[Serum glycocalyx markers in patients after cardiac arrest: association with outcomes].

Objective: To assess the levels of serum glycocalyx markers in the first 24 hours after cardiac arrest (CA) and investigate their relationship with 30-day outcomes. Methods: A retrospective cohort study was conducted on prospectively collected data from CA patients, who were admitted to the intensive care units of the Affiliated Hospital of Xuzhou Medical University and obtained return of spontaneous circulation for more than 24 hours between September 2021 and October 2022. Serum samples obtained at the 24-hour after CA were utilized to measure the levels of glycocalyx markers, including heparan sulfate (HS), hyaluronic acid (HA), and syndecan-1 (Sdc-1). Patients were allocated into good function (CPC1-2) and poor function (CPC3-5) groups on the basis of cerebral performance category (CPC) at 30 days post-CA. Logistic regression analysis was used to determine the association between serum glycocalyx markers and neurological outcomes. Patients were regrouped in light of 30-d mortality and Cox regression analysis was used to determine the association between serum glycocalyx markers and 30-d mortality. Results: A total of 71 patients were included in the study, including 31 (43.7%) females and 40 (56.3%) males, with an average age of (59.0±17.0) years. The poor function group (n=49) demonstrated significantly elevated levels of HS and HA when compared to the good function group (n=22) [HS: 2 461.0(1 623.0, 5 492.0) µg/L vs 1 492.0 (914.0, 2 550.0) µg/L, P=0.008; HA: 124.0(97.0, 365.0)µg/L vs 337.0(135.0, 1 421.0) µg/L, P=0.033]. Adjusted logistic regression analysis revealed that HS was independently associated with poor neurological outcome [odds ratio (OR)=0.389, 95% confidence interval (CI): 0.182-0.828, P=0.014]. In the 30-day mortality analysis, the death group (n=32) exhibited significantly higher levels of HS and HA when compared to the survival group (n=39) [HS: 1 880.0(1 011.0, 3 554.0) µg/L vs 2 500.0(1 726.0, 6 276.0) µg/L, P=0.027; HA: 162.0(99.0, 537.0) µg/L vs 813.0(148.0, 1 531.0) µg/L, P=0.025]. Adjusted Cox regression analysis indicated that elevated levels of HS and HA were independent risk factors (HS: HR=1.697, 95%CI: 1.126-2.557, P=0.011; HA: HR=1.336, 95%CI: 1.047-1.705, P=0.020) for 30-day mortality. Conclusions: High level of serum HS in 24 hours after CA may serve as a potential predictive marker for both neurological function and 30-day mortality. However, high level of serum HA appears to primarily predict 30-day mortality. Sdc-1 does not seem to contribute to outcome prediction.

[Adrenocortical oncocytic tumors: a clinicopathological analysis of 44 cases].

Objective: To study the clinicopathological features of adrenocortical oncocytic tumors (ACOT) and to compare the diagnostic values of Lin-Weiss-Bisceglia (LWB) score and Helsinki score. Methods: Forty-four cases of ACOT diagnosed at Beijing Friendship Hospital, China from March 2008 to July 2019 were histologically analyzed to evaluate their malignant potential (benign versus malignant) according to two scoring criteria. Immunohistochemical studies (EnVision method) were also used. Results: There were 23 males and 21 females with an average age of 46 years. Histologically, the tumor cells were arranged in trabecular, chrysanthemum-shaped, glandular and microcapsule structures, while clear cells were rare or absent. Most of the tumor cells were moderately atypical, and intranuclear inclusion bodies were conspicuous. Immunohistochemical staining showed that tumor cells were positive for Melan A, inhibin, Syn and calretinin. The average proliferation index was 3% in benign ACOT, about 5% in ACOT of malignant potential, and>20% in malignant ACOT. According to the LWB score, 61.4% (27/44) of the tumors were on the left side and had multiple lesions. The percentage of benign ACOT was 59.1% (26/44), malignant potential 6.8% (3/44), malignant 34.1% (15/44), respectively. Among the 15 malignant ACOT, the mitotic figures>5/50 HPF were found in 13 cases, necrosis in 11 cases and capsule invasion in 10 cases. According to the Helsinki score, 65.9% (29/44) of the tumors were benign, and 34.1% (15/44) were malignant. There was no significant difference between the two scoring standards (P>0.05). During the follow-up of 9 to 144 months, 31 patients survived without disease and 13 patients relapsed or had metastasis. Conclusions: ACOT more likely be benign than malignant. The left side is more common. Malignant tumors are prone to recurrence and metastasis. The morphological parameters (high mitotic index, necrosis, and capsular invasion) in the LWB scoring standards combined with immunohistochemical parameters (Ki-67) in the Helsinki score are helpful for the diagnosis of malignant ACOT and are important predictors of poor prognosis.

False-positive Aspergillus galactomannan immunoassays associated with intravenous human immunoglobulin administration.

OBJECTIVES: Evidence of false-positive galactomannan enzyme immunoassay (GM-EIA) results associated with intravenous immunoglobulin (IVIG) administration is scarce. Here, we aimed to determine the false-positive rate of GM-EIA after IVIG administration and to identify the related factors. METHODS: Standard GM-EIA was performed using diluted and pure human IVIG samples with and without heat treatment. We also included adult patients who had at least one GM-EIA result within 1 week of IVIG administration for analysis. Those who had prior invasive aspergillosis within 1 year before IVIG therapy were excluded. The clinical characteristics and galactomannan index (GMI) kinetics between patients with false-positive and true-positive GMI were compared. RESULTS: All diluted and pure IVIG samples tested positive for GM. Heat treatment resulted in the considerable elevation of GMI. Of 48 patients with positive GM-EIA results within 1 week of IVIG administration, 22 (45.8%) were considered to have false-positive antigenaemia (false-positive group, FPG). After the completion of IVIG administration, a decline in GMI was observed in all FPG patients but in only 18 out of 26 patients (69.2%) with true-positive results (true-positive group, TPG). By 7, 14, and 18 days of IVIG administration, GMI reverted to negative values in 7/15 (46.7%), 18/20 (90%) and 22/22 (100%) FPG patients, respectively, and 6/24 (25%), 14/24 (58.3%), and 16/26 (61.5%) of TPG patients, respectively. The TPG was more likely to have two or more consecutively positive GMIs after IVIG administration than the FPG (adjusted odds ratio, 9.01; 95% confidence interval, 1.99-40.9). CONCLUSIONS: IVIG treatment may produce false-positive GM-EIA results. A positive GMI among patients receiving human IVIG should be interpreted with caution.

Cataract risk of neuro-interventional procedures: a nationwide population-based matched-cohort study.

AIM: To demonstrate the risk of cataract associated with radiation exposure from neuro-interventional procedures. MATERIALS AND METHODS: This was a nationwide population-based, matched-cohort study. The exposed group (group E) comprised patients diagnosed with an aneurysm, cerebrovascular system anomaly, or subarachnoid haemorrhage who underwent a neuro-interventional procedure, such as brain digital subtraction angiography or endovascular embolisation. The comparison group (group C) included subjects who were never exposed to radiation from neuro-interventional procedures and were propensity score-matched by the date of enrolment, age, sex, and associated comorbidities. Multiple Cox proportional hazard regression analysis was used to estimate the hazard ratio (HR) of cataract risk due to radiation exposure while adjusting for potential confounding factors. RESULTS: There were 838 patients and 3,352 matched subjects in groups E and C, respectively. The incidence of cataracts was significantly greater among subjects in group E (adjusted HR [aHR] = 1.88; 95% confidence interval [CI] = 1.08-3.26), especially those aged >40 years (aHR = 2.14; 95% CI = 1.16-3.94). The number of computed tomography examinations was positively correlated, but not statistically significant, with an increased risk of cataract occurrence. CONCLUSIONS: Neuro-interventional procedures might be significantly associated with an increased risk of cataract occurrence.

[The impacts of testosterone on insulin sensitivity and chronic low-grade].

Objectives: Insulin resistance (IR) is a common manifestation in patients with polycystic ovarian syndrome (PCOS). Both clinical observations and animal studies have demonstrated that IR could be induced by hyperandrogenemia, which is the charac-teristic of PCOS.Nevertheless, the mechanisms of IR in PCOS are still unclear especially at the molecular level.We conduct this study to ellucidate the effects of androgen on insulin sensitivity and chronic low-grade inflammation in adult C57BL/6 female mice. Methods: Eleven adult female C57BL/6 mice aged 8 weeks weredaily injected with testosterone (1.0 mg/100 g body weight)which dissolved in sesame oil (experimental group T) for 16 weeks.Ten control mice were injected with sesame oil only (group Con). The changes of body weight and body fat content were detected.Intraperitoneal glucose tolerance tests (IGTT) were performed at 0, 2, 3 and 16 weeks treatment, blood from tail vein was taken to detect levels of glucose.Intraperitoneal insulin tolerance tests (ITT) were performed at 16 weeks treatment.Both groups were sacrificed after16 weeks treatment, and phosphorylation of GSK3ßand InsR, two molecules of insulin signaling pathway, were detected by Western blot from adipose tissue.The phosphorylation of NF-κBp65, CD16/32, and CD206 were also detected in adipose tissues.ELISA was used totest the serum IL-6 and MCP-1. Results: (1) No obvious significance of body weight as well as body fat content was detected between both experimental groups (P>0.05); (2) 2 weeks treatment with testosterone induced the in-crease of fasting blood glucose and displayed obvious significance compared with group Con (P<0.05); (3) 3 weeks treatment with testosterone induced the increase of area under the curve (AUC) of the blood glucose following IGTT and displayed significance compared with group Con (P<0.05). And more obvious significance was detected at 16 weeks treat-ment (P<0.01); (4) 16 weeks treatment with testosterone induced the increase of AUC of the blood glucose following ITT(P<0.01); (5) the serum IL-6 and MCP-1 in testosterone treat-ment was higher than that in thecontrols (P<0.05). And 16 weeks treatment with testosterone decreased phosphorylation of GSK3ß and InsR in C57BL/6 adipose tissues (P<0.05), in-creased phosphorylation of NF-κBp65.Testosteroneenhanced the expression of CD206, and decreased the expression of CD16/32. Conclusions: Treatment with testosterone in adult fe-male mice can induce insulin resistance by blocking insulin signal transduction, without in-fluencing body weight and body fat content.Testosterone could activate the NF-κB to pro-mote the expression of IL-6 and MCP-1. And testosterone facilitated to promote macro-phage to M1-subtype transformation.

[Effects and mechanism of testosterone on the production of inflammatory cytokines and glucose uptake in co-culture of RAW264.7 macrophage and 3T3-L1 adipocytes].

Objective: To investigate the effects of testosterone (T) on inflammatory cytokines (IL-6, MCP-1) production, insulin sensitivity of adipocyte and changes of macrophage phenotypes in indirect co-culture of RAW264.7 macrophages and 3T3-L1 adipocytes. Methods: 3T3-L1 preadipocytes were induced to mature in Transwell lower chamber, and then co-cultured with RAW264.7 macrophages in the upper chambers for 72 hours. Testosterone 10 µmol/L was added into indirect co-culture for 24 h. ELISA was used to testing IL-6, MCP-1 concentrations in supernatant. Western blot was used to detecting the phosphorylation of NF kappa B, ERK1/2, and theexpression of CD16/32 and CD206. Glucose transport was assessed by[3H]2-deoxy glucose uptake in adipocytes. Results: Testosterone enhanced inflammatory cytokines (IL-6, MCP-1) production in indirect co-culture of 3T3-L1 adipocytes and RAW264.7 macrophages, promoted the activation of ERK1/2 and nuclear factor kappa B p65, and inhibited glucose uptake in adipocytes. Testosterone facilitated the production of pro-inflammatory M1 macrophages. The above effects of testosterone can be completely reversed by PDTC, and can be partly reversed by PD98059 (70%-90%). Conclusion: NF kappa B and ERK1/2 could be the key proteins for testosterone to promote the production of inflammatory factors, to lead to insulin resistance, and to make macrophages differentiate to pro-inflammatory phenotypes in co-culture of RAW264.7 macrophages and 3T3-L1 adipocytes.

Identification of thioridazine, an antipsychotic drug, as an antiglioblastoma and anticancer stem cell agent using public gene expression data.

Glioblastoma (GBM) is a common and malignant tumor with a poor prognosis. Glioblastoma stem cells (GSCs) have been reported to be involved in tumorigenesis, tumor maintenance and therapeutic resistance. Thus, to discover novel candidate therapeutic drugs for anti-GBM and anti-GSCs is an urgent need. We hypothesized that if treatment with a drug could reverse, at least in part, the gene expression signature of GBM and GSCs, this drug may have the potential to inhibit pathways essential in the formation of GBM and thereby treat GBM. Here, we collected 356 GBM gene signatures from public databases and queried the Connectivity Map. We systematically evaluated the in vitro antitumor effects of 79 drugs in GBM cell lines. Of the drugs screened, thioridazine was selected for further characterization because it has potent anti-GBM and anti-GSCs properties. When investigating the mechanisms underlying the cytocidal effects of thioridazine, we found that thioridazine induces autophagy in GBM cell lines, and upregulates AMPK activity. Moreover, LC3-II was upregulated in U87MG sphere cells treated with thioridazine. In addition, thioridazine suppressed GBM tumorigenesis and induced autophagy in vivo. We not only repurposed the antipsychotic drug thioridazine as a potent anti-GBM and anti-GSCs agent, but also provided a new strategy to search for drugs with anticancer and anticancer stem cell properties.

Inducible cyclooxygenase expression mediating hypoxia/reoxygenation-induced pulmonary vasoconstriction is attenuated by a cyclooxygenase inhibitor in rats.

OBJECTIVE: Hypoxic pulmonary vasoconstriction (HPV) is a well known phenomenon to temporarily offset a ventilation-perfusion mismatch. Sustained HPV may lead to pulmonary hypertension. In this protocol, we studied the relationships between the HPV response and inducible cyclooxygenase II (COX II) activation after hypoxia-reoxygenation (H-R) challenge in an isolated perfused lung model. METHODS: An in situ isolated perfused rat lung model underwent inaction of hypoxia by ventilation with 5% CO(2)-95% N(2) for 10 minutes instead of 5% CO(2)-95% air; they were then reoxygenated with 5% CO(2)-95% air. We measured pulmonary arterial pressure (PAP) changes before, during, and after H-R challenge. We also estimated changes in blood concentrations of hydroxyl radicals, nitric oxide (NO) and thromboxane B(2) (TxB(2)) before and after H-R as well as mRNA expressions of COX II in lung tissue thereafter. A COX II inhibitor, celecoxib (10 mg/kg), was administered between 2 consecutive challenges. RESULTS: Hypoxia induced pulmonary vasoconstriction by increasing PAP (4.1 ± 0.8 mm Hg). Consecutive hypoxic challenges did not show tachyphylaxis (P > .05). H-R of lung tissues induced significant increases in blood concentrations of hydroxyl radicals (48.5 ± 7.6 vs 75.8 ± 11.5 mmol/L; P < .01), NO (54.3 ± 12.3 vs 77.7 ± 15.7 pmol; P < .05), and TxB(2) (42.3 ± 6.9 vs 58.7 ± 8.6 pg/mL; P < .05). Lung tissue H-R also significantly increased COX II mRNA expression compared with sham tissues (1 ± 0 vs 4.0 ± 2.8; P < .001). The COX II inhibitor celecoxib significantly attenuated HPV responses (P < .05) and attenuated the elevated blood concentrations of TxB(2) (P < .05), hydroxyl radicals (P < .01), nitric oxide (P < .05), and COX II mRNA expression (P < .05) after H-R challenge. CONCLUSIONS: Lung tissue H-R induced significant increases blood concentrations of inflammatory mediators and tissue mRNA expression of COX related to elevation of HPV responses. COX II inhibitor celecoxib attenuated the HPV responses by reducing TxB(2) release.

Protective effect of melatonin on liver ischemia-reperfusion induced pulmonary microvascular injury in rats.

OBJECTIVE: Reactive oxygen species generated during liver reperfusion have been implicated in remote lung injury. In this study, we evaluate the protective effects of melatonin pretreatment against the increased pulmonary microvascular permeability. METHODS: Male Sprague-Dawley rats were divided into three groups: shame-operated, liver ischemia-reperfusion (I/R), and melatonin pretreated (15 mg/kg, intraperitoneally) 15 minutes prior to the liver I/R). The duration of ischemia was 30 minutes, followed by 2 hours of reperfusion. Lungs were isolated in situ and parameters of the capillary filtration coefficient (K(fc)), lung wet-to-dry weight ratio (W/D), lung weight-to-body weight (LW/BW), and protein concentration in bronchial lavage fluid (PCBAL), the percentage of macrophages and neutrophils in bronchial lavage fluid (BALF), and lung tissue malonedealdehyde were used to assess the lung injury. RESULTS: Liver I/R-induced lung injury was noted by the markedly increased K(fc), W/D, LW/BW, PCBAL, and the presence of neutrophils and macrophages in BALF. Lipid peroxidation was also increased (P < .05). All indicators were markedly decreased in melatonin-pretreated rats (P < .05), suggesting that lung injury was attenuated. CONCLUSIONS: Melatonin pretreatment prior to liver I/R can effectively reduce the pulmonary microvascular permeability and attenuate lipid peroxidation in the lungs.

Liver reperfusion-induced decrease in dynamic compliance and increase in airway resistance are ameliorated by preischemic treatment with melatonin through scavenging hydroxyl radicals in rat lungs.

OBJECTIVES: Acute lung injury is frequently observed in patients subsequent to liver ischemia and reperfusion (I/R) injury. However, the changes in pulmonary function, eg, lung dynamic compliance (C(dyn)) and airway resistance (RI), are not well understood. We sought to study the alternations in pulmonary function during liver I/R and the protective effects of preischemic treatment with melatonin. METHODS: Animals were divided into 3 groups: sham-operated, liver I/R, and intraperitoneal (i.p.) pretreatment with melatonin (15 mg/kg). Liver I/R was performed by clamping the hepatic artery and portal vein for 30 minutes followed by releasing for 2 hours. The C(dyn) and RI were studied at baseline and at 2 hours of reperfusion. We assessed the level of pulmonary hydroxyl radicals by methylguanidine (MG) content in the bronchoalveolar lavage fluid (BALF) as well as the liver damage using plasma levels of lactate dehydrogenase (LDH), glutamic oxaloacetic transaminase (GOT), and glutamic pyruvic transaminase (GPT). RESULTS: After 2 hours of liver reperfusion, C(dyn) was reduced by ∼25%, while RI increased by ∼16% (P < .05). The decreased C(dyn) and increased RI were markedly attenuated by melatonin pretreatment (P < .05). Melatonin pretreatment also protected the liver against I/R injury (P < .05), as seen by reduced LDH, GOT and GPT along with markedly reduced hydroxyl radicals (P < .05). CONCLUSIONS: Preischemic treatment with melatonin protected lung function against damage by liver I/R. The improvement in lung function was strongly associated with decreased hydroxyl radicals in the lungs.

The protective effect of curcumin on ischemia-reperfusion-induced liver injury.

OBJECTIVE: Reperfusion of the ischemic liver results in the generation of oxidative and nitrosative stresses and reaction product of peroxynitrite, which induce rapid cytotoxicity and liver injury. In this study we demonstrated that curcumin, an antioxidant, attenuated ischemia/reperfusion (I/R)-induced liver injury. MATERIALS AND METHODS: Ischemia was induced by clamping the common hepatic artery and portal vein of rats for 30 minutes. Thereafter, flow was restored and the liver was reperfused for 80 minutes. Blood samples collected prior to ischemia and after reperfusion were analyzed for methyl guanidine (MG), nitric oxide (NO), tumor necrosis factor-alpha (TNF-α), and adenosphate triphosphate (ATP). Blood levels of serum glutamic oxaloacetic transaminase (sGOT), serum glutamate pyruvate transaminase (sGPT), and lactic dehydrogenase (LDH), which served as indexes of liver injury, were measured. RESULTS: The protocol resulted in elevation of blood NO (P < .001), TNF-α (P < .001), and MG (P < .001). sGOT, sGPT, and LDH were elevated significantly (P < .001), whereas ATP was significantly diminished (P < .001). Pretreatment with curcumin (25 mg/kg) significantly attenuated the reperfusion liver injury, while the ATP content reversed. In addition, MG, TNF-α, and NO release were attenuated. CONCLUSIONS: These results indicated that curcumin exerted potent anti-inflammatory effects in I/R-induced liver injury due to its antioxidant effects.

Cyclosporine, an immunosuppressant, attenuates phorbol-induced lung injury in rats.

OBJECTIVE: White cell activation in the lung plays a critical role to induce lung injury and lymphocytes in the thoracic duct system may also participate. We evaluated the effect of cyclosporine on phorbol myristate acetate (PMA)-induced lung injury. MATERIALS AND METHODS: We used an in situ isolated, blood perfused rat lung model to measure pulmonary arterial pressure (PAP) and lung weight gain (LWG; g) for 50 minutes after a bolus injection of PMA (0.05 microg/mL). Oxygen radical release was estimated by an LKB 1251 luminometer and by nitric oxide (NO) release as measured by an ENO-20 NO analyzer. RESULTS: In the group exposed to PMA alone, the mean PAP increased from 16.53 +/- 1.28 to 43.33 +/- 3.40 mm Hg (P < .001), and lung weight increased by 4.35 +/- 0.67 g during the 50-minute perfusion after PMA challenge (P < .001). In vitro measurement showed that PMA induced a significant increase in oxygen radical release (P < .001). PMA attenuated NO release (P < .001) into the perfusion system. Pretreatment with cyclosporine (3 mg/kg) for 3 days prevented the increases in both PAP (P < .01) and LWG (P < .001). NO release was maintained in cyclosporine-pretreated rats. Cyclosporine also showed dose-dependent attenuation of oxygen radical release by PMA-activated white blood cells. CONCLUSION: The mechanisms responsible for the protective effect of cyclosporine on the lung injury induced by phorbol may be related to an attenuation of oxygen radical production with maintenance of NO release.

Rat liver ischemia/reperfusion induced proinflammatory mediator and antioxidant expressions analyzed by gene chips and real-time polymerase chain reactions.

OBJECTIVE: Ischemia/reperfusion (I/R) of the rat liver induces injury; however, few studies have investigated gene expressions associated with this phenomenon. In this study, gene chip and real-time polymerase chain reactions (PCR) were used to study the expressions of the proinflammatory mediators and antioxidants after I/R. MATERIALS AND METHODS: Ischemia was induced by clamping the common hepatic artery and portal vein for 40 minutes followed by 90 minutes reperfusion. Blood samples collected before ischemia and after reperfusion were analyzed for alanine amino transferase, lactic dehydrogenase, hydroxyl radicals, nitric oxide (NO), and tumor necrosis factor alpha (TNFalpha). Expressions of TNFalpha, interleukin 12 (IL12), cyclooxygenase II (COXII), and other inflammatory mediators were analyzed by gene chips. COXII, TNFalpha, and antioxidants of mitochondrial superoxide dismutase (SOD(Mn)), catalase, and heat shock protein 70 (HSP70) were double confirmed by real-time PCRs. RESULTS: This protocol resulted in elevations in the blood concentrations of NO, hydroxyl radicals, TNFalpha, ALT, and LDH (P < .01) in the I/R but not the sham-operated group. Reperfusion induced significant increases in the expressions of TNFalpha, IL12, COXII, SOD(Mn), catalase, and HSP70. Real-time PCR also demonstrated increases in mRNA expressions of the proinflammatory mediators and antioxidants. CONCLUSIONS: This protocol resulted in oxidative stress, nitrosative stress, and liver injury. The increases in expressions of both proinflammatory mediators and antioxidants suggested that an imbalance between inflammation and anti-inflammation could be the possible reason for the liver injury after I/R.

Hypoxia and reoxygenation of the lung tissues induced mRNA expressions of superoxide dismutase and catalase and interventions from different antioxidants.

OBJECTIVE: Hypoxic pulmonary vasoconstriction (HPV) is a well-known phenomenon to temporarily offset a ventilation/perfusion mismatch. Sustained HPV may lead to pulmonary hypertension. In this protocol, we studied the relationships between the HPV response and oxygen radical release after hypoxia/reoxygenation (H/R) challenge in an isolated perfused lung model. MATERIALS AND METHODS: We used an in situ isolated rat lung preparation. Two hypoxic challenges (5% CO2-95% N2) were administered for 10 minutes each with administration of antioxidants of superoxide dismutase (SOD; 2 mg/kg), catalase (20,000 IU/kg), dimethylthiourea (DMTU; 100 mg/kg), dimethylsulfoxide (DMSO; 1 mL/kg), or allopurinol (30 mg/kg) between 2 challenges. We measured pulmonary arterial pressure changes before, during, and after H/R challenge. We measured blood concentration changes in hydroxyl radicals and nitric oxide (NO) before and after H/R. mRNA expressions of SOD and catalase in lung tissue were measured after the experiments. RESULTS: Hypoxia induced pulmonary vasoconstriction by increasing pulmonary arterial pressure and consecutive hypoxic challenges did not show tachyphylaxis. Blood concentrations of hydroxyl radicals and NO increased significantly after H/R challenges. mRNA expressions of SOD and catalase increased significantly, however, neither SOD nor catalase showed attenuated effects on HPV responses. Small molecules of DMTU, DMSO, and allopurinol attenuated the HPV responses. CONCLUSIONS: H/R induced increases in the expressions of SOD and catalase in lung tissues. DMTU, DMSO, and allopurinol antioxidants attenuated the HPV responses by reducing the oxygen radical release.

Non-lethal Candida albicans cph1/cph1 efg1/efg1 transcription factor mutant establishing restricted zone of infection in a mouse model of systemic infection.

The cph1/cph1 efg1/efg1 Candida albicans mutant cells were non-lethal in a mouse model of systemic infection. We investigated in vivo proliferation and invasion of C. albicans cells in infected mice to elucidate the interaction between the host and the pathogen. Homogenates of kidneys from the mice infected with the wild-type and the mutant C. albicans cells yielded a mean of 2.1 x 10 7 CFU/g and 2.2 x 10 6 CFU/g, respectively. The kidneys from the mice infected with the wild-type cells showed extensive renal cortical necrosis associated with neutrophilic infiltration. There were also wild-type hyphal cells present in abundance. Hence, tubular necrosis leading to renal failure in the mice may be the cause of death. Although the cph1/cph1 efg1/efg1 mutant cells were not lethal, they were capable of establishing restricted zones of infection and colonization near the renal pelvis instead of simply being cleared by the immune system in mice.

Prevalence, incidence, and mortality of PD: a door-to-door survey in Ilan county, Taiwan.

BACKGROUND: The reported prevalence and incidence rates of PD were significantly lower in China than those in Western countries. People in China and Taiwan have a similar ethnic background. OBJECTIVE: To investigate the prevalence, incidence, and mortality rate of PD in Taiwan. METHOD: The authors conducted a population-based survey using a two-stage door-to-door approach for patients aged 40 years or older in Ilan, Taiwan. Patients were diagnosed with PD by having at least two of the four cardinal signs of parkinsonism and exclusion of seconddary parkinsonism. To identify new cases of PD after the survey, patients with negative results of parkinsonism in the first stage were matched to the information on clinical diagnosis of PD from the Bureau of National Health Insurance toward the end of December 31, 1997. All cases of PD were linked to the Taiwan mortality registration to ascertain causes of deaths until December 31, 1999. RESULTS: The participation rate was 88.1% among the 11,411 contacted individuals. Thirty-seven cases of PD were identified. The age-adjusted prevalence rate of PD for all age groups was 130.1 per 100,000 population after being adjusted to the 1970 US census, assuming no cases of PD would be found among those younger than 40 years of age. Of 9972 non-PD subjects in the first screen, 15 new cases of PD were ascertained. The age-adjusted incidence rate was 10.4 per 100,000 population for all age groups. The case fatality rate of PD after a 7-year follow-up was 40.4% (21 deaths in 52 patients with PD). The relative risk of death for PD cases versus non-PD cases was 3.38 (95% CI: 2.05-4.34). The 5-year cumulative survival rate in PD cases (78.85%) was statistically lower than that in non-PD cases (92.84%). CONCLUSION: The prevalence and incidence rates of PD in Taiwan were much higher than those reported in China, but closer to those in Western countries. These results suggest that environmental factors may be more important than racial factors in the pathogenesis of PD.

Microscopic assessment of pronuclear embryos is not definitive.

The microscopic classification of embryos, especially unipronuclear embryos, is not very precise. A number of undocumented and unipronuclear embryos were determined to be diploid following karyotyping and fluorescence in situ hybridization (FISH). Accelerated and asynchronous pronuclear dismantling at the time of checking for embryo fertilization accounts for this disparity. Diploid embryos were also observed among tripronuclear embryos. However, not all embryos ascertained as diploid by FISH were karyotypically normal following full karyotype analysis. By taking into account the "background" abnormality rate, the rate of diploid embryo wastage was estimated to be about 40% among undocumented embryos and about 58% in total. A high percentage of misclassification infers an unintended loss of otherwise transferable embryos. Such a discrepancy is particularly important to older women who have fewer embryos. If these are a woman's only embryos, preimplantation genetic diagnosis might be applicable in determining those that are diploid and suitable for transfer. This could potentially reduce the number of wasted embryos and cycles. The present study has also shown that mosaicism is common but it is still unclear whether mosaicism is indicative of embryonic abnormality or is a fairly common phenomenon among healthy embryos. Bipronuclear embryos that present with abnormal or delayed cleavage are often chaotic in their chromosomal constitution. Such embryos should not be transferred.

Vascular invasion routes and systemic accumulation patterns of tobacco mosaic virus in Nicotiana benthamiana.

Plant viruses must enter the host vascular system in order to invade the young growing parts of the plant rapidly. Functional entry sites into the leaf vascular system for rapid systemic infection have not been determined for any plant/virus system. Tobacco mosaic virus (TMV) entry into minor, major and transport veins from non-vascular cells of Nicotiana benthamiana in source tissue and its exit from veins in sink tissue was studied using a modified virus expressing green fluorescent protein (GFP). Using a surgical procedure that isolated specific leaf and stem tissues from complicating vascular tissues, we determined that TMV could enter minor, major or transport veins directly from non-vascular cells to produce a systemic infection. TMV first accumulated in abaxial or external phloem-associated cells in major veins and petioles of the inoculated leaf and stems below the inoculated leaf. It also initially accumulated exclusively in internal or adaxial phloem-associated cells in stems above the inoculated leaf and petioles or major veins of sink leaves. This work shows the functional equivalence of vein classes in source leaves for entry of TMV, and the lack of equivalence of vein classes in sink leaves for exit of TMV. Thus, the specialization of major veins for transport rather than loading of photoassimilates in source tissue does not preclude virus entry. During transport, the virus initially accumulates in specific vascular-associated cells, indicating that virus accumulation in this tissue is highly regulated. These findings have important implications for studies on the identification of symplasmic domains and host macromolecule vascular transport.

Impact of oral submucous fibrosis on chemotherapy-induced mucositis for head and neck cancer in a geographic area in which betel quid chewing is prevalent.

In Southeast Asia and Taiwan, betel quid chewing is prevalent. Patients with head and neck cancer who chewed betel quid habitually seem to experience more severe chemotherapy-induced mucositis in our clinical practice. To validate this issue, patients with untreated head and neck cancer who received cisplatin (cDDP) plus a 5-fluorouracil (5-FU)-based neoadjuvant chemotherapy were included in this analysis. Information on the consumption of betel quid, tobacco, and alcohol were recorded before chemotherapy. Oral submucous fibrosis (OSF) was diagnosed clinically according to the fibrotic appearance of the mucosa and trismus. Mucositis was scored according to the World Health Organization criteria, and the mucositis score of the first course of chemotherapy was used for analysis. From December 1993 to April 1996, 120 patients were enrolled in this trial. Neither the betel quid chewing nor the cancer of the oral cavity was to be a significant factor for mucositis. However, clinically diagnosed OSF was found to display a significant correlation with more severe mucositis (p = 0.02). We concluded that in betel quid chewing-prevalent areas, OSF was a risk factor of more severe mucositis in head and neck cancer patients treated by CDDP and 5-FU-based regimens.