlation is evident. Likewise, the ischemic time does not correlate with effluent values.
Further development of liver preservation concepts requires information about the state of the graft before reperfusion. Data
on cytokine liberation may serve as a helpful tool for the further development of preservation concepts because they enable
an estimation of cell activation during preservation.
Received: 2 June 1997 Accepted: 10 November 1998 相似文献
11.
Background Laparoscopic and open preperitoneal hernia repair techniques both use the preperitoneal space. This study investigated whether
the surgical approach to the inguinal canal affects outcome measures.
Methods One hundred sixty patients with inguinal hernia were assigned randomly into open anterior (42), open preperitoneal (39), laparoscopic
transabdominal preperitoneal (39), and laparoscopic total extraperitoneal (40) groups according to the surgical method. The
peroperative serum tumor necrosis factor-α (TNF-α) levels, interleukin-6 (IL-6) levels, VAS scores at 6 and 48 h, per- and
postoperative complications, and recurrence rates were determined as main variables.
Results The serum IL-6 levels were 335 ± 1.8, 283 ± 1.8, 283 ± 1.4, and 269.3 ± 1.6 pg/ml in the open anterior, posterior, transabdominal
preperitoneal, and total extraperitoneal groups, respectively (P < 0.01). The TNF-α levels were highest in the open anterior group. The pain scores were lower in groups undergoing the posterior
approach than in the open anterior approach group.
Conclusion The approach to the inguinal canal through the preperitoneal space appears to be less invasive than the transinguinal anterior
approach. 相似文献
12.
Flávia Mafra de Lima Jan M. Bjordal Regiane Albertini Fábio V. Santos Flavio Aimbire 《Lasers in medical science》2010,25(5):661-668
Low-level laser therapy (LLLT) has been found to produce anti-inflammatory effects in a variety of disorders. Bronchial smooth
muscle (BSM) hyperreactivity is associated with increased Ca+2 sensitivity and increased RhoA mRNA expression. In the current study, we investigated if LLLT could reduce BSM contraction
force and RhoA mRNA expression in tumor necrosis factor-α (TNF-α)-induced BSM hyperreactivity. In the study, 112 male Wistar
rats were divided randomly into 16 groups, and BSM was harvested and suspended in TNF-α baths for 6 and 24 h, respectively.
Irradiation with LLLT was performed with a wavelength of 660 nm for 42 s with a dose of 1.3 J/cm2. This LLLT dose was administered once in the 6-h group and twice in the 24-h group. LLLT significantly decreased contraction
force in BSM at 6 h (TNF-α + LLLT: 11.65 ± 1.10 g/100 mg of tissue) (F = 3115) and at 24 h (TNF-α + LLLT: 14.15 ± 1.1 g/100 mg of tissue) (F = 3245, p < 0.05) after TNF-α, respectively, when compared to vehicle-bathed groups (control). LLLT also significantly decreased the
expression of RhoA mRNA in BSM segments at 6 h (1.22 ± 0.20) (F = 2820, p < 0.05) and 24 h (2.13 ± 0.20) (F = 3324, p < 0.05) when compared to BSM segments incubated with TNF-α without LLLT irradiation. We conclude that LLLT administered with
this protocol, reduces RhoA mRNA expression and BSM contraction force in TNF-α-induced BSM hyperreactivity. 相似文献
13.
Robinson Joannides Isabelle Etienne Michele Iacob Bruno Hurault De Ligny Stephane Barbier Jeremy Bellien Yvon Lebranchu Christian Thuillez Michel Godin 《Transplant international》2010,23(11):1135-1143
This study attempted to establish whether a calcineurin inhibitor (CNI)‐free immunosuppressant regimen based on sirolimus (SRL) is associated with a preservation of conduit arteries endothelial function in kidney recipients or not. Twenty‐nine kidney recipients were randomized to receive since transplantation SRL (n = 15) or cyclosporin A (CsA, n = 14) associated with mycophenolate mofetil (MMF) and steroids (6 months) in a parallel prospective study. Systolic, diastolic blood pressures, glomerular filtration rate (GFR) and radial artery flow‐mediated dilatation (FMD) induced by postischaemic hyperaemia were assessed in a blind manner at one (M1) and 7 months (M7) after transplantation. Endothelium‐independent dilatation was assessed by glyceryl trinitrate spray. There was no difference between the groups for all vascular parameters at M1. At M7, systolic blood pressure was lower (SRL: 119 ± 3 vs. CsA: 138 ± 4 mmHg, P < 0.05) and FMD was higher in SRL compared with CsA (SRL: 13.1 ± 0.9 vs. CsA: 9.9 ± 0.9%, P < 0.05) without any difference for hyperaemia, endothelium‐independent dilatation and GFR (SRL: 66.7 ± 1.05 vs. CsA: 67.5 ± 1.22 ml/min). Our results demonstrate that a CNI‐free regimen based on SRL and MMF prevents conduit artery endothelial dysfunction compared with CsA and MMF in kidney recipients suggesting a beneficial arterial wall effect that may also contribute to the decrease in systolic blood pressure. 相似文献
14.
B. Hausen Markus Bahra Peter Mueller Christian F. Poets Charles W. Hewitt Randall E. Morris 《Transplant international》1998,11(3):186-194
Based on the known properties of ambroxol and dexamethasone to inhibit inflammation and increase endogenous surfactant levels,
the potential advantage of donor pretreatment with either drug was investigated in an acute rat double-lung transplant model.
Donor animals were randomly assigned to one of three treatment groups: an ambroxol group (AMB; 0.4 mg/kg), a dexamethasone
group (DX; 2 mg/kg); or an untreated control group (CN). Drugs were given intraperitoneally 6 h prior to harvest. Following
standard preservation and 16 h of cold ischemia, the donor double lung block was implanted into syngeneic recipients using
custom-designed stents for the vascular anastomosis. During reperfusion, serial measurements of graft pulmonary vascular resistance
and alveolar-arterial oxygen difference were obtained. Separate graft ventilation allowed determination of graft dynamic lung
compliance. Final assessment included weight gain and histology. For phospholipid analysis, lung lavages were performed in
the three study groups at the end of reperfusion and compared to levels before graft harvest. Donor pretreatment did not significantly
affect preharvest phospholipid levels. Survival following graft ischemia and reperfusion was shortest after AMB (92 ± 5 min)
and longest after DX (110 ± 5 min; DX vs AMB P < 0.03) and CN (116 ± 4 min; CN vs AMB P < 0.02). DX pretreatment provided better compliance (P < 0.02) and lower vascular resistance (P < 0.0001) than AMB treatment. Airway resistance was lower in the AMB and DX groups than in controls (P < 0.04 and P < 0.02, respectively). The alveolar-arterial oxygen difference was markedly similar in all groups. Graft weight gain amounted
to 114 % ± 10 % in AMB, 88 % ± 12 % in DX, and 98 % ± 13 % in CN (P = NS). Thus, in this rat lung transplantation model, donor pretreatment with dexamethasone did not improve graft function
compared to untreated controls and donor pretreatment with ambroxol was found to be potentially detrimental to graft function
during reperfusion.
Received: 5 September 1997 Received after revision: 28 November 1997 Accepted: 14 January 1998 相似文献
15.
Fernando Lopez-Neblina Alexander H. Toledo Luis H. Toledo-Pereyra 《Journal of investigative surgery》2013,26(4):257-263
We developed an improved solution for hypothermic storage (0–4°C) of kidneys. The cold storage solution (HBS) was composed of macromolecules, high-energy cellular substrates, and a mixture of antiproteolytic amino acids, antioxidants, and anti-inflammatory compounds. The objectives in developing this solution were to achieve superior metabolic support of the kidney during cold storage and to protect against ischemic injury. Inbred Brown Norway rats, weighing 225–250 g, were subjected to orthotopic ultrarapid technique for kidney isotransplantation to minimize warm ischemia and to test the preservation process. The kidney was transplanted after 12 h of preservation. The animals were divided into three groups based upon the preservation solution utilized: HBS solution, HTK solution (Custodiol), and UW solution (UWS)(ViaSpan). Among the recipients, each group had two subsets. The first subset of animals was used to assess survival at 7 days as well as the reperfusion damage index (RDI) based on the macroscopic physical characteristics of the kidney at the time of transplantation. The second subset in each group was utilized to measure serum creatinine and blood urea nitrogen at 4 and 7 days, and histology at death or sacrifice. Mean ± standard deviation (M ± SD) was used for all parameters studied. The HBS solution showed significantly better protection at 12 h when compared to HTK and UW solutions. The reperfusion damage index (RDI) showed excellent preservation in the HBS (14 ± 1), good preservation in UWS (13 ± 1.5), and moderate preservation in the HTK (11 ± 2) group. Histology was in concordance with the RDI, showing better histological findings with HBS and UW solutions than with the HTK group. Serum creatinine was significantly better in the HBS group when compared to HTK and UWS. Survival was statistically different, with 80% survival at 7 days in the HBS group, 20% survival in the HTK group, and 50% survival in the UWS group (p <. 05). The HBS solution offered a new alternative for kidney cold storage with significantly better results when compared to the current gold standards of HTK and UW solutions in Brown Norway rats. This solution warrants further testing in other mammals. 相似文献
16.
Spolidorio LC Nassar PO Nassar CA Spolidorio DM Muscará MN 《Calcified tissue international》2007,81(2):114-123
Tacrolimus is used for transplant patients with refractory graft rejection and those with intolerance to cyclosporin (CsA),
without the disfiguring adverse effects frequently attributed to CsA therapy. Since we have shown that CsA-associated bone
loss can also affect alveolar bone, the purpose of this study was to evaluate the effects of conversion of monotherapy from
CsA to tacrolimus on alveolar bone loss in rats. Groups of rats were treated with either CsA (10 mg/kg/day, s.c.), tacrolimus
(1 mg/kg/day, s.c.), or drug vehicle for 60 and 120 days, and an additional group received CsA for 60 days followed by conversion
to tacrolimus for a further 60-day period. Bone-specific alkaline phosphatase (BALP), tartrate-resistent acid phosphatase
(TRAP-5b), calcium (Ca2+), interleukin (IL)-1β, IL-6, and tumor necrosis factor α (TNF-α) concentrations were evaluated in the serum. Analyses of
bone volume, bone surface, number of osteblasts, and osteoclasts were performed. Treatment with CsA for either 60 or 120 days
was associated with bone resorption, represented by lower bone volume and increased number of osteoclasts; serum BALP, TRAP-5b,
IL-1β, IL-6, and TNF-α were also higher in these animals. After conversion from CsA to tacrolimus, all the altered serum markers
returned to control values in addition to a significant increase of bone volume and a lower number of osteoclasts. This study
shows that conversion from CsA to tacrolimus therapy leads to a reversal of the CsA-induced bone loss, which can probably
be mediated by downregulation of IL-1β, IL-6, and TNF-α production. 相似文献
17.
Sean C. Glasgow M.D. Sathyabama Kanakasabai M.D. Sabarinathan Ramachandran Ph.D. T. Mohanakumar Ph.D. William C. Chapman M.D. 《Journal of gastrointestinal surgery》2006,10(3):357-364
Hepatic cryoablation can produce acute lung injury, with activation of nuclear factor (NF)-кB in the remnant liver and lungs,
production of C-X-C chemokines, and neutrophil infiltration of the lungs. Ac-tivated complement stimulates NF-к B and cytokine
secretion from Kupffer cells. The role of comple-ment in the development of acute lung injury after cryoablation was examined
using HLL transgenic mice (5’ HIV-LTR-Luciferase gene; 5’ HIV-LTR is an NF-к B-dependent promoter). Total comple-ment depletion was achieved with preoperative administration
of cobra venom factor (CVF). After he-patic cryoablation, bioluminescent NF-кB activity increased in the nonablated liver
remnant by 4 hours in both control (119,093 ± 22,808 net RLU/mg protein) and CVF-treated mice (117,722 ± 14,932) from cumulative
baseline (657 ± 90, P < 0.0001). In the lung, complement-depletion induced significantly greater increases in NF-к B activation at both early and
later times. Likewise, chemokines were higher in complement-depleted mice relative to controls (KC: 493 ± 43 versus 269 ±
29 pg/mg protein, P < 0.001; MIP-2: 171 6 29 versus 64 6 13 pg/mg protein, P < 0.0001). Pulmonary myelo-peroxidase activity was equivalent at 24 hours, but complement-depletion caused a significantly
more rapid influx of neutrophils. Complement depletion results in increased pulmonary inflammation follow-ing liver cryo injury
via relative upregulation of NF-к B activity. Activated complement is not the initiator of the systemic inflammatory response;
in fact, downstream components of the complement cascade may diminish subsequent inflammation.
Presented at the Forty-Sixth Annual Meeting of The Society for Surgery of the Alimentary Tract, May 14–18, 2005, Chicago,
Illinois. 相似文献
18.
Streptozotocin administration in newborn rats (nSTZ-rats) leads to adults with mild insulin deficiency and normoglycemia,
and is accepted as a model of type 2 diabetes. We examined possible differences in the production of inflammatory mediators
between healthy and nSTZ-rats after ischemia-reperfusion (I-R). Two-month-old control and nSTZ-rats were randomly separated
into control and intestinal I-R groups. After reperfusion, samples were obtained from the portal vein (PV) infrahepatic cava
vein (ICV), suprahepatic cava vein (SCV), jejunal wall, and pancreas. Nitric oxide (NO), lipid hydroperoxides (LPO), tumor
necrosis factor alpha (TNF-α), 60 kDa receptor (sTNF-R1), 80 kDa (sTNF-R2), and intercellular adhesion molecule-1 (ICAM-1),
were determined. After I-R, nSTZ-rats showed increased plasma concentrations of LPO, NO, ICAM-1 (0.5141 ± 0.083 vs 0.024 ±
0.003, ICV; 0.574 ± 0.075 vs 0.023 ± 0.003, SCV; 0.528 ± 0.067 vs 0.027 ± 0.003 PV; ng/ml), TNF-α (42.4 ± 5.7 ICV, 248.4 ± 28.2 SCV, and 33.6 ± 4.0 PV. In n STZ-rats, vs 4.36 ± 0.57, 4.74 ± 0.77, and 3.16 ± 0.32, respectively,
in control rats; pg/ml), and sTNF-R1. Both TNF-α and NO plasma levels were higher in SCV than in ICV and PV after I-R. In
addition, after I-R, jejunal wall of nSTZ-rats showed an increase of TNF-α IL-1, and IL-10 levels. A pre-existing state of
glucose intolerance intensifies the inflammatory response after intestinal I-R. 相似文献
19.
Tumor Necrosis Factor-α, Interleukin-1β and Nitric Oxide: Induction of Liver Megamitochondria in Prehepatic Portal Hypertensive Rats 总被引:2,自引:0,他引:2
Prieto I Jiménez F Aller MA Nava MP Vara E Garcia C Arias J 《World journal of surgery》2005,29(7):903-908
Abstact It has been shown that portal hypertension in the rat causes microvesicular hepatocytic fatty infiltration. Formation of megamitochondria
(MG) is one of the most prominent alterations in steatosis. Because nitric oxide (NO), tumor necrosis factor-α (TNFα), and
interleukin-1β (IL-1β) impair mitochondrial function, these mediators have been studied in prehepatic portal hypertensive
rats to verify their coexistence with MG and therefore with steatosis. Male Wistar rats were divided into two groups: a control
group (n = 7) and a group with partial portal vein hgation (n = 19) at 6 weeks of evolution. TNFα and IL-1β were quantified in liver by enzyme-linked immunosorbent assay, and NO was measured
in the portal vein, suprahepatic inferior vena cava, and infrahepatic inferior vena cava by the Griess reaction. In portal
hypertensive rats, the-serum concentration of NO of hepatic origin increases (132.10 ± 34.72 vs. 52.44 ± 11.32 nmol/ml; p < 0.001), as do TNF-α (2.02 ± 0.20 vs. 1.12 ± 0.43 μmol/mg protein) and IL-1β (18.95 ± 2.59 vs. 5.48 ± 1.70 μmol/mg protein)
(p = 0.005) in the liver. The most frequent hepatic histologic findings are the presence of MG (p < 0.001), steatosis, and hyperplasia. An increase in hepatic release of NO, TNFα and IL-Iβ with MG formation is produced
in rats with portal hypertension. Therefore these proinflammatory mediators and this morphologic mitochondrial alteration
could both be involved in the etiopathogenesis of steatosis. 相似文献
20.
Molina A Vendrell J Gutiérrez C Simón I Masdevall C Soler J Gómez JM 《Obesity surgery》2003,13(4):615-621
Obesity is a complex disease associated with insulin resistance. Leptin and the TNF-α system could be involved in the pathogenesis
of obesity and insulin resistance. Gastric bypass (GBP) is a surgical treatment for morbidly obese patients. We conducted
a study after GBP to analyze the pattern of variation of anthropometric and body composition variables, leptin and sTNFR1
and 2. Methods: 29 morbidly obese women were studied, at baseline and throughout 6 months after gastric bypass. Results: At
baseline, the BMI was 49 ± 6 kg/m2 and patients showed a higher fasting insulin resistance index (FIRI), leptin, leptin/fat mass and sTNFR1 and 2 than did controls.
6 months after GBP, BMI was 35±4, and FIRI, leptin and leptin/fat mass decreased significantly in the first months and throughout
the follow-up. sTNFR1 and 2 showed an initial increase, but at 6 months their concentrations were similar to baseline (2.6±0.8
vs 3.1±0.95 ng/ml, P < 0.05; 4.6±1.4 vs 7±2.5 ng/ml, P < 0.05). At baseline, there was no correlation between leptin and BMI and body composition variables but there was a correlation
with fat mass (r=0.42, P=0.004) and sTNFR1 (r=0.58, P=0.001). At 6 months, there was a correlation between leptin and BMI (r=0.53, P=0.004) and sTNFR1 (r=0.46, P=0.013). Conclusions: Morbidly obese women after GBP became less insulin resistant with lower leptin concentrations, but showed
an initial increase of sTNFR1 and 2. This pattern of variation of the leptin TNF-α axis suggests a disregulation of the system
after dramatic weight loss and also that insulin and leptin up-regulate TNF-α production irrespective of insulin resistance
status. 相似文献