[Correlation analysis between prenatal exposure of per-/polyfluoroalkyl compounds and neonatal outcome].

Objective: To investigate the correlation between the prenatal exposure of per-/polyfluoroalkyl substances (PFASs) and the neonatal outcome. Methods: A total of 506 maternal infant cohort samples were collected in Hangzhou, Zhejiang province from 2020 to 2021. The exposure levels of seven PFASs in maternal serum before delivery were detected by solid-phase extraction-ultra performance liquid chromatography tandem mass spectrometry. Multivariable linear regression model was used to analyze the influence of prenatal exposure of PFASs on birth weight, birth length and Apgar score. Results: The maternal age, prenatal body mass index and gestation age were (31.3±4.3) years old, (26.7±3.2) kg/m2 and (265.0±28.3) days, respectively. The birth weight, birth length and scores of Apgar-1 and Apgar-5 were (3.1±0.8) kg, (49.3±2.9) cm, (9.88±0.47) points and (9.99±0.13) points, respectively. PFASs were widely distributed in maternal serum, with the highest concentration of (18.453±19.557) ng/ml, (6.756±9.379) ng/ml and (5.057±8.555) ng/ml for perfluorooctanoic acid (PFOA), perfluorooctane sulfonate (PFOS) and 6∶2 chlorinated polyfluorinated ether sulfonate (Cl-PFESA), respectively. Maternal age, parity and delivery mode were associated with the exposure level of PFASs (P<0.05). Subgroup analysis showed that PFOS had negative effects on birth weight (ß=-0.958), birth length (ß=-0.073) and Apgar-5 score (ß=-0.288) for neonates in the low birth weight (LBW) group. 6∶2 Cl-PFESA and 8∶2 Cl-PFESA inhibited the birth weight (ß=-0.926; ß=-0.552) and length (ß=-0.074; ß=-0.045) of newborn in the LBW group. In addition, 4∶2 fluorotelomer sulfonate (FTS) was associated with increased birth weight (ß=0.111) and decreased Apgar-5 score (ß=-0.030) in the normal weight group. Conclusion: Prenatal exposure to PFASs is associated with birth weight, birth length and Apgar-5 score. It is necessary to continue to pay attention to the impact of PFASs on fetal growth and development through maternal-fetal transmission.

[Resting-state functional magnetic resonance imaging analysis of modified electroconvulsive therapy in the treatment of major depressive disorder].

Objective: To explore the effect of modified electroconvulsive therapy (MECT) on resting-state functional connectivity (RSFC) in patients with major depressive disorder (MDD). Methods: Patients with MDD from Anhui Mental Health Center from October 2017 to May 2019 were included. Using bilateral nucleus accumbens (NAcc) as seed points, changes of RSFC were investigated before and after MECT through resting-state functional magnetic imaging (fMRI). Antidepressant effects were measured by 17 items of Hamilton Depressive Rating Scale (HDRS-17). Correlation analysis was performed between changed HRSD-17 scores and changes of functional connectivity. Results: A total of 40 MDD patients (10 males and 30 females), aged (38±11) years, who received MECT were included in the study. After MECT, patients showed increased RSFC in the right NAcc (rNAcc) and superior frontal gyrus (P<0.001), right supramarginal gyrus (P<0.001), right angular gyrus (rAG) (P= 0.017), right inferior parietal lobule (P= 0.017), left superior frontal gyrus (LSFG) (P<0.001), left middle temporal gyrus (P=0.017) and left angular gyrus (LAG) (P=0.012), respectively. The RSFC changes of rNAcc-LSFG (r=-0.454, P = 0.003), rNAcc-rAG (r=-0.437, P=0.005) and rNAcc-lAG (r=-0.383, P=0.015) were negatively correlated with the changes of HRSD-17 scores. Conclusions: MECT may alleviate major depression by regulating the functional connectivity between the rNAcc and bilateral angular gyrus and left superior frontal gyrus.

[Clinical characteristics of "classical" and "non-classical" paraneoplastic neurological syndrome].

Objective: To explore the clinical features of classical and non-classical paraneoplastic neurological syndrome (PNS). Methods: From 2015 to 2020, 48 cases of definite PNS admitted to the First Affiliated Hospital of University of Science and Technology of China were retrospectively collected, and classification, clinical characteristics, onconeural antibodies and primary tumors were analyzed. The included cases were divided into classical and non-classical groups according to Graus criteria, and the differences of clinical characteristics, onconeural antibodies, combined tumors, time of diagnosis and mortality were compared between the two groups. Results: Among the 48 confirmed patients, 21 (43.8%) were positive for well-characterized onconeural antibodies. There were 28 cases (58.3%) and 20 cases (41.7%) in classic and non-classical PNS groups, respectively. No significant differences of age, sex, clinical involvement site, characteristic positive antibody type, tumor diagnosis rate and follow-up mortality were found between the two groups (all P>0.05). The time of diagnosis in the non-classical PNS group was 3.0 (2.0, 6.5) months, which was significantly longer than that in the classical PNS group 1.0(0.6, 3.0) months (P<0.05). Meanwhile, the combination rate of non-characteristic antibodies in the classical PNS group (10 cases, 35.7%) was significantly higher than that in the non-classical PNS group (1 case, 5.0%) (P=0.016). During the follow-up, 39 patients (81.3%) with tumor were confirmed, and 29 patients (60.4%) were diagnosed with PNS before the tumor was found. Conclusions: The"non-classical"PNSs are common in clinical settings. Diagnosis may be delayed due to the nonclassical symptoms of the patients. When patients have clinical symptoms related to PNS, onconeural antibodies should be detected and the relevant tumors should also be screened. Patients have positive antibodies but with no tumors should be closely followed up for more than 5 years.

[Cognitive function and cerebral blood perfusion changes in patients with anti-N-methyl-D-aspartate receptor encephalitis].

Objective: To investigated cognitive and cerebral blood flow changes in a cohort of patients with anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis. Methods: Fifteen patients with confirmed anti-NMDAR encephalitis from the First Affiliated Hospital of Anhui Medical University and the First Affiliated Hospital of University of Science and Technology of China between June 2015 and February 2019 were included in the study. Meanwhile, another 15 healthy subjects were selected as controls. All participants underwent neuropsychological tests for assessment of the clinical symptoms and arterial spin labeling (ASL) of magnetic resonance perfusion imaging scan were employed to evaluate cerebral perfusion. Then the relationship between changed cerebral blood perfusion and cognitive function was evaluated. Results: Patients with anti-NMDAR encephalitis showed significantly reduced overall cognitive function (Montreal cognitive assessment (MoCA)) than healthy controls (26.5±2.5 vs 28.6±1.9, P=0.015), they also exhibited poorer performance in immediate memory, recognition, attention, language and executive function than healthy controls (P<0.05). However, no significant differences in clinical symptoms, viability, mental state and mood were observed between the two groups (P>0.05). Patients with anti-NMDAR encephalitis showed significantly reduced total brain cerebral blood flow (CBF) compared with the healthy controls (0.949±0.028 vs 0.953±0.025, P=0.001). Compared with the healthy controls, the patients had decreased CBF in triangular and opercular parts of bilateral inferior frontal gyrus and left central frontal gyrus, however, they showed increased CBF in the left inferior temporal gyrus and left fusiform gyrus (all P<0.05). In NMDAR group, the CBF in left central anterior gyrus was negatively correlated with Stroop's Color Word-word (r=-0.68, P=0.005). The CBF in left spindle gyrus was positively correlated with Stroop's Color Word-word (r=0.62, P=0.015) and completion time of color trail test-A (r=0.81, P<0.001), respectively, however, it was negatively correlated with Chinese Auditory Verbal Learning Test-immediate (r=-0.59, P=0.020) and Verbal Fluency Test-animals (r=-0.58, P=0.024), respectively. Conclusions: Patients with anti-NMDAR encephalitis have prevalent cognitive deficits such as memory, language, attention and executive dysfunction as well as changes in blood perfusion, which may be related to cognitive deficits. Changes in cerebral blood perfusion can be used as indicators for early diagnosis, disease monitoring and prognosis evaluation of anti-NMDAR encephalitis. Improving the cerebral blood flow of patients may promote the recovery of cognition.

[Relationship between glycemic control and visceral adiposity index among the patients with type 2 diabetes mellitus].

OBJECTIVE: To explore the relationship between glycemic control and visceral adiposity index (VAI) among type 2 diabetes mellitus (T2DM) patients. METHODS: A community-based epidemiological field study for patients with T2DM aged ≥ 40 years was conducted in China.Every participant underwent physical examinations, biochemical tests of fasting glucose, glycosylated hemoglobin (HbA1c), total cholesterol (TC), triglyceride (TG), high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C) and so on, and a questionnaire, including anthropometric characteristics, lifestyle, disease history, family history, and medication use. Those participants with HbA1c ≥7.0% were classified as the poorly controlled in our analysis of relationship between glycemic control and VAI. Anthropometric characteristics, lifestyle, and biochemical indexes of the participants were compared among the groups of different VAI levels. Logistic models were applied in multiple analysis adjusting for possible confounders. RESULTS: A total of 1 607 patients with T2DM were recruited in our analysis with a mean age of (59.4±8.1) years and an average T2DM duration of (7.0±6.4) years. Among them, 78.3% were on hypoglycemic therapy. The cutoff points of quartiles of VAI were calculated for the males and females, respectively. According to the ascending order of the quartiles of VAI, the participants were divided into four groups, i.e. Q1, Q2, Q3, and Q4. The poor glycemic control rate for these groups were 60.6%, 65.7%, 70.1%, and 71.0%, respectively (Trend χ2=12.20, P<0.001). After adjustment for age, gender, systolic blood pressure (SBP), diastolic blood pressure (DBP), LDL-C, smoking, cardio-cerebral vascular disease (CVD) history, hypoglycemic therapy, T2DM duration, and family history of diabetes, the Logistic regression models showed that the glycemic control rate was significantly associated with VAI levels among the patients with T2DM. Compared with the participants in group Q1, the ORs of poor glycemic control for those in groups Q2, Q3, and Q4 were 1.239 (95%CI 0.918 to 1.672), 1.513 (95%CI 1.117 to 2.050), and 1.535 (95%CI 1.128 to 2.088), respectively (trend P=0.003). With each quartile increase in VAI, the OR of poor glycemic control was 1.162 (95%CI 1.054 to 1.282). CONCLUSION: The glycemic control among the patients with T2DM is significantly associated with VAI. High level of VAI is an indicator of poor glycemic control.

Isolating and confirming the Mudr­inserted flanking sequences of maize.

MuDR exhibits the highest transposition activity and insertional mutagenesis frequency in Mutator (Mu) family. If we isolate the MuDR­insertion­specific flanking sequences (MuDRFs), it will be crucial for using Mu element­mediated mutants. The MuDR­TAIL­PCR system was constructed and optimized using a combination of MuDR­TIR­nested specific primers and 12 arbitrary degenerate (AD) primers, modified reaction system and procedure and mutant DNA templates of 87 genotypes from M2 or M2:3 families created by crossing the W22::Mu line (active MuDR donor parent) from the UniformMu population with the Zong31 (Z31) line (recipient parent). Here 129 different MuDRFs were acquired by MuDR­TAIL­PCR, accounting for 86.60 % of the total mutant­specific agarose gel bands. In addition, we confirmed the authenticity of the non­redundant flanking sequence amplifications. The amplified non­redundant flanking sequences accounted for 65.12 % of the total MuDRFs, and 88.00 % of the non­redundant MuDRFs were inserted inside the genes. These results show that the MuDR­TAIL­PCR system that we developed can be used for specifically isolating MuDRFs.

Prognostic model for survival of local recurrent nasopharyngeal carcinoma with intensity-modulated radiotherapy.

BACKGROUND: Intensity-modulated radiotherapy (IMRT) is the main salvage treatment for advanced locally recurrent nasopharyngeal carcinoma (NPC); however, survival outcomes vary. We aimed to construct a prognostic-score model to identify patients who could benefit from salvage IMRT. METHODS: This retrospective study involved 251 patients with locally recurrent NPC. The following parameters were analysed following IMRT: patient performance status, age, gender, late complications, T-stage of recurrence, synchronous nodal recurrence, primary gross tumour volume (GTV-nx), disease-free interval, re-irradiation dose and chemotherapy. The model was based on the hazard ratio coefficients of six significantly negative prognostic factors for survival. RESULTS: Significantly negative prognostic factors included Karnofsky Performance Status ≤70, age >50 years, late complications, recurrent T(3-4) stage, synchronous nodal recurrence and GTV-nx >30 cm(3). Three subgroups were defined according to model scores: low risk (0-4), intermediate risk (5-8) and high risk (9-15). The 5-year overall survival rates were 64.3%, 32.2% and 7.7%, respectively. The main cause of death was radiation-induced complications. CONCLUSION: The prognostic-score model demonstrated that re-irradiation with IMRT is suitable for low-risk and intermediate-risk patients but may be unsuitable for high-risk patients. Further research into the protection of critical adjacent organs to reduce late complications in these patients is warranted.

Distinct effects of antihypertensives on depression in the real-world setting: A retrospective cohort study.

BACKGROUND: Evidence is increasing that pathways of antihypertensives may have a role in the pathogenesis of depression. However, how the class of antihypertensives affects depression risk remains unclear. METHODS: The effects of different classes of antihypertensives on depression were explored using an insurance database in Beijing, China. Antihypertensives in our study included calcium channel blockers (CCBs), angiotensin-converting enzyme inhibitors (ACEIs), angiotensin II receptor blockers (ARBs), beta-blockers (BBs), and diuretics (DIUs). Those initially treated with only one class of antihypertensives were included. Stratified analysis was conducted for demographic characteristics, comorbidities, and statin prescriptions. RESULTS: In total, 181,709 newly detected hypertension patients were included. The median follow-up period was 4.33 years and 19,030 participants were with depression by the end. After adjusting for covariates, the incidence density (95% confidence interval, CI) of depression in the BB, ACEI, DIU, CCB, and ARB groups was 3.16 (2.98-3.33), 3.10 (2.91-3.29), 2.70 (2.45-2.94), 2.67 (2.53-2.81), and 2.30 (2.16-2.43) per 100 person-years, respectively. Compared with ARB group, the hazard ratio (95% CI) of depression for BB, ACEI, DIU, and CCB group was 1.37 (1.32-1.43), 1.35 (1.28-1.42), 1.17 (1.08-1.27), and 1.16 (1.12-1.21), respectively. Stratified analysis suggested the highest depression ID remained within the BB or ACEI group. LIMITATIONS: Detailed clinical information was unavailable, which may introduce bias. Patients on monotherapy as initial treatment were included and caution is needed for extrapolation. CONCLUSIONS: Compared with ARBs, there may be a class effect of other antihypertensives on the risk of depression.

Blockade of M1 muscarinic acetylcholine receptors modulates the methamphetamine-induced psychomotor stimulant effect.

Muscarinic acetylcholine receptors (M1-M5) regulate many key functions of the CNS and peripheral nervous system. In the present study, the role of M1 muscarinic receptors (M1R) in the psychomotor stimulant and sensitizing properties of methamphetamine (METH) is investigated using molecular, neurochemical, and behavioral approaches. Acute and repeated treatment with METH increased M1R mRNA expression in the frontal cortex and the CA2 region of the hippocampus. Repeated treatment with METH also increased M1R mRNA expression in the dentate gyrus. Dicyclomine, an M1R antagonist, did not affect the psychomotor effect of METH, but it attenuated METH-induced increases in the dopamine (DA) efflux in the nucleus accumbens (NAc). Dicyclomine enhanced the psychomotor effect of METH after repeated treatment with METH and 8.0 mg/kg of dicyclomine, and also augmented the increase in the NAc DA overflow evoked by repeated METH treatment. These results suggest that M1R plays a role in the METH-induced psychomotor stimulant effect by changing the release of DA in the NAc of mice.

[A Meta-analysis on the relations between short-term exposure to PM(2.5) and both mortality and related emergency visits in China].

Objective: To carry out a quantitative estimate that related to the effects of short-term exposure to PM(2.5) on all-cause mortality and emergency visits in China by using the systematic review and Meta-analysis. Methods: We selected all the studies published before March 2018 from China National Knowledge Infrastructure, Wanfang database, PubMed and EMBASE and data on relative risk (RR), excess risk (ER) and their 95%CIs: appeared in these papers were extracted. According to the differences in the size or direction (heterogeneity) of the results, we computed summary estimates of the effect values using a random-effect or fixed effect model. We also conducted the subgroup analysis and Meta-analysis to have assessed the selected studies for the evidence of study bias. Results: A total of 33 original studies, indexed in databases, were identified. Among those studies, 39 sets of data on mortality and 4 sets of data on emergency were valid to show that within the daily concentration range from 47.7 to 176.7 µg/m(3), for 10 µg/m(3) increases in PM(2.5) concentrations, it would increase the daily numbers of deaths by 0.49% (95%CI: 0.39%-0.59%) and 0.30% (95%CI: 0.10%-0.51%) for all-cause deaths and all-cause emergency-room visits, respectively. For subgroup analysis, the combined effect of PM(2.5) in causing short-term all-cause deaths in the northern areas (ER=0.42%, 95%CI: 0.30%-0.54%) seemed lower than that in the southern areas (ER=0.63%, 95%CI: 0.44%-0.82%). The combined effect of PM(2.5) concentration below 75 µg/m(3) (ER=0.50%, 95%CI: 0.37%-0.62%) was higher than that of PM(2.5) concentration ≥75 µg/m(3) (ER=0.39%, 95%CI: 0.26%-0.52%). Conclusion: Within the concentration range from 47.7 to 176.7 µg/m(3), short-term exposure to current level of PM(2.5) might increase both the all-cause daily mortality and daily emergency visits in China.

LncRNA FER1L4 suppressed cancer cell growth and invasion in esophageal squamous cell carcinoma.

OBJECTIVE: To investigate the regulatory effect of long non-coding ribonucleic acid (lncRNA) FER1L4 on biological behaviors of esophageal squamous cell carcinoma (ESCC) cells, such as proliferation and invasion. PATIENTS AND METHODS: The expressions of FER1L4 were detected in 42 pairs of ESCC tissues and corresponding para-carcinoma tissues and 5 kinds of ESCC cell lines via quantitative reverse transcription-polymerase chain reaction (qRT-PCR). Polyethyleneimine (PEI) and liposomes were used for FER1L4 expression or interference elimination assays, respectively. The proliferation and invasion of ESCC cells were detected via MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide), apoptosis assay, cell cycle assay, and transwell chamber. RESULTS: Results of qRT-PCR showed that, compared with that in normal tissues, FER1L4 was lowly expressed in ESCC tissues. Overexpression of FER1L4 could inhibit cell proliferation and invasion, promote apoptosis and increase the cell cycle distribution in G0/G1 phase. Knockout of FER1L4 could promote the proliferation and invasion of ESCC cells, inhibit apoptosis and decrease the cell cycle distribution in G0/G1 phase. CONCLUSIONS: FER1L4 is involved in the occurrence and development of ESCC and plays a key role as a tumor suppressor gene in ESCC.

Effect of temperature on hepatic and renal uptake of components from University of Wisconsin solution.

In rat liver and kidney preservation, hepatic and renal uptake of 3H-adenosine, 3H-glutathione, and 3H-raffinose from University of Wisconsin solution and diffusion to the interstitial space were measured. At 4 degrees C only 0.38+/-0.47% and 2+/-0.92% of the total 3H-adenosine remained in the kidney and in the liver, respectively, but at 37 degrees C the amount remaining was 1+/-1% and 12+/-3% (P<0.001). Hepatic and renal uptake of the impermeant 3H-raffinose was unaffected by temperature. During flush out, interstitial accumulation of adenosine was significantly higher in livers than in kidneys and decreased during 24-h cold storage. Glutathione accumulation in the interstitial space was two orders of magnitude lower than 3H-adenosine accumulation and comparable to the impermeant raffinose. In summary, the bioavailability of components of preservation solutions at 4 degrees C is lower than at physiological temperatures, so that the application of cytoprotectants at 37 degrees C to organ donors, rather than simple addition to the cold storage solution, might improve cold storage preservation of livers and kidneys.

Adenosine deaminase inhibition attenuates reperfusion low flow and improves graft survival after rat liver transplantation.

BACKGROUND: Low flow or no flow is a prefinal step after reperfusion of hepatic allografts. Adenosine is an intrinsic key regulator of physiological and pathological hepatic blood flow. METHODS: In a model of rat liver transplantation, the effect of donor pretreatment with adenosine deaminase inhibitors (0, 0.1, 1, 10 micromol erythro-9-[2-hydroxy-3-nonyl]adenine) was studied on hepatic interstitial adenosine concentrations, microcirculatory flow, leukocyte adhesion, and graft survival by means of microdialysis sampling, intravital video microscopy, and laser Doppler flowmetry. RESULTS: Donor pretreatment with 1 micromol erythro-9-[2-hydroxy-3-nonyl]adenine increased interstitial adenosine concentrations 5- to 10-fold, for more than 24 hr of cold storage. In LDF studies, mean donor blood flow was increased from 420 +/- 42 perfusion units (PU) to 832 +/- 52 PU and from 475 +/- 79 to 720 +/- 81 PU after reperfusion, and in intravital video microscopy studies from 247 +/- 24 to 281 +/- 39 pl/sec. There was no difference in the number of leukocytes sticking, but a significantly lower percentage of leukocytes rolling (26.1 +/- 1.9 vs. 36.5 +/- 7.5%) along the endothelial wall in the treatment group. Transplant survival after 44 hr cold storage in UW solution was 8/10 in the treatment group and 1/13 in the control group. CONCLUSIONS: Donor pretreatment with erythro-9-[2-hydroxy-3-nonyl]adenine increases survival of critically injured liver grafts. Donor or recipient treatment rather than addition of protectants to cold storage solutions are successful strategies to overcome preservation injury and possibly adverse donor factors.

Experimental transplantation of size-reduced, adult kidneys into pediatric recipients.

BACKGROUND: Renal transplantation in infants is frequently complicated by graft thrombosis and accelerated rejection reactions. We herein tested the hypothesis that the amount of blood required to sustain normal perfusion of an adult renal allograft transplanted into a pediatric recipient would surpass the cardiac output and aortic blood flow of the recipient and that the ensuing low flow in full-size grafts (FSG) would induce a release of thrombogenic substances. METHODS: In a porcine renal transplant model, adult FSG were transplanted into pediatric recipients. Macro- and microhemodynamic as well as metabolic data were recorded. Surgically size-reduced grafts (RSG) served as controls. RESULTS: Donor weight was 55.1+/-4.8 kg and 9.6+/-0.9 kg for recipients. FSG weight was 122+/-16 g and 65+/-14 g for RSG. Blood flow in donor kidneys was 20% higher than the infrarenal aortic blood flow of recipients. After reperfusion, mean arterial pressure in recipients of FSG but not RSG dropped to 64 mmHg, despite an increase in cardiac output by 60%. FSG but not RSG were polyuric and proteinuric. The release of endothelin and thromboxane B2 into the circulation was higher from FSG when compared with RSG (P<0.05 for endothelin after 60 min; NS for thromboxane B2). CONCLUSIONS: After transplantation of FSG into pediatric recipients, the macrohemodynamic limitations of the recipient cause microcirculatory disturbances in the graft, which contribute to the release of vasoconstrictive and prothrombotic substances and an impaired early graft function. Some of those effects can be ameliorated by surgically size reducing the renal graft.

[Five years' epidemiologic study of intoxication of pesticide use in a county].

The Intoxication of Pesticide Use (IPU) in a county since 1984-1988 was studied 1,345 cases of intoxication were found and two of them died among 732,128 persons investigated during those five years. The incidence rates of IPU were 0.410 8%, 0.166 7%, 0.052 1%, 0.205 7% and 0.090 5% respectively. Analysis on the relationship between the IPU and air temperature showed that they had a positive correlation (r = 0.886, P less than 0.01), indication that air temperature was one of important factors that affected the occurrence of IPU. Suggestions were made for the prevention of IPU.

[Effect of processing contents of saccharides in Danggui].

OBJECTIVE: To explore the effect of processing on the contents of saccharides in Danggui. METHOD: The contents of reducing saccharides, water-soluble saccharides and poly saccharides in Danggui and its processed products were determined by phenol-H2SO4 method. RESULTS: The contents of saccharides in the alcohol-broiled product were higher than those in the crude drug. CONCLUSION: Different processing methods have significant effects on the above saccharides, which administers to the interpreparation of the theory of Danggui processing.

High- or low-potassium solutions for the storage of abdominal and thoracic organs.

BACKGROUND: Clinically, intracellular type solutions are the most widely used solutions to preserve organs. The optimal ion composition of preservation solutions, however, is still unknown and extracellular-type solutions have frequently been superior to intracellular solutions in various experimental studies. MATERIALS AND METHODS: In this study, we measured extracellular (interstitial) electrolyte concentrations in rat livers, kidneys, hearts and lungs at 4 degrees C by means of microdialysis sampling. RESULTS: After 24 h cold ischaemia, [Na+]int and [K+]int were 104 +/- 25 mmol/l and 6.5 +/- 0.7 mmol/l in hearts, 92 +/- 12 mmol/l and 6.9 +/- 1.0 mmol/l in livers, 115 +/- 22 mmol/l and 6.3 +/- 0.9 mmol/l in kidneys and 87 +/- 17 mmol/l and 6.4 +/- 0.6 mmol/l in lungs. After preservation of organs in intracellular-type solutions, [Na+]int was significantly lower for each organ (range from 69 +/- 8 mmol/l to 73 +/- 20 mmol/l) and [K+]int was significantly higher (range from 8.0 +/- 1.7 mmol/l to 9.8 +/- 1.0 mmol/l). In no instance did the interstitial electrolyte concentration equilibrate with the intracellular electrolyte concentration. When the diffusion gradient from the vascular space to the interstitial space was calculated for Na+ and K+, a significantly higher barrier was found for K+ than for Na+ (P<0.001 and P<0.01 for hearts). CONCLUSIONS: These studies indicate that during cold storage of rat hearts, lungs, livers and kidneys, intra- and extracellular electrolytes do not equilibrate. Ion exchange stabilises at extracellular Na+ concentrations between 87 mmol/l and 115 mmol/l and K+ concentrations between 6.3 mmol/l and 6.9 mmol/l. Storage of organs in solutions with extracellular-type ion compositions might improve graft function and survival not only after lung and liver but also after heart and renal preservation.

Interstitial accumulation of Na+ and K+ during flush-out and cold storage of rat livers: implications for graft survival.

Intracellular-type electrolyte solutions were introduced into organ preservation to prevent K+ efflux and Na+ and Cl- influx into cells and cell swelling during cold ischemia. We studied cation accumulation in the interstitial space by microdialysis, during rat liver cold storage and after flush-out with high-K+ and low-K+ solutions. The effect of Na+ and K+ on graft function and survival was studied in an isolated perfused liver model and an orthotopic transplantation model after rat liver storage in iso-osmolar high-K+ and low-K+ solutions. After 24 hours of cold ischemia [Na+]o dropped from 136 +/- 2 mmol/L to 91.8 +/- 1.1 mmol/L, and [K+]o increased from 5.9 +/- 0.1 mmol/L to 12.2 +/- 1.6 mmol/L (P < .001 vs. control). [Na+]o and [K+]o after flush-out did not equilibrate with [Na+]sol and [K+]sol after 24 hours of cold storage. Rat livers preserved in low-K+ solutions produced significantly more bile during isolated reperfusion and released less alanine transaminase, aspartate transaminase, and lactate dehydrogenase into the reperfusion medium than high-K+ solutions. Rat liver survival after 14 hours of preservation was higher in low-K+ solutions (13 of 13) than in high-K+ solutions (7 of 13). Those studies indicate that during cold storage of rat livers, transmembraneous Na+-K+ sodium-potassium exchange might not follow the 3:2 stochiometry of a sole sodium-potassium exchange via Na+-K+ sodium-potassium adenosine triphosphatase (ATPase), and that low-K+ solutions might improve graft function and survival after rat liver preservation.

Hyperthermia-induced HSP expression correlates with improved rat renal isograft viability and survival in kidneys harvested from non-heart-beating donors.

Transient sublethal hyperthermia followed by recovery from heat stress, referred to as heat shock preconditioning, exerts a protective effect on ischemia/reperfusion-induced injury in many systems. This effect is considered to be correlated to heat shock proteins (HSPs) and might be a critical factor in kidney graft function and survival. This study was designed to examine the impact of heat shock preconditioning on kidney isograft function and survival in a model utilizing non-heart-beating (NHB) donors. Four groups of male Lewis rats (n = 10/group) subjected either to whole body hyperthermia (groups A and C) or to sham anesthesia (groups B and D) were allowed 24 h recovery. Thereafter, 20 min of warm ischemia (A/B), and in a separate set of experiments 40 min of warm ischemia (C/D), were induced by suprarenal aortic cross clamping before renal procurement. After 24-h preservation with University of Wisconsin solution at 4 degrees C, orthotopic kidney transplantations were performed to syngeneic bilaterally nephrectomized recipients. Tissue specimens were taken to determine HO-1/HSP32, 72, and 90 induction by Western blot analysis. Renal function was measured by means of serum creatinine and creatinine clearance on days 0, 3, and 7 as well as urine volume, protein content, and creatinine levels daily. HO-1/HSP32 and HSP72 were found to be expressed constitutively. Moreover, heat shock strongly induced renal HSP72 and HSP32/HO-1, and to a lesser extent HSP90, expression. For recipients of group A grafts, the graft survival rate was 10/10, whereas it was 7/10 (70 %) in recipients of group B grafts (log rank p < 0.05). Following 40 min of warm ischemia, 6/10 (60 %) recipients survived, whereas all sham treated animals died with anuria within 6 days (log rank p = 0.01). Heat shock preconditioning strongly improved graft viability and reduced functional impairment. Creatinine clearance (CRC) on day 3 post Tx was 0.43 +/- 0.24 ml/min in preconditioned animals (group A) and 0.07 +/- 0.09 ml/min (p < 0.001) in sham preconditioned (group B), whereas it was 0.91 +/- 0.33 ml/min and 0.03 +/- 0.02 ml/min (p < 0.00 001) on day 7 post Tx. Following 40 min NHB time, CRC in survivors of preconditioned graft recipients (group C) was 0.32 +/- 0.2 ml/min (day 3 post Tx) and 0.23 +/- 0.08 ml/min (day 7 post Tx) and was significantly better than CRC of group B (p < 0.01 and p < 0.00001, respectively). CRCs prior to NHB procedures were comparable in all animals ranging between 1.31 and 1.72 ml/min. Serum creatinine as well as proteinuria were significantly increased after transplantation in both groups but recovered within 5 days in recipients of preconditioned grafts, whereas kidneys from donors without HP did not recover function. Histological alterations were also diminished following HP. Hyperthermic preconditioning induces strong and long lasting HO-1/HSP32, HSP72, and HSP90 expression in rat kidneys. HP increases survival following transplantation and improves renal graft function including proteinuria, volume output, and creatinine clearance. HSP induction might be used to develop novel approaches in clinical transplantation.