Elevation of serum lactate dehydrogenase at posterior reversible encephalopathy syndrome onset in chemotherapy-treated cancer patients

The pathophysiology of posterior reversible encephalopathy syndrome (PRES) is incompletely understood; however, an underlying state of immune dysregulation and endothelial dysfunction has been proposed. We examined alterations of serum lactate dehydrogenase (LDH), a marker of endothelial dysfunction, relative to the development of PRES in patients receiving chemotherapy. A retrospective Institutional Review Board approved database of 88 PRES patients was examined. PRES diagnosis was confirmed by congruent clinical diagnosis and MRI. Clinical features at presentation were recorded. Serum LDH values were collected at three time points: prior to, at the time of, and following PRES diagnosis. Student’s t-test was employed. LDH values were available during the course of treatment in 12 patients (nine women; mean age 57.8 years [range 33–75 years]). Chemotherapy-associated PRES patients were more likely to be normotensive (25%) versus the non-chemotherapy group (9%). LDH levels at the time of PRES diagnosis were higher than those before and after (p = 0.0263), with a mean difference of 114.8 international units/L. Mean time intervals between LDH measurement prior to and following PRES diagnosis were 44.8 days and 51.4 days, respectively. Mean elapsed time between last chemotherapy administration and PRES onset was 11.1 days. In conclusion, serum LDH, a marker of endothelial dysfunction, shows statistically significant elevation at the onset of PRES toxicity in cancer patients receiving chemotherapy. Our findings support a systemic process characterized by endothelial injury/dysfunction as a factor, if not the prime event, in the pathophysiology of PRES.     

Mapping of the hepatitis B virus attachment site by use of infection-inhibiting preS1 lipopeptides and tupaia hepatocytes

BACKGROUND & AIMS: Studies on the early steps in the life cycle of hepatitis B virus have been hampered by the lack of readily available target cells. In this study, we mapped a defined virus attachment site to primary hepatocytes that is essential for infection. METHODS: We used purified virus particles from human carrier plasma as an inoculum and primary cultures of tupaia hepatocytes as susceptible target cells and studied the inhibitory effect of amino-terminally acylated preS1-derived lipopeptides on infection interference. RESULTS: Infectivity of virus could be blocked efficiently in this system by amino-terminally acylated peptides containing amino acids 2-18 from the preS1 domain. The addition of amino acids 28-48 enhanced the inhibitory capacity, whereas amino acids 49-78 did not contribute to inhibition. Myristoylated preS1 peptides 2-48 bound strongly to tupaia hepatocytes but not to nonhepatic cells or rodent hepatocytes and thereby inhibited infection even at concentrations of 1 nmol/L completely. Particles consisting only of the small hepatitis B surface protein-the active component of current hepatitis B vaccines-did not bind at all to tupaia hepatocytes, but the addition of the preS1 domain to the particles allowed binding. CONCLUSIONS: The preS1 sequence 2-48 mediates attachment of the virus to its target cells, whereas the small surface protein seems to be involved in other steps. These findings indicate that the current subunit hepatitis B vaccines may be improved by the addition of distinct preS1 epitopes. Moreover, preS1 lipopeptides are promising candidates for specific antiviral therapy against hepatitis B infections.     

五味余甘子散对大鼠心肌缺血再灌损伤的保护作用

目的探讨藏方五味余甘子散对心肌缺血再灌损伤大鼠的保护作用。方法将96只SD大鼠随机均分成五味余甘子散高、中、低剂量组及伪手术组、模型组和阳性对照组,连续给药10 d,在末次给药24 h后,进行造模,结扎左冠前室间支30min,复灌40 min。测定血清中乳酸脱氢酶(LDH)、肌酸激酶(CK)的含量及心肌组织中超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GSH-Px)的活性和丙二醛(MDA)的含量,并比较各组心肌的超微结构变化。结果五味余甘子散能显著降低血清中LDH和CK的含量,同时能提高心肌组织中SOD、GSH-Px的活性,降低MDA的活性。结论五味余甘子散对大鼠心肌缺血再灌损伤有保护作用,其机制可能与抑制自由基相关酶有关。     

Assessment of pulmonary toxicity of MgO nanoparticles in rats

In this study, we have evaluated the pulmonary toxicity of MgO nanoparticles (MgO NPs) in rats following their exposure. NPs in phosphate buffered saline + 1% Tween 80 were exposed via intratracheal instillation at a doses of 1 mg/kg or 5 mg/kg into rat lungs and evaluated for various tissue damage markers like alkaline phosphatase (ALP) and lactate dehydrogenase (LDH) in bronchoalveolar lavage (BAL) fluid and histopathology of lungs at 1, 7, and 30 days of post‐exposure intervals. A dose‐dependant increase in ALP and LDH activity was observed in BAL fluids of rat lungs than sham control at all post‐exposure periods (P <0.05), and a dose‐dependant infiltration of interstitial lymphocytes, peribronchiolar lymphocytic infiltration, and dilated and/or congested vessels at 1 day post‐exposure period, worsened at 1 week period, and were reduced at 1 month at histology, indicating the pulmonary toxicity of MgO NPs. In conclusion, MgO NPs exposure produced a dose‐dependent pulmonary toxicity in rats and was comparable with that of Quartz particles. © 2013 Wiley Periodicals, Inc. Environ Toxicol 30: 308–314, 2015.     

Leukotrienes stimulate pepsinogen secretion from guinea pig gastric chief cells by a nitric oxide-dependent pathway

Leukotrienes (LTs) are involved in many inflammatory conditions including gastric damage induced by nonsteroidal anti-inflammatory drugs. Although LTs stimulate acid secretion, the effect they exert on pepsinogen secretion is unknown. The aim of this study was to investigate whether LTs stimulate pepsinogen secretion by isolated chief cells and to identify the intracellular messengers that mediate this action. Isolated chief cells were incubated with concentrations of LTB₄, LTC₄, LTD₄, or LTE₄ ranging from 0.1 pmol/L to 10 μmol/L, and pepsinogen release, intracellular calcium and inositol(1,4,5)-trisphosphate (IP₃) concentrations were measured. Nitric oxide generation was determined by the amount of citrulline generated during incubation. All four LTs caused a concentration-dependent stimulation of pepsinogen secretion with 50% effective concentration of 0.05-0.1 nmol/L and a dose-dependent increase in cytoplasmic free calcium and IP₃ concentration. The LTB₄ and LTD₄ antagonists caused selective, concentration-dependent inhibition of LTB₄- and LTD₄-induced pepsinogen secretion, calcium mobilization, and IP₃ generation. All four LTs increased NO generation, and the effect was inhibited by LTB₄ and LTD₄ antagonists and an NO synthase inhibitor N^G-monomethyl-l-arginine and reversed by l-arginine. N^G-monomethyl-l-arginine caused a 50%–60% reduction of LT-induced pepsinogen release. Each of the four LTs caused a fivefold increase in 5′-cyclic guanosine monophosphate. LTs are powerful stimulators of pepsinogen secretion in isolated chief cells and act via occupancy of specific cell-surface receptors.     

Mechanism of adrenocortical toxicity induced by quinocetone and its bidesoxy-quinocetone metabolite in porcine adrenocortical cells in vitro

Quinocetone (QCT) is a new feeding antibacterial agent in the QdNOs family. The mechanism of its adrenal toxicity is far from clear. This study was conducted to estimate the adrenal cell damage induced by QCT and its bidesoxy-quinocetone (B-QCT) metabolite and to further investigate their mechanisms. Following doses of QCT increasing from 5 to 50 μM, cell apoptosis and necrosis, mitochondrial dysfunction and redox imbalance were observed in porcine adrenocortical cells. The mRNA levels of the six components of intermediary enzymes and the adrenal renin-angiotensin-aldosterone system (RAAS) displayed a dysregulation induced by QCT, indicating that QCT might influence aldosterone secretion not only through the upstream of the production but also through the downstream of the adrenal RAAS pathway. In contrast, B-QCT had few toxic effects on the cell apoptosis, mitochondrial dysfunction and redox imbalance. Moreover, LCMS-IT-TOF analysis showed that no desoxy metabolites of QCT were found in either cell lysate or supernatant samples. In conclusion, we reported on the cytotoxicity in porcine adrenocortical cells exposed to QCT via oxidative stress, which raised awareness that its toxic effects resulted from N→O groups, and its toxic mechanism might involve the interference of the steroid hormone biosynthesis pathway.     

A Superinfection of Salmonella typhi and Hepatitis E Virus Causes Biphasic Acute Hepatitis

A 47-year-old Japanese man was referred to our hospital because of a sustained high fever with diarrhea 12 days after a flight from India. Liver enzymes were elevated with rose spots, hepatosplenomegaly, relative bradycardia, and acute cholecystitis. A liver biopsy depicted the dense infiltration of lymphocytes and Kupffer cells in sinusoids and the granulomatous formation in the parenchyma. The liver damage was initially resolved with the administration of ceftriaxone for 16 days but flared up 1 week later. Laboratory tests yielded positive reactions for Salmonella typhi and hepatitis E virus RNA. The pathophysiological presentations of concurrent typhoid and type E hepatitis are discussed.     

Thoracentesis in patients with hematologic malignancy: yield and safety

BACKGROUND: Pleural effusions occur in patients with hematologic malignancies, particularly during periods of hospitalization. Thoracentesis is often performed to diagnose infection and to exclude the presence of complicated parapneumonic effusions. The efficacy and safety of thoracentesis in this setting has not been well-studied. DESIGN: Retrospective chart review of hospitalized patients with hematologic malignancies undergoing thoracentesis. The aim of this study was to assess the role of thoracentesis in establishing a diagnosis of infection in this population and to determine the risk of complications. RESULTS: A total of 100 thoracentesis findings were analyzed in patients with lymphoma (52 patients) and leukemia (27 patients), and in patients who had undergone bone marrow or stem cell transplantation (21 patients). The indication for performing thoracentesis was to exclude infection in 69% of cases. Fever was present in 59% of the patients, and a concomitant lung parenchymal abnormality was present in 69% of cases. Effusions were moderate to large in size (87% of cases), and were both bilateral (62%) and unilateral (38%). Exudates were documented in 83%of the cases. A specific diagnosis was found in 21 patients and was more frequently established in those with lymphoma (31%) compared to the other groups of patients. Diagnoses found included malignancy in 14 cases, chylous effusions in 6 cases, and infection in 1 case. The one patient in whom empyema was found required drainage. The criteria for a parapneumonic effusion were not found in any other patients. The complication rate of 9% (pneumothorax, seven patients; hemothorax, two patients) was comparable to that in other populations of patients. CONCLUSIONS: Despite a high propensity for developing pulmonary infections, hospitalized patients with hematologic malignancies rarely developed complex parapneumonic effusions. The etiology of many of the effusions that occurred in this setting was unclear.     

Cardiac Troponin I association with critical illness and death risk in 726 seriously ill COVID-19 patients: A retrospective cohort study

Background: For coronavirus disease 2019 (COVID-19), early identification of patients with serious symptoms at risk of critical illness and death is important for personalized treatment and balancing medical resources.Methods: Demographics, clinical characteristics, and laboratory tests data from 726 patients with serious COVID-19 at Tongji Hospital (Wuhan, China) were analyzed. Patients were classified into critical group (n = 174) and severe group (n= 552), the critical group was sub-divided into survivors (n = 47) and non-survivors (n = 127).Results: Multivariable analyses revealed the risk factors associated with critical illness in serious patients were: Advanced age, high respiratory rate (RR), high lactate dehydrogenase (LDH) level, high hypersensitive cardiac troponin I (hs-cTnI) level, and thrombocytopenia on admission. High hs-cTnI level was the independent risk factor of mortality among critically ill patients in the unadjusted and adjusted models. ROC curves demonstrated that hs-cTnI and LDH were predictive factors for critical illness in patients with serious COVID-19 whereas procalcitonin and D-Dimer with hs-cTnI and LDH were predictive parameters in mortality risk.Conclusions: Advanced age, high RR, LDH, hs-cTnI, and thrombocytopenia, constitute risk factors for critical illness among patients with serious COVID-19, and the hs-cTnI level helps predict fatal outcomes in critically ill patients.