Blood Lactate Dehydrogenase Levels Research Articles

Patient Characteristics Associated with Growth of Patient-Derived Tumor Implants in Mice (Patient-Derived Xenografts).

Background: patient-derived xenografts (PDXs) have defined the field of translational cancer research in recent years, becoming one of the most-used tools in early drug development. The process of establishing cancer models in mice has turned out to be challenging, since little research focuses on evaluating which factors impact engraftment success. We sought to determine the clinical, pathological, or molecular factors which may predict better engraftment rates in PDXs. Methods: between March 2017 and January 2021, tumor samples obtained from patients with primary or metastatic cancer were implanted into athymic nude mice. A full comprehensive evaluation of baseline factors associated with the patients and patients' tumors was performed, with the goal of potentially identifying predictive markers of engraftment. We focused on clinical (patient factors) pathological (patients' tumor samples) and molecular (patients' tumor samples) characteristics, analyzed either by immunohistochemistry (IHC) or next-generation sequencing (NGS), which were associated with the likelihood of final engraftment, as well as with tumor growth rates in xenografts. Results: a total of 585 tumor samples were collected and implanted. Twenty-one failed to engraft, due to lack of malignant cells. Of 564 tumor-positive samples, 187 (33.2%) grew at time of analysis. The study was able to find correlation and predictive value for engraftment for the following: the use of systemic antibiotics by the patient within 2 weeks of sampling (38.1% (72/189) antibiotics- group vs. 30.7% (115/375) no-antibiotics) (p = 0.048), and the administration of systemic steroids to the patients within 2 weeks of sampling (41.5% (34/48) steroids vs. 31.7% (153/329), no-steroids) (p = 0.049). Regarding patient's baseline tests, we found certain markers could help predict final engraftment success: for lactate dehydrogenase (LDH) levels, 34.1% (140/411) of tumors derived from patients with baseline blood LDH levels above the upper limit of normality (ULN) achieved growth, against 30.7% (47/153) with normal LDH (p = 0.047). Histological tumor characteristics, such as grade of differentiation, were also correlated. Grade 1: 25.4% (47/187), grade 2: 34.8% (65/187) and grade 3: 40.1% (75/187) tumors achieved successful growth (p = 0.043), suggesting the higher the grade, the higher the likelihood of success. Similarly, higher ki67 levels were also correlated with better engraftment rates: low (Ki67 < 15%): 8.9% (9/45) achieved growth vs. high (Ki67 ≥ 15%): 31% (35/113) (p: 0.002). Other markers of aggressiveness such as the presence of lymphovascular invasion in tumor sample of origin was also predictive: 42.2% (97/230) with lymphovascular vs. 26.9% (90/334) of samples with no invasion (p = 0.0001). From the molecular standpoint, mismatch-repair-deficient (MMRd) tumors showed better engraftment rates: 62.1% (18/29) achieved growth vs. 40.8% (75/184) of proficient tumors (p = 0.026). A total of 84 PDX were breast models, among which 57.9% (11/19) ER-negative models grew, vs. 15.4% (10/65) of ER-positive models (p = 0.0001), also consonant with ER-negative tumors being more aggressive. BRAFmut cancers are more likely to achieve engraftment during the development of PDX models. Lastly, tumor growth rates during first passages can help establish a cutoff point for the decision-making process during PDX development, since the higher the tumor grades, the higher the likelihood of success. Conclusions: tumors with higher grade and Ki67 protein expression, lymphovascular and/or perineural invasion, with dMMR and are negative for ER expression have a higher probability of achieving growth in the process of PDX development. The use of steroids and/or antibiotics in the patient prior to sampling can also impact the likelihood of success in PDX development. Lastly, establishing a cutoff point for tumor growth rates could guide the decision-making process during PDX development.

Association of the lung immune prognostic index with the survival of patients with idiopathic interstitial pneumonias.

The lung immune prognostic index (LIPI), a simple index calculated from the blood lactate dehydrogenase level and derived neutrophil-to-lymphocyte ratio, is thought to be associated with host immune status. However, the utility of LIPI in patients with idiopathic interstitial pneumonias (IIPs) is unknown. In this multicentre, retrospective, observational study, an association between LIPI and the survival of patients with IIPs was evaluated. Exploratory and validation cohorts consisting of 460 and 414 patients with IIPs, respectively, were included (159 and 159 patients had idiopathic pulmonary fibrosis [IPF], and 301 and 255 had non-IPF, respectively). In the exploratory cohort, patients with IPF and a low LIPI had significantly better survival than those with a high LIPI (median of 5.6 years vs. 3.9 years, p = 0.016). The predictive ability of LIPI for the survival of patients with IPF was validated in the validation cohort (median of 8.5 years vs. 4.4 years, p = 0.003). In a multivariate Cox proportional hazard analysis, LIPI was selected as an independent predictive factor for the survival of IPF patients. There was no significant association between LIPI and survival of non-IPF patients in the exploratory and validation cohorts. The LIPI was a predictive factor for the survival of patients with IPF and could aid the management of IPF.

Abstract 2177: Roles of lactate dehydrogenase (LDH) in melanoma: an underestimated prognostic biomarker

Abstract Introduction: High LDH activity is associated with a poor prognosis in many cancer types, especially in melanoma where it is the strongest indicator of poor outcome even with the most potent anticancer immunotherapies or targeted therapies. Although high LDH blood activity is often associated with high tumor burden, this is not always the case and there is no definitive demonstration that blood LDH activity is directly derived from tumors cells. Our objectives were 1) to explore the biological impact of LDHA and LDHB independently of their metabolic function 2) to explore the respective prognostic values of the 5 LDH isoforms as well as the relationship between tumor and blood LDH isoforms repartition in melanoma patients. Material, Patients, Methods: A375 melanoma cells cultured in glucose or galactose (to evaluate glycolytic independent effects) were silenced for LDHA or LDHB expression using si-RNAs. RNAseq analysis of total RNAs and polysomal RNAs was performed to explore the transcriptional and translational impacts of LDHA and LDHB expression. In melanoma patients treated with immunotherapy, the enzymatic activities of each of the 5 LDH isoforms (encoded by LDHA and LDHB) were measured in tumors and blood samples. The prognostic values of the distinct isoforms as well as the correlation between the isoforms distribution in blood and tumors were evaluated. Results: In vitro, independently of their metabolic effect, both LDHA and LDHB had distinct transcriptional and translational impacts on the control of several key oncogenic pathways (adhesion, survival, proliferation, immunity) with a more important effect of LDHA vs LDHB silencing. In vivo, among 64 melanoma patients including 25% with high LDH, high LDH1 (B4) activity was significantly associated with response and overall survival (OS) whereas high LDH4 (A3B1) was inversely associated with response and OS. LDH1 and LDH4 were associated with survival even among patients with normal LDH levels. For patients with paired (tumor and blood) isoforms analysis, there was no correlation between isoforms repartition suggesting that blood LDH activity is not directly related to tumor LDH. Conclusion: In addition to their metabolic activity, LDH enzymes, particularly LDHA, control several key oncogenic pathways at the transcriptional level but also at the translational level for a set of genes involved in cancer biology. LDH1 and LDH4 isoforms blood levels are differentially correlated with response to immunotherapy and survival. They are more robust prognostic biomarkers than total blood LDH level used in our daily practice. Thus, LDH is much more than just a marker of tumor burden in melanoma and the origins, the significance and the roles of blood LDH isoforms need to be revisited. These results highlight the need to develop anticancer drugs targeting LDH, and especially LDHA. Citation Format: Laura Soumoy, Virginie Quidville, Lisa Fredeau, Giuseppina Claps, Caroline Pradon, Ludovic Lacroix, Emilie Routier, Djaouida Belkadi, Séverine Roy, Feras Chehade, Stephan Vagner, Caroline Robert. Roles of lactate dehydrogenase (LDH) in melanoma: an underestimated prognostic biomarker [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 2177.

Serious complications in COVID-19 ARDS cases: pneumothorax, pneumomediastinum, subcutaneous emphysema and haemothorax.

The novel coronavirus identified as severe acute respiratory syndrome-coronavirus-2 causes acute respiratory distress syndrome (ARDS). Our aim in this study is to assess the incidence of life-threatening complications like pneumothorax, haemothorax, pneumomediastinum and subcutaneous emphysema, probable risk factors and effect on mortality in coronavirus disease-2019 (COVID-19) ARDS patients treated with mechanical ventilation (MV). Data from 96 adult patients admitted to the intensive care unit with COVID-19 ARDS diagnosis from 11 March to 31 July 2020 were retrospectively assessed. A total of 75 patients abiding by the study criteria were divided into two groups as the group developing ventilator-related barotrauma (BG) (N = 10) and the group not developing ventilator-related barotrauma (NBG) (N = 65). In 10 patients (13%), barotrauma findings occurred 22 ± 3.6 days after the onset of symptoms. The mortality rate was 40% in the BG-group, while it was 29% in the NBG-group with no statistical difference identified. The BG-group had longer intensive care admission duration, duration of time in prone position and total MV duration, with higher max positive end-expiratory pressure (PEEP) levels and lower min pO2/FiO2 levels. The peak lactate dehydrogenase levels in blood were higher by statistically significant level in the BG-group (P < 0.05). The contribution of MV to alveolar injury caused by infection in COVID-19 ARDS patients may cause more frequent barotrauma compared to classic ARDS and this situation significantly increases the MV and intensive care admission durations of patients. In terms of reducing mortality and morbidity in these patients, MV treatment should be carefully maintained within the framework of lung-protective strategies and the studies researching barotrauma pathophysiology should be increased.

Chitosan oligosaccharide combined with running benefited the immune status of rats

Chitosan oligosaccharide (COS) degraded by chitosan, is an easily accessible and biocompatible natural molecule, which can facilitate the immune system. Running is one of the most effective forms of exercise. Persistence in running can effectively improve the body's resistance against pathogens. However, whether the combination of COS and running could benefit immune status still remains to be elucidated. We used Sprague-Dawley (SD) rats to explore the combinatory effect of COS and running. The organs and blood of the rats were collected after four weeks and the organ body mass index, biochemical and blood routine examination, cytokines, and T cells in the spleen and blood were detected and analyzed. In the group intragastric administration of COS only, the level of blood lactate dehydrogenase was increased, while the blood creatinine, red blood cells, lymphocytes, and serum TNF were decreased. Furthermore, COS combined with running promoted the development of spleen and lung, the level of lymphocytes, T cell and CD8+ T cell ratio in the blood, and serum TNF level. At the same time, the level of lactate dehydrogenase, serum IL-2, and T cell ratio in spleen were decreased. Therefore, our study indicated that COS combined with running could improve the immune status of rats.

The Impact of Aspirin Intake on Lactate Dehydrogenase, Arterial Stiffness, and Oxidative Stress During High-Intensity Exercise: A Pilot Study.

Aspirin is a common nonsteroidal anti-inflammatory drug used to reduce fever, pain, and inflammation. However, aspirin’s anti-inflammatory properties may also prevent increased levels of blood lactate dehydrogenase, vascular arterial stiffness and oxidative stress induced by high-intensity exercise. The purpose of this study was to investigate the effects of 4 weeks of aspirin supplementation on lactate dehydrogenase activity, lactate, arterial stiffness, and antioxidant capacity during high-intensity exercise in Taekwondo athletes. Participants were randomly divided into two groups: aspirin supplementation (n = 10) and placebo-control (n = 10). Blood levels of lactate dehydrogenase (LDH) enzyme activity and lactate were assessed to examine muscle damage and carotid-to-radial pulse wave velocity and the augmentation index were measured to examine arterial stiffness. Blood levels of superoxide dismutase, malondialdehyde, and glutathione peroxidase were assessed to determine antioxidant capacity and levels of oxidative stress. There were significant group × time interactions for enzyme activity of LDH (Δ-60 ± 24.36 U/L) and carotid-to-radial pulse wave velocity (Δ-1.33 ± 0.54 m/s), which significantly decreased (p < 0.05) following aspirin supplementation compared to placebo-control. Superoxide dismutase (Δ359 ± 110 U/gHb) and glutathione peroxidase (Δ28.2 ± 10.1 U/gHb) significantly decreased while malondialdehyde (0Δ3.0 ± 0.1 mmol/mL) significantly increased (p < 0.05) in the placebo-control group compared to the supplementation group. However, there were no changes in lactate concentration levels or augmentation index. These results reveal that low-dose aspirin supplementation would be a useful supplementation therapy to prevent high-intensity exercise training-induced increases in oxidative damage, inflammation, skeletal muscle fatigue, and arterial stiffness in elite Taekwondo athletes.

Lactate and Lactate Dehydrogenase in Cistern as Biomarkers of Early Brain Injury and Delayed Cerebral Ischemia of Subarachnoid Hemorrhage

Objective: The pathophysiology of delayed cerebral ischemia (DCI) following aneurysmal subarachnoid hemorrhage (aSAH) has not been fully evaluated. The aim of this study was to evaluate the dynamics of lactate and lactate dehydrogenase (LDH) in carotid cisternal cerebrospinal fluid (CSF), and to discuss their effectiveness as markers of early brain injury (EBI) and DCI following aSAH. Patients and Methods: Among 91 consecutive aSAH patients treated between January 2012 and March 2019 at National Hospital Organization Beppu Medical Center, 19 patients (20.9%) were eligible for this retrospective study. Concentrations of lactate and LDH in carotid cisternal CSF within 14 days after onset of aSAH were evaluated. Results: Six of the 19 patients (31.6%) had a history of DCI. Both lactate and LDH levels in carotid cisternal CSF were significantly higher in the DCI group than in the non-DCI group on postbleeding day (PBD) 1-2, 3-4, and 5-6. Interestingly, neither lactate nor LDH levels in blood differed significantly between DCI and non-DCI groups on PBD 1-2. Conclusions: Lactate and LDH concentrations in carotid cisternal CSF may vividly reflect the EBI and may thus represent predictive biomarkers of DCI following aSAH.

The investigation of the preventive effects of Coenzyme Q10 and Berberine for tourniquet induced ischemia-reperfusion injury on skeletal muscle in rat hindlimb

In this study, the role of CoQ10 and berberine in the treatment of ischemia-reperfusion injury is researched by analyzing the biochemical effects of CoQ10 and berberine administered after experimental ischemia-reperfusion injury in rats. 32 Sprague-Dawley 200-250 g male rats were randomly divided into four equal groups as weighting, including: control, ischemia-reperfusion (I/R) and experimental groups treated with CoQ10 (10 mg/kg dose, 3 times with 8 h intervals) and berberine (200 mg/kg dose, 3 times with 8 h intervals) that were administered by intragastric way to the I/R+ CoQ10 and I/R+ berberine group before two hours ischemia two hours reperfusion with tourniquet. In the sham group, only gastrocnemius muscle were removed and given no CoQ10 and Berberine. By the completion of reperfusion; all rats were anesthetized with ketamine and xylazine, sacrificed after taking samples to measure levels of blood lactate dehydrogenase (LDH), creatine kinase (CK); MDA, MPO, GSH, SOD, GPx and CAT in blood and muscle tissues. Compared to control group, ischemic-reperfusion injury significantly increased plasma LDH, CK; MDA and MPO levels, decreased GSH, SOD, GPx and CAT activities of blood and muscle tissues. Treatments groups showed significantly decreased MDA and MPO levels, increased GSH levels, SOD, GPx and CAT activities compared to the IR group. Our results suggest that CoQ10 and Berberine may protect or treat against oxidative damage on ischemia-reperfusion injury and that can be benefical treating association with lower extremity ischemia-reperfusion injury.

Bone Marrow Tracer Uptake Pattern of PET/CT in Multiple Myeloma: Image Interpretation Criteria and Prognostic Value

The clinical significance of 18F-fluorodeoxyglucose(FDG) positron emission tomography/computed tomography (PET/CT) in the diagnostic approach of multiple myeloma (MM) remains incompletely elicited. Little is known about the value of bone marrow (BM) imaging pattern assessed by PET/CT in MM. And no standardized imaging interpretation criteria have been established to define different imaging pattern. Besides, the lack of standardized interpretation criteria hampered the routine use of PET/CT and led to low interobserver reproducibility in interpreting results. We herein report a study that aimed at finding out the appropriate interpretation criteria to define different tracer uptake pattern on PET/CT and analyzing the prognostic implications of baseline BM FDG uptake pattern in patients with multiple myeloma.We retrospectively studied 52 healthy individuals who had undergone PET/CT scan for cancer screening and 172 newly diagnosed MM patients. In our healthy cohort, BM FDG uptake (represented by the average SUVmean of L1 and L2 vertebral body) were higher than that of liver (SUVmean), spleen (SUVmean) and mediastinal blood pool (SUVmax) in 1 (1.9%), 11 (21.2%) and 4 (7.7%) patients, respectively, in physiological status. Hence, we proposed new PET/CT interpretation criteria for evaluation of BM tracer uptake pattern in MM. According to these criteria, 60 (34.9%) patients had focal (focal lesion in BM with FDG uptake higher than liver, Figure 1A), 6 (3.5%) had diffuse (diffuse homogenous BM FDG uptake higher than liver, Figure 1B), 66 (38.4%) had mixed pattern (innumerable hypermetabolic foci on a background of BM with diffusely increased tracer uptake, Figure 1C) and 40 (23.3%) had normal BM uptake. The bone marrow FDG uptake was correlated to bone marrow plasma cell infiltration rate (r = 0.228, P < 0.01). Besides, plasma cell infiltration rate differed in different uptake pattern: patients with diffuse/mixed bone marrow FDG uptake pattern had the highest mean bone marrow plasma cell infiltration rate, followed by those with focal pattern (Kruskal-Wallis test, P < 0.0001). Furthermore, BM tracer uptake pattern demonstrated correlations with prognostically relevant baseline parameters: diffuse/mixed pattern was correlated with higher BM plasma cell infiltration rate, more advance ISS stage, lower hemoglobin level, higher level of β2-microglobulin and serum creatinine. Diffuse/mixed BM tracer uptake pattern (Figure 2A-B), more than ten FDG-avid focal lesions (PET-FL) at baseline (Figure 2C-D), presence of extramedullary disease (EMD, Figure 2I-J), and a standardized uptake value (SUV-FL) > 5.3 (Figure 2E-F) adversely affected estimated 3-year progression free survival (3-yr PFS; diffuse/mixed pattern: 26.8%; PET-FL > 10: 54.2%; EMD: 0.0%; SUV-FL > 5.3: 32.5%) and overall survival (3-yr OS; diffuse/mixed pattern: 50.6%; PET-FL > 10: 44.8%; EMD: 0.0%; SUV-FL > 5.3: 51.0%). Presence of paramedullary soft tissue lesion adjacent to bone marrow shortened PFS with borderline adverse influence on OS (Figure 2K-L). Clinical outcomes were not significantly influenced by the number of osteolytic lesion on CT images (Figure 2G-H). In multivariate analysis (Table 1), the following factors were found to be independent prognostic factors for inferior outcome: diffuse/mixed BM uptake pattern, PET-FL > 10, EMD, hypercalcemia, hypoalbuminemia and level of blood lactate dehydrogenase > upper limit. Diffuse/mixed BM FDG uptake pattern was an independent predictor associated with inferior OS (HR 7.10; 95% CI 1.33-37.95) and PFS (HR 5.98; 95% CI 1.30-27.54).In conclusion, we propose an FDG uptake higher than that of liver is an appropriate positivity cut-off to discriminate physiological and pathological uptake in bone marrow for patients with multiple myeloma. With these interpretation criteria, the bone marrow PET/CT pattern can be defined as four types: normal, focal, diffuse and mixed. A diffuse/mixed BM FDG uptake pattern is a reliable predictor of inferior outcome. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Creatine Kinase and Lactate Dehydrogenase Responses after Different Resistance and Aerobic Exercise Protocols.

The aim of this study was to investigate the responses of creatine kinase (CK) and lactate dehydrogenase (LDH) after performing different resistance and aerobic exercise protocols. Twelve recreationally trained men (age, 23.2 ± 5.6 years; body mass, 84.3 ± 9.3 kg; body height, 178.9 ± 4.5 cm; and BMI, 26.3 ± 2.3 kg·m2) volunteered to participate in this study. All subjects were randomly assigned to four experimental protocols (crossover): (a) aerobic training at 60% of VO2max, (b) aerobic training at 80% of VO2max, (c) a resistance exercise (RE) session with a bi-set protocol, and (d) an RE session with a multiple sets protocol. Blood samples were collected before, immediately after and 24 hours following the experimental protocols. After 24 hours, there was a significant increase in CK for the 80% of VO2max protocol vs. the bi-set RE session (p = 0.016). Immediately after the protocols, we observed a significant increase in LDH among certain groups compared to others, as follows: multiple sets RE session vs. 60% of VO2max, bi-set RE session vs. 60% of VO2max, multiple sets RE session vs. 80% of VO2max, and bi-set RE session vs. 80% of VO2max (p = 0.008, p = 0.013; p = 0.002, p = 0.004, respectively). In conclusion, aerobic exercise performed at 80% of VO2max appears to elevate plasma CK levels more than bi-set RE sessions. However, the bi-set and multiple sets RE sessions appeared to trigger greater levels of blood LDH compared to aerobic protocols performed at 60% and 80% of VO2max.

Clinical and Laboratory Fectures Of T-Cell Prolymphocytic Leukemia In China

ObjectiveTo investigate the clinical and laboratory characteristics and survival of Chinese patients with T-cell prolymphocytic leukemia (T-PLL). MethodEleven patients with T-PLL were retrospectively analysed. ResultThere were nine males and two females, with the median age of 56.0(19-69) years old. All the patients, except for three, presented with leukocytosis. Marked leukocytosis was less frequent than that in the British series (75%) (P = 0.00). It was easy to see PB lymphocytosis with the median ALC of 17.22(0.58-148.83) ×109/L. Lymphadenopathy and splenomegaly were the most common physical finding. It was common that serum lactate dehydrogenase (LDH) and beta 2 microglobulin (β2-MG) were higher than normal. All cases were positive for CD2/ CD3/ CD5/TCRαβand negative for CD1a /HLA-DR and TdT, as for surface markers, including strong expression of CD7. By chromosome analyses, most cases (9/10)have normal chromosome .This rate is significantly higher than that of the British and American series (3% and 25%) (P =0.000, P =0.001). And 14q11 abnormality and trisomy 8q, which are common among Western cases, were not observed in any cases. With a median follow-up of 23 months, three cases died. Two year progress free survival (PFS) and overall survival (OS) were 53.3% and 50% , respectively. However, whether three cases with normal cytogenetics and indolent clinical courses could regard as “T-CLL” is needs to be investigated in future studies. ConclusionIt was common that the increased lymphocyte count and lymphadenopathy as well as splenomegaly with T-PLL. And most cases have high level of blood LDH and β2-MG and normal chromosome karyotype. Of great interest is similar features are observed in cases in other East Asian countries such as Japan. Genome-wide analyses such as high-throughput mutation profiling, previously performed in other T-cell malignancies, will clarify the differences between Western cases and East cases in the future. Disclosures:No relevant conflicts of interest to declare.

Amylopectin is the anti-fatigue ingredient in glutinous rice

The anti-fatigue activities of glutinous rice (GR) and GR amylopectin (GRA) were investigated in mice by determining tissue glycogen, blood lactate dehydrogenase (LDH), and blood urea nitrogen (BUN) after the weight loaded forced swim test (WFST). GR and GRA were given by gavage at various doses of GR (7.5, 15, 30g/kg body weight) and GRA (3.8, 7.5, 15g/kg body weight) every day for 7 days, respectively. The results indicated that the hepatic glycogen levels significantly (P<0.05) increased 26–44% and 35–60% and the muscle glycogen levels significantly (P<0.05) increased 36–100% and 67–133% in GR and GRA treatment groups, compared with the negative control group. The GRA treatment groups also had significantly (P<0.05) higher (9.1–20.3%) blood LDH levels. Meanwhile, the blood LDH activities in GR and GRA treatment groups had a significantly positive correlation with the hepatic glycogen levels (r=0.978, P<0.01). Moreover, except of the low-dose GR (7.5g/kg body weight) supplemented group, mice in all other treatment groups had significantly (P<0.05) lower (13–23%) BUN levels. Compared with the GR treatment groups, GRA treatment groups had similar or even higher anti-fatigue activities, which demonstrated that GRA might play the most important role on the anti-fatigue activities for GR.

Clinical and laboratory features of T-cell prolymphocytic leukemia in China

To investigate the clinical and laboratory characteristics and survival of Chinese patients with T- cell prolymphocytic leukemia (T-PLL). Eleven patients with T-PLL admitted in our hospital from Jan 2006 to Oct 2012 were retrospectively analyzed. Of the 11 patients, nine were males and two females, with the median age of 56.0(19-69) years old. All the patients, except for three, presented with leukocytosis. The incidence of hyperleukocytosis (1/11) was less frequent than that in the British series (75%) (P=0.000). Lymphocyte counts in peripheral blood were increased in 9 of the 11 patients with the median absolute lymphocyte count (ALC) of 17.22(0.58-148.83)×10⁹/L. Superficial lymphadenopathy and splenomegaly were the most common physical signs. It was common that serum lactate dehydrogenase (LDH) and beta 2 microglobulin(β2-MG)were higher than normal level. All cases were positive for CD2/CD3/CD5/TCRαβ, negative for CD1a /HLA-DR and TdT, and most of them were strong positive for CD7 expression. By chromosome analyses, most cases. (9/10) have normal chromosome. This rate is significantly higher than that of the British and American series (3% and 25%, respectively) (P=0.000, P=0.001). The 14q11 abnormality and trisomy 8q, which are common among Western cases, were not observed in any of our cases. With a median follow-up of 23.0 months, three patients died. Two year progress free survival (PFS) and overall survival (OS) were 53.3% and 50%, respectively. There were 3 patients with PFS over a number of years, whether it should be considered as the T-chronic lymphocytic leukemia (T-CLL) is worthy of further studies. The common clinical manifestations of T-PLL patients were increased lymphocyte counts and lymphadenopathy as well as splenomegaly. And most cases have high level of blood LDH and β2- MG and normal chromosome karyotype.

Magnesium lithospermate B protects cardiomyocytes from ischemic injury via inhibition of TAB1-p38 apoptosis signaling

Danshen has been used in traditional Chinese medicine for hundreds of years to treat cardiovascular diseases. However, its precise cardioprotective components and the underlying mechanism are still unclear. In the present study, we demonstrated that in a rat model of acute myocardial infarction, the treatment with magnesium lithospermate B (MLB), the representative component of phenolic acids in Danshen, significantly reduced the infarct size and the blood lactate dehydrogenase level. In contrast, tanshinone IIA, the representative component of lipophilic tanshinones in Danshen, had no such protective effects. Moreover, in the simulated ischemia cell model, MLB treatment considerably increased the cell viability and reduced the sub-G1 population and the apoptotic nuclei, indicating its anti-apoptotic effect. Further mechanism study revealed that the ischemia-induced p38 phosphorylation was abolished by MLB treatment. Interestingly, MLB specifically inhibited the TGFβ-activated protein kinase 1-binding protein 1 (TAB1) mediated p38 phosphorylation through disrupting the interaction between TAB1 and p38, but it did not affect the mitogen-activated protein kinase 3/6 mediated p38 phosphorylation. In conclusion, the present study identifies MLB as an active component of Danshen in protecting cardiomyocytes from ischemic injury through specific inhibition of TAB1–p38 apoptosis signaling. These results indicate TAB1–p38 interaction as a putative drug target in treating ischemic heart diseases.

Analysis of C-Reactive Protein and Biochemical Parameters in Pericardial Fluid

This study was designed to examine the relationship between pericardial fluid and plasma CRP levels, and to alterations in other biochemical parameters in patients undergoing Coronary Artery Bypass Grafting (CABG). The study group consisted of 96 Coronary Artery Disease (CAD) patients who were referred to our clinic for a CABG procedure and from whom sufficient amount of pericardial fluid could be collected. The patients were classified into 3 groups: Stable Angina Pectoris (SAP) (n = 27), Unstable Angina Pectoris (USAP) (n = 36), and Post-Myocardial Infarction (PMI) (n = 33). Levels of CRP, glucose, albumin, total protein, Creatine Kinase (CK), Creatine Kinase-MB (CK-MB), and Lactate Dehydrogenase (LDH) were determined in pericardial fluid samples and in simultaneously collected blood samples from radial artery. The pericardial CRP and LDH levels in the PMI group were higher than in the SAP (p = 0.015 and p = 0.000, respectively) and USAP (p = 0.011, p = 0.047) groups. Serum CRP levels in USAP (p = 0.014) and PMI (p = 0.000) groups were higher than those in the SAP group. Pericardial albumin levels in the PMI group were higher than in the USAP group (p = 0.038). In all groups, the pericardial fluid/serum protein ratio was > 0.5, the LDL ratio was > 0.6, and pericardial fluid LDH concentrations were > 300 mg/dl. CRP level of pericardial fluid was significantly higher in the PMI group than in other groups. However, pericardial fluid LDH levels were higher than blood LDH levels in this group and were also higher than pericardial fluid LDH levels of other groups.