Total Lactate Dehydrogenase Research Articles

Tanshinone IIA attenuates paraquat‑induced acute lung injury by modulating angiotensin‑converting enzyme 2/angiotensin‑(1‑7) in rats.

Tanshinone IIA (TIIA) is an active compound that can be isolated from the Chinese herb, Salviamiltiorrhizae Bunge, also known as danshen. Previous studies have demonstrated that TIIA can effectively attenuate bleomycin‑induced pulmonary fibrosis in rats. However, it has not been determined whether TIIA can attenuate paraquat (PQ)‑induced acute lung injury (ALI). In the present study, the protective effects exhibited by TIIA on PQ‑induced ALI, as well as its underlying mechanisms, were investigated using Sprague‑Dawley (SD) rats. ALI animal models using rats were established via administration of PQ. Adult male SD rats were randomly divided into three groups: A control group, a PQ group and a PQ+TIIA group. Total cell count, total protein levels and lactic dehydrogenase (LDH) levels in bronchoalveolar lavage fluid (BALF), as well as myeloperoxidase (MPO) activity in lung tissues were determined. Lung histological alterations were also investigated. Angiotensin converting enzyme 2 (ACE2) and Angiotensin1‑7 [Ang‑(1‑7)] expression levels in the lung were also analyzed. The results demonstrated that administration of PQ induced marked histological alterations, and markedly increased neutrophil infiltration, lung wet/dry weight ratio, total cell count, protein content and LDH levels in BALF. In addition, PQ was revealed to significantly decrease ACE2 and Ang‑(1‑7) expression levels in lung tissues. However, it was demonstrated that TIIA attenuated these effects. Therefore, the results of the present study suggest that that TIIA may exhibit a therapeutic effect regarding PQ‑induced ALI in rats, and that ACE2 and Ang‑(1‑7) may be involved in the underlying mechanisms of this effect.

Monitoring of pre-competition dehydration- induced skeletal muscle damage and inflammation levels among elite wrestlers.

Weight loss practice before competitions is a common method in weight sports. The current study aimed to monitor Plasma Osmolarity (POsm), skeletal muscle damage and inflammation levels induced by pre-competition dehydration among elite wrestlers. Twenty-four male elite wrestlers participated in the study. A survey information form that assessed pre-competition weight loss practices were administered to the wrestlers. Additionally, Total Creatine Kinase (CK), Lactate Dehydrogenase (LDH), Aspartate Aminotransferase (AST), Alanine Aminotransferase (ALT), C-reactive Protein (C-RP) and POsm, analyses were evaluated by a specialist at the biochemical laboratory. POsm level for euhydration is ⩽ 290 mOsm/L. But if POsm level is > 290, then dehydration occurs. The wrestlers were divided into two groups according to POsm levels as weight loss and non-weight loss group. There were differences in the pre and post-test POsm levels of weight loss group. Similarly; it was identified that there were also statistically significant differences in terms of ALT, LDH and CK levels of weight loss group between pre and post-test. It was seen that POsm and levels of all indicators of skeletal muscle damage were higher than non-weight loss group. However, it was found that there were not any differences in terms of C-RP levels.

Plasma cell‐free DNA quantification is highly correlated to tumor burden in children with neuroblastoma

To evaluate plasma cell‐free DNA (cfDNA) as a promising biomarker for neuroblastoma (NB) tumor burden. Seventy‐nine eligible patients with newly diagnosed NB were recruited from Beijing Children's Hospital between April 2016 and April 2017. Additionally, from September 2011 to June 2017, 79 patients with stable NB were evaluated with a median follow‐up time of 21 months. Approximately 2 mL of peripheral blood was drawn upon enrollment, and plasma cfDNA levels were measured via quantitative polymerase chain reaction (qPCR). Total cfDNA analysis was performed using the long interspersed nuclear element 1 (LINE‐1) 79 bp fragment, and DNA integrity was calculated by the ratio of the LINE‐1 300 bp fragment to the LINE‐1 79 bp fragment. A total of 79 NB patients with a median age of 36 months comprised the group of newly diagnosed NB patients. The main primary tumor site was the retroperitoneal and adrenal region (81%). Three or more metastatic sites were found in 17.7% of patients. Stable NB patients older than 18 months comprised 98.7% of the stable NB patients. Neuron‐specific enolase (NSE), lactate dehydrogenase (LDH), and cfDNA levels were dramatically increased in the newly diagnosed NB patients and significantly different from those in the stable NB patients. Moreover, the concentration of cfDNA was much higher in patients with larger tumors. By analyzing the area under the receiver operator characteristic (ROC) curve (AUC), the areas of total cfDNA, NSE, and LDH levels were 0.953, 0.929, and 0.906, respectively. The sensitivity and specificity data clarified that the level of circulating cfDNA in plasma can be considered as a reliable biomarker for describing tumor load in NB. The plasma cfDNA concentration was as good as the levels of LDH and NSE to discriminate the tumor burden in children with NB.

The Antioxidant Status and Biochemical Parameters in Kid Goats Naturally Infected with Peste Des Petits Ruminants Virus

Background: Peste des petits ruminants (PPR) is an acute and highly contagious viral disease of small ruminants. The disease is high economical importance because of the high mortality rate. Oxidative stress is an active field of research in small ruminant medicine and has been implicated in numerous disease processes including sepsis, mastitis, acidosis, enteritis, pneumonia, respiratory, and joint diseases. Compared to human medicine, only a limited number of conditions have been investigated in regard to the effects of oxidative stress in small ruminants. The aim of this study was to determined and compared the oxidative status and some biochemical parameters in kid goats with PPR.Materials, Methods & Results: The study was performed on 15 healthy hair of kid goats (control group) and 15 kids naturally infected with Peste des Petits Ruminants (PPR). Competitive enzyme linked immunosorbent assay (C-ELISA) was used for serological detection of PPRV specific antibodies, and a reverse transcription polymerase chain reaction (RT-PCR) was performed for the detection of PPR virus. Concentrations of plasma biochemical parameters were analysed by a clinical chemistry analyser, and blood biochemical indices determined, including total protein, albumin, alkaline phosphatase (ALP), aspartate amino transferase (AST), γ- glutamyl transferase (GGT), lactate dehydrogenase (LDH), glucose, very low density lipoprotein (VLDL), low density lipoprotein (LDL), high density lipoprotein (HDL). The plasma CAT activity, plasma GSHPx activity and plasma lipid peroxidation level was measured according to the specific methods. Besides, vitamin C values were colorimetrically determined using a phosphotungustic method acid method and vitamin E values were determined spectrophotometrically method. Plasma MDA concentrations were markedly increased in the group of kid goats with PPR (P < 0.001) whereas GSHPx (P < 0.01), and CAT (P < 0.01) activities were significantly depressed as well as concentrations of vitamins E (P < 0.05) and vitamin C (P < 0.001). Significant differences between groups were showed relative to plasma total protein (P < 0.05), albumin (P < 0.05), ALP (P < 0.05), AST (P < 0.01), GGT (P < 0.05), LDH (P < 0.05), glucose (P < 0.001), VLDL (P < 0.05), LDL (P < 0.01), and HDL (P < 0.05)Discussion: The clinical and postmortem findings of PPRV infection may be sufficient for the diagnosis in the endemic areas, yet labaratory confirmation is essential for definitive diagnosis because of the clinical similarity of PPR to rinderpest. In this study used both C-ELISA and RT-PCR in the diagnosis of suspected disease. The decrease level of VLDL, LDL, and HDL in the kids with PPR were consistent findings with liver damage, and the cause of decrease could be inadequate synthesis of cholesterol that main structure of lipoproteins due to liver dysfunction. Plasma MDA concentrations were found to be increased in the kid goats with PPR compared to the control group, while decreases of GSHPx and CAT activities were observed. Because of GSHPx and CAT are involved in the conversion of radicals into less effective metabolites, these changes coupled to the increase of MDA concentrations, suggest that an excessive ROS production occurred during PPR infection. This study has highlighted the occurrence of an oxidative stress with important differences in antioxidant status as reflected by assessment of some enzymatic and non-enzymatic antioxidants in kids infected by PPRV. In conclusion, this study has highlighted the occurrence of an oxidative stress with important differences in antioxidant status as reflected by assessment of some enzymatic and non-enzymatic antioxidants in kids infected by PPRV. Furthermore, the liver was effected by PPRV infection.

Influence of biological factors on hematological and serum biochemistry values in captive Adélie, Chinstrap, Gentoo, and Macaroni penguins in Pingtung, Taiwan.

Hematology and serum biochemistry reference values are essential for health evaluation and disease diagnosis in penguins. However, there are currently no published physiological values for captive Adélie (Pygoscelis adeliae) and Chinstrap penguins (P. antarcticus), nor for wild or captive Macaroni penguins (Eudyptes chrysolophus). The present study is the first investigation regarding hematology and serum biochemistry reference values for captive Adélie, Gentoo (P. papua), Chinstrap, and Macaroni penguins in Asia. Fixed effect models for repeated measure were applied to determine the influence of penguin species, age, gender, and age-gender interaction on each blood parameter. Hematology and serum biochemical data from 122 apparently healthy penguins (24 Adélie, 38 Chinstrap, 46 Gentoo, and 14 Macaroni) were collected between 2009 and 2014. The effects of penguin species were observed for most blood parameters, except total bilirubin, creatine kinase (CK), creatinine, and potassium ion (K+ ). Values of mean corpuscular volume, mean corpuscular hemoglobin (MCH), heterophil, ratio of heterophils to lymphocytes (H/L), alanine aminotransferase (ALT), and chloride ion (Cl- ) had significant positive correlation with age, while significant negative correlation with age was observed in total red blood cells (RBCs), lymphocytes, thrombocytes, alkaline phosphatase (ALP), CK, lactate dehydrogenase (LDH), and plasma iron. Compared to male penguins, females had lower mean corpuscular hemoglobin concentration (MCHC) and blood urea nitrogen (BUN) but higher calcium ion (Ca2+ ) values. As for age-gender interaction, significant positive correlation was shown in MCHC and K+ , and the reverse was true in H/L ratio.

SPECIES- AND AGE-SPECIFIC CHARACTERISTICS OF THE LACTATE DEHYDROGENASE SYSTEM IN TISSUES OF RODENTS (MAMMALIA: RODENTIA)

The aim of this study was to analyze the species-specific features and age-related changes in the total lactate dehydrogenase activity (LDh, EC 1.1.1.27) and LDh patterns in some tissues in three species of rodents (Rodentia) with different ecological characteristics – the northern birch mouse Sicista betulina (Pallas, 1779), the European water vole Arvicola amphibius (L., 1758) and the tundra vole Microtus oeconomus (Pallas, 1776). Compared to the European water vole and the northern birch mouse, the tundra vole had a higher content of M-subunits and the amount of LDh-5 isoenzyme in the liver and skeletal muscles, higher contents of aerobic LDh-1 isoenzymes and, respectively, of h-subunits in kidneys and heart. In the heart and kidneys, the hybrid fractions (LDh-2, LDh-3, LDh-4) dominated over LDh-1 and LDh-5 in the northern birch mouse. The total LDh activity in the liver and kidneys of the northern birch mouse was higher than in the tundra vole. The extent of anaerobic ATP production in the liver of small rodents varied – the liver of the diving European water vole contained more LDh-2, LDh- 3, LDh-4 and h-subunits than the corresponding tissue in the non-diving tundra vole. In kidneys of the northern birch mouse and European water vole, the content of the LDh- 5 isoenzyme increased through the ontogeny. The LDh activity was higher in the heart of European water vole adults compared to young animals. Species-specific differences in LDh isoenzyme spectra and total LDh activity in the studied mammals reflect their adaptation to the semi-aquatic and hibernating lifestyles.

Cerebrospinal Fluid Lactic Dehydrogenase Activity in Children with Acute Lymphoblastic Leukemia Treated for Cranial Prophylaxis

Total lactic dehydrogenase (TLDH) activity in cerebrospinal fluid (CSF) has been prospectively studied in order to determine whether it could be a biochemical marker for brain damage due to cranial prophylaxis in children with acute lymphoblastic leukemia (ALL). TLDH activity has been measured in 15 patients before prophylaxis, in 15 patients after the prophylaxis which consisted of cranial radiotherapy (2400 rads) and intrathecal methotrexate (0.5 mg/kg-dose, 5 doses), in 8 patients after radiotherapy alone (2400 rads) and in 9 patients after intrathecal methotrexate (0.5 mg/kg-dose, 5 doses) alone. TLDH activity in CSF of combined prophylaxis group has been found to be higher than the ones before study (p less than 0.05). There were insignificant elevations of TLDH activity in the other two groups (p greater than 0.05; p greater than 0.05). This result indicated combined cranial prophylaxis seemed to be more toxic than the other prophylaxis regimens when they were used alone.

Reference intervals for the activity of lactate dehydrogenase and its isoenzymes in the serum and cerebrospinal fluid of healthy canines

Lactate dehydrogenase (LD) exists as 5 isoenzymes (LD-1 through LD-5) that are expressed throughout the body and can be detected in both serum and cerebrospinal fluid (CSF). LD and its isoenzymes have been relatively unstudied in veterinary medicine, although studies in human medicine have demonstrated that changes in total LD activity and atypical isoenzyme patterns can indicate disease processes, including neurologic abnormalities. The purpose of this study was to establish RIs for LD and its isoenzymes in the serum and CSF of clinically healthy dogs. By establishing a definitive RI for this enzyme in healthy canines, further study of the clinical and diagnostic usefulness of LD can be undertaken. Serum and atlantoaxial CSF were collected from clinically healthy dogs. Total LD activity was measured spectrophotometrically immediately after collection. Isoenzyme distributions were also determined within 8hours of collection using the QuickGel LD Isoenzyme technique and a densitometric scanner. The median serum total LD in healthy canines was 69.0 U/L (n=41; range: 21.0-217.0U/L), while the median CSF total LD was 10.0 U/L (n=40; range: 6.0-19.3U/L). LD-5 is the predominant isoenzyme in canine serum (n=40), contributing over half of the total enzyme activity. Conversely, in canine CSF (n=42), LD-1 is the predominant isoenzyme, followed by LD-2 and LD-3. Knowledge of the distribution and concentration of LD in the serum and CSF of healthy dogs will set the foundation for future studies of canine LD as a potentially clinically useful biomarker.

Potentiation of Sodium Metabisulfite Toxicity by Propylene Glycol in Both in Vitro and in Vivo Systems.

Many consumer products used in our daily lives result in inhalation exposure to a variety of chemicals, although the toxicities of the active ingredients are not well known; furthermore, simultaneous exposure to chemical mixtures occurs. Sodium metabisulfite (SM) and propylene glycol (PG) are used in a variety of products. Both the cytotoxicity and the sub-acute inhalation toxicity of each chemical and their mixtures were evaluated. Assays for cell viability, membrane damage, and lysosome damage demonstrated that SM over 100 μg/ml induced significant cytotoxicity; moreover, when PG, which was not cytotoxic, was mixed with SM, the cytotoxicity of the mixture was enhanced. Solutions of 1, 5, and 20% SM, each with 1% PG solution, were prepared, and the whole body of rats was exposed to aerosols of the mixture for 6 h/day, 5 days/week for 2 weeks. The rats were sacrificed 1 (exposure group) or 7 days (recovery group) after termination of the exposure. The actual concentration of SM in the low-, medium-, and high-exposure groups was 3.91 ± 1.26, 35.73 ± 6.01, and 80.98 ± 5.47 mg/m3, respectively, and the actual concentration of PG in each group was 6.47 ± 1.25, 8.68 ± 0.6, and 8.84 ± 1.77 mg/m3. The repeated exposure to SM and PG caused specific clinical signs including nasal sound, sneeze, and eye irritation which were not found in SM single exposure. In addition, the body weight of treatment group rats decreased compared to that of the control group rats in a time-dependent manner. The total protein concentration and lactate dehydrogenase activity in the bronchoalveolar lavage fluid (BALF) increased. Histopathological analysis of the lungs, liver, and nasal cavity was performed. Adverse effects were observed in the nasal cavity, with squamous cell metaplasia identified in the front of the nasal cavity in all high-exposure groups, which completely recovered 7 days after exposure was terminated. Whereas inhalation of SM for 2 weeks only reduced body weight in the high-dose group, inhalation of SM and PG mixtures for 2 weeks significantly decreased body weight and induced metaplasia of the respiratory epithelium into squamous cells in the medium- and high-dose groups. In conclusion, PG potentiated the toxicity of SM in human lung epithelial cells and the inhalation toxicity in rats.

Melatonin provides protection against heat stroke-induced myocardial injury in male rats.

This study aimed to investigate the cardioprotective effects of melatonin on heat stroke (HS) induced acute myocardial infarction in rats and to explore the underlying mechanisms. Myocardial injury was induced by subjecting the anaesthetized rats to a high ambient temperature of 43°C for 70 min. Such a high ambient temperature caused hyperthermia, hypotension and myocardial injury in rats. Rats were treated with melatonin (3 mg/kg) intravenously one hour before and followed by an additional dose immediately after heat stress. At the onset of HS, animals displayed myocardial injury evidenced by increased levels of cardiac damage indicators (e.g. total lactate dehydrogenase, cardiac troponin I and creatine kinase-MB), increased cardiac damage scores and suppressed left ventricular performance. Animals with HS also had increased cardiac oxidative stress evidenced by increased levels of lipid peroxidation (e.g. increased thiobarbituric acid reactive substances) and decreased levels of antioxidant enzymes (e.g. superoxide dismutase, catalase and reduced glutathione) and activated inflammation (e.g. increased levels of interleukin-6 and tumour necrosis factor-α). Pretreatment with melatonin significantly reversed the HS-induced myocardial injury, cardiac oxidative stress and cardiac inflammation. Melatonin may protect against HS-induced myocardial injury in male rats by mitigating oxidative stress and inflammation.

Role of ethanolic extract of Morus alba leaves on some biochemical and hematological alterations in irradiated male rats

Purpose: The present study aimed to evaluate the protective role of “Morus alba Linn (Family: Moraceae) commonly known as mulberry” leaves extract against hazardous effects of gamma rays in male rats.Materials and methods: Thirty six male albino rats were divided into six groups (six rats/group); (1) control group received 1 ml distilled water, (2) low dose of extract (100 mg/kg) group treated daily with low oral dose of ethanolic extract of mulberry leaves (100 mg/kg body weight (b.wt.)) for 21 consecutive days, (3) high dose of extract (200 mg/kg) group treated daily with high oral dose of ethanolic extract of mulberry leaves (200 mg/kg b.wt.) for the same period, (4) irradiated group rats were subjected to whole body gamma irradiation at a shot dose of 7 Gy, (5) low dose of extract + irradiated group treated daily with low oral dose of ethanolic extract of mulberry leaves (100 mg/kg b.wt.) for 21 consecutive days then rats were exposed to gamma irradiation at a single dose of 7 Gy, (6) high dose of extract + irradiation group treated daily with high oral dose of ethanolic extract of mulberry leaves (200 mg/kg b.wt.) for 21 consecutive days then rats were exposed to gamma irradiation at a single dose of 7 Gy. Rats were sacrificed 1, 7, 15 days post gamma irradiation in all groups. Blood samples were taken at three intervals time in the six groups.Results: The results showed that whole body irradiation of rats induced significant decrease (p < 0.05) in red blood cells (RBCs), hemoglobin (Hb), hematocrit percentage (HCT%), platelet, white blood cells (WBCs), lymphocytes, neutrophils, serum glucose-6-phosphate dehydrogenase (G-6-PD) and insulin. The data also showed significant increase (p < 0.05) in serum total lipids, phospholipids, cholesterol, triglycerides, lactate dehydrogenase (LDH), creatine kinase (CK), and plasma glucose. Administration of mulberry leaves extract, either low or high concentrations to rats prior to irradiation caused significant improvement in the studied parameters.Conclusions: Mulberry leaves extract prior to exposure to gamma irradiation has radio protector against hazardous effect of irradiation in male rats.

Evaluasi Keselamatan Lactobacillus casei C1 pada Tikus Wistar

Nowadays, probiotics have been widely consumed as supplementary food for their health benefits. However, safety evaluation for many probiotic bacteria is still lacking. Furthermore, health benefits conferred by probiotics depend on the strains used in producing probiotic products. Therefore, it is important to examine oral toxicity of newly isolated Lactobacillus casei (Lb. casei) C1. A total of 32 Wistar (WIS) rats were divided into acute (single dose) and subacute oral toxicity (28-days repeated dose) groups. Rats in each group were further divided into control group which received phosphate buffer saline (PBS) orally and treatment group that was administered orally with Lb. casei C1 (10 11 CFU/ml). For acute oral toxicity, treatment was performed on day-1 and the effects were monitored subsequently for 14 days. For subacute oral toxicity, treatment was given daily for 28 days and the effects were observed throughout the experimental period. Body weight, food and water intake of the rats were recorded. Rats in acute and subscute groups were sacrificed on day-15and day-29, respectively. Serum was collected to determine the levels of total protein, malondialdehyde (MDA), alanine transaminase (ALT), aspartate transaminase (AST), lactate dehydrogenase (LDH) and creatinine. Organs were also harvested for histological examination. There were no significant differences (p>0.05) in body weight, food and water intake between the control and treated rats in acute oral toxicity group. There were also no significant differences in the blood cell count, levels of total protein, MDA, LDH and creatinine between the control and treated rats. Similar findings were recorded for the subacute oral toxicity group, except that the levels of ALT and AST which were significantly different (p<0.05). When observed under a light microscope, there were no morphological changes detected in the kidney, liver and ileum of treated rats as compared to control rats in both of the experimental groups. In conclusion, Lb. casei C1 exhibited no toxic effects in Wistar rats hence safe to be consumed orally. DOI : http://dx.doi.org./10.17576/JSKM-2018-1602-04

Correlation of serum lactate dehydrogenase and alkaline phosphatase in different histological grades of head and neck squamous cell carcinoma and premalignant lesions.

Head neck cancer (HNCA) in North-East India accounts for 54.48% cancers at all sites, one of the highest in the country. Increased serum lactate dehydrogenase (LDH) activity is considered as a marker of cellular necrosis while serum alkaline phosphatase (ALP) is recognized as an important marker of induction of tumor cell differentiation. Considering the importance and need of biomarker in HNCA and there being no previous study on tumor markers from this highly prevalent region, we intended to examine the role of serum LDH and ALP in head and neck squamous cell carcinoma (HNSCC) and epithelial precursor lesions (EPLs) and also to find their correlation with the different histological grades of tumor. This is a prospective observational study on patients with HNSCC and precancerous lesions attending Department of ENT of a Teaching Hospital. Serum LDH and ALP was measured in HNSCC, EPL and control groups and the results were statistically analyzed and compared using analysis of variance, Pearson correlation coefficient, and sensitivity-specificity analysis. Serum LDH was found to be a significant marker of HNSCC. Total serum LDH level was high in both premalignant and HNSCC cases. There was a significant correlation between serum LDH and grades of HNSCC showing highest levels of expression in moderately differentiated SCC. Elevated serum LDH was also seen in erythroleukoplakia, leukoplakia, and verrucous lesion, but serum ALP levels were not significant. This is the first study from this highly prevalent region of HNCA showing that serum LDH could be regarded as a biomarker for malignant and premalignant conditions of the head and neck.

Serum lactate dehydrogenase isoenzymes 4 plus 5 is a better biomarker than total lactate dehydrogenase for refractory Mycoplasma pneumoniae pneumonia in children

Although usually self-limiting, Mycoplasma pneumoniae pneumonia (MPP) may lead to clinical or radiological deterioration despite macrolide antibiotic therapy, resulting in the development of refractory MPP (RMPP). Corticosteroids have been used to treat RMPP with beneficial effects. Serum lactate dehydrogenase (LDH) is a suggested biomarker for the use of steroid therapy. Since serum LDH is a non-specific marker and elevated in many inflammatory processes, this study investigates the predicting level of LDH isoenzymes for RMPP. Fifty-four children with non-refractory M. pneumoniae pneumonia (NRMPP) and 16 children with RMPP were enrolled in this study. In comparison to the NRMPP group, the RMPP group showed significantly higher levels of serum LDH. Concerning LDH isoenzymes, the RMPP group showed significantly lower proportions of LDH1 and LDH2, while higher LDH4 and LDH5 percentage. Receiver operating characteristic curve analysis showed that the area under the curve for the total LDH data was 0.812 with a cut-off of 408IU/L (sensitivity of 75.0%, specificity of 72.2%). The areas under the curve for LDH4, LDH5, and [LDH4+LDH5] were estimated to be 0.813, 0.818, and 0.829, respectively. The threshold for [LDH4+LDH5] was estimated to be 109.4IU/L (sensitivity, 75.0%; specificity, 87.0%). These results indicate that for the initiation of corticosteroid therapy, serum [LDH4+LDH5] level is a more sensitive biomarker than total LDH.

Sensitive skin is highly frequent in extrinsic atopic dermatitis and correlates with disease severity markers but not necessarily with skin barrier impairment

BackgroundSensitive skin is a condition of cutaneous hypersensitivity to environmental factors. Lactic acid stinging test (LAST) is commonly used to assess sensitive skin and composed of four distinct sensations (pain, burning sensation, itch, and crawly feeling). A link between sensitive skin and barrier dysfunction has been proposed in atopic dermatitis (AD) patients. However, clinical and laboratory factors that are associated with sensitive skin remain unelucidated. ObjectiveTo investigate relationship between sensitive skin and AD-associated markers. MethodsForty-two Japanese AD patients and 10 healthy subjects (HS) were enrolled. AD patients were divided into extrinsic (EAD; high IgE levels) and intrinsic (IAD; normal IgE levels) types. We conducted 1% LAST by assessing the four distinct sensations and calculated the frequencies of sensitive skin in EAD, IAD, and HS. We also performed clinical AD-related tests, including transepidermal water loss (TEWL), visual analogue scale (VAS) of pruritus, and quality of life, and measured laboratory markers, including blood levels of IgE, CCL17/TARC, lactate dehydrogenase (LDH) and eosinophil counts, and concentration levels of serum Th1/Th2 cytokines. Filaggrin (FLG) mutations were examined in 21 patients. These values were subjected to correlation analyses with each of the four sensation elements. ResultsAccording to the standard criteria for LAST positivity, the frequencies of LAST-positive subjects were 54.8% and 10.0% in AD and HS, respectively (P=0.014). EAD patients showed a significantly (P=0.026) higher frequency of positive LAST (65.6%) than did IAD patients (20.0%). Among the four LAST sensation elements, the crawly feeling and pain scores positively correlated with VAS of pruritus, total serum IgE, mite-specific IgE, CCL17/TARC, and/or LDH. There was no association of the LAST scores with serum Th1/Th2 cytokine levels. Notably, neither TEWL nor FLG mutations correlated with LAST positivity or any sensation scores. ConclusionsThe frequency of sensitive skin is higher in EAD than in IAD. Sensitive skin is associated with AD severity, but not necessarily with barrier condition.

Epithelial Deletion of Sulf2 Exacerbates Bleomycin-Induced Lung Injury, Inflammation, and Mortality.

Epithelial injury has been proposed to be the initiating factor in the pathogenesis of idiopathic pulmonary fibrosis (IPF). We have shown previously that heparan sulfate 6-O-endosulfatase (Sulf) 2 is overexpressed in the hyperplastic type II alveolar epithelial cells (AECs) in the IPF lungs. By removing 6-O-sulfates from specific heparan sulfate intrachain sites, Sulf2 modulates the functions of many growth factors and cytokines. In this study, we hypothesized that Sulf2 plays a regulatory role in alveolar epithelial injury and repair, using the murine bleomycin model. Consistent with our findings in human IPF lungs, bleomycin treatment in mice resulted in up-regulation of Sulf2 mRNA in whole-lung extracts and overexpression of Sulf2 protein in type II AECs on lung tissue sections. Sulf2 protein was detectable in bronchoalveolar lavage fluid at baseline, and its level was significantly increased after bleomycin exposure. To study the role of Sulf2 in alveolar injury and repair in vivo, we generated a doxycycline-inducible epithelial-specific Sulf2 conditional knockout (Sulf2 CKO) mouse line. After bleomycin exposure, Sulf2 CKO mice exhibited enhanced neutrophil infiltration in the lung, with elevated levels of total protein, lactate dehydrogenase, and cytokines (granulocyte colony-stimulating factor and interferon-γ-inducible protein 10) in bronchoalveolar lavage fluid compared with wild-type littermates. We further showed that both the p53-p21 DNA damage response and the transforming growth factor-β1 signaling pathway were up-regulated in Sulf2 CKO mice compared with wild-type. Finally, Sulf2 CKO mice suffered increased mortality after bleomycin exposure. In conclusion, Sulf2 expression in type II AECs plays a protective role in epithelial injury, inflammation and mortality.

Isolation and Identification of Rickettsia raoultii in Human Cases: A Surveillance Study in 3 Medical Centers in China.

Rickettsia raoultii is frequently detected in multiple tick species, whereas human infection remains scarcely studied. A surveillance study was performed at 3 sentinel hospitals in China, to recruit participants with suspected tick exposure. Rickettsia raoultii infection was identified through polymerase chain reaction, followed by sequencing, and confirmed serologically. Isolation by cell culture was performed and the isolates were genome sequenced. Twenty-six subjects were determined to have R. raoultii infection, including 7 with asymptomatic infection, 15 with mild to moderate illness, and 4 with severe illness. Common nonspecific manifestations in the 19 patients with mild to moderate or severe illness included fever (100%), malaise (95%), myalgia (58%), lymphadenopathy (53%), and nausea (42%). Only 5% of them had rash, and 16% had eschar. Scalp eschar and neck lymphadenopathy after a tick bite syndrome was only seen in 2 patients. Of the 4 patients with severe complications, 3 developed pulmonary edema, and 1 developed clouding of consciousness and lethargy. Frequent abnormalities of laboratory testing included leukopenia, thrombocytopenia, lymphopenia, neutropenia, hypoproteinemia, and elevated levels of total bilirubin, hepatic aminotransferases, lactate dehydrogenase, and creatine kinase. All the 19 patients recovered without sequelae after receiving doxycycline treatment. Two R. raoultii strains were isolated, and a significantly less degraded genome was observed than other more virulent Rickettsia strains, indicating a low pathogenicity of the current strain. Human infection with R. raoultii has a wide clinical spectrum that ranged from subclinical infection to severe complications. Physicians need to be aware of the high potential and clinical complexity of R. raoultii infection, to ensure appropriate testing and treatment in endemic regions.

Efeitos de um salgante isento de sódio sobre marcadores sanguíneos bioquímicos hepáticos, renais e cardíacos de ratos normo e hipertensos

Introduo: A hipertenso arterial um dos fatores de risco para doenas cardiovasculares, estando diretamente associada ao elevado consumo de sdio. Objetivo: Avaliar os nveis de marcadores de leso heptica, renal e cardaca em ratos hipertensos comparados aos seus controles normotensos, tratados com um salgante isento de sdio, gua ou NaCl. Mtodos: Ratos hipertensos (SHR) e seus controles normotensos (NWR) foram divididos em 3 grupos (n=7): G1 (gua); G2 (soluo aquosa contendo NaCl 70 mg/kg/dia); G3 (soluo aquosa contendo salgante sem sdio 70 mg/kg/dia). Aps 30 dias, o sangue dos animais foi processado. Resultados: No houve diferena entre os nveis sricos de creatina quinase total, creatina quinase-MB, lactato desidrogenase, cido rico, aspartato aminotransferase e fosfatase alcalina tanto nos NWR como nos SHR tratados com NaCl ou Salgante. Houve diminuio da creatinina nos NWR e SHR tratados com NaCl e Salgante em relao aos controles (p0,005). Concluses: A suplementao diria com o Salgante e NaCl diminuiu os nveis sricos de creatinina nos grupos NWR e SHR. Contudo, no houve modificao nos nveis sricos de marcadores de leso cardaca e heptica.

Immunobiochemical modulations caused by clomazone in Swiss albino mice

BackgroundRecently, we reported immunological and hematological perturbations in Swiss albino mice exposed to clomazone (CMZ) (Nassef, The Egyptian Journal of Experimental Biology (Zoology) 13(1):91–101, 2017).AimTo continue searching immunological perturbations of CMZ, the main goal of the current study was to investigate the probable immunobiochemical perturbations caused by CMZ and to evaluate the alleviating role of vitamin C.MethodsTo asses this goal, mice were intraperitoneally (i.p.) injected with vitamin C (1136 μM/kg), CMZ (46 μM/kg), or CMZ plus vitamin C with the same dose of each, daily for 4 weeks. Changes in relative weights of immune-related organs (spleen and thymus), renal functions (urea and creatinine), liver functions [alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), lactate dehydrogenase (LDH) and total protein], and immunoglobulin (Ig) isotype (IgA, IgG, and IgM) concentrations in addition to the proliferative capacity of CMZ-exposed murine lymphocytes were investigated.ResultsResults showed that CMZ injection caused a significant decrease in body weight gain along with significant decrease in the relative weights of the spleen and thymus. Values of ALT, AST, and ALP were significantly elevated, while total protein and LDH were significantly decreased in CMZ-exposed mice. CMZ injection led to significant increases in the levels of serum urea and creatinine. Moreover, the levels of serum IgA, IgG, and IgM in CMZ-treated mice were significantly lower than those in PBS-treated mice. Reduced lymphocyte proliferation capacity was observed in CMZ-treated mice. Interestingly, pre-treatment of vitamin C to CMZ-exposed mice mildly alleviated CMZ-induced immunobiochemical perturbations. Therefore, vitamin C mildly alleviated CMZ-induced immunobiochemical impacts, but it was not completely protective.ConclusionFurther studies are needed to assess the relationships between antioxidants and CMZ-induced immunobiochemical perturbations.

Gynura segetum-related hepatic sinusoidal obstruction syndrome: a national multicenter clinical study

Objective To investigate the clinical features, diagnosis and treatment of Gynura segetum-related hepatic sinusoidal obstruction syndrome (HSOS). Methods From January 2010 to May 2017, 458 hospitalized patients with HSOS from 29 hospitals were enrolled, and among them 239 cases were Gynura segetum-related HSOS. The diagnostic value of clinical signs in Gynura segetum-related HSOS were evaluated by Seattle criteria which used in HSOS caused by hemopoietic stem cells transplantation. The pathological diagnosis of liver biopsy was taken as gold standard. The diagnostic value of computed tomography (CT)/magnetic resonance imaging (MRI) in Gynura segetum-related HSOS was also investigated. Sensitivity, specificity, positive predictive value, negative predictive value, accuracy and Kappa value were used for the assessment of diagnostic value. Cox regression analysis was performed for prognosis analysis. Results Among 362 patients with drugs-related HSOS, 239 cases (66.02%) was Gynura segetum-related HSOS and 232(97.07%) of the 239 patients with Gynura segetum-related HSOS presented with ascites. The diagnostic sensitivity and specificity of ascites in HSOS were 97.07% and 75.86%, respectively, and the Kappa value was 0.751. The diagnostic sensitivities of patchy map-like enhancement and (or) heterogeneous hypoattenuation of CT or inhomogeneous signal of MRI were 100.0% and 97.4%, respectively; and the specificities were 88.9% and 100.0%, respectively, and both of the Kappa value were more than 0.75, with excellent consistency. The accuracies of patchy enhancement, heterogeneous hypoattenuation of CT or inhomogeneous signal of MRI and ascites were all over 90%. Among 239 patients with Gynura segetum-related HSOS, 229 (95.82%) patients were treated with hepatoprotectants and diuretics, and 105 (43.93%) patients received anticoagulant drugs. The mortality rate was 8.37% (20/239). The percentage of patients with no improvement or deterioration was 17.57% (42/239). Increased total bilirubin and lactic dehydrogenase levels were related with poor prognosis (the relative risk was 1.012 and 1.009, respectively; both P<0.05). Conclusions Gynura segetum is a major cause of hospitalized patients with HSOS in China. Ascites is the major clinical manifestation. The patchy enhancement, heterogeneous hypoattenuation of CT or inhomogeneous signal of MRI are the main CT/MRI signs of HSOS. There are no reliable and effective treatments for Gynura segetum-related HSOS and the mortality is relatively low. Key words: Hepatic sinusoidal obstruction syndrome; Pyrrolizidine alkaloids; Multicenter study; Retrospective studies