Background. Previous research has detailed the hemisphere dependence and specific kinematic deficits observed for the less-affected arm of patients with unilateral stroke. Objective. We now examine whether functional motor deficits in the less-affected arm, measured by standardized clinical measures of motor function, also depend on the hemisphere that was damaged and on the severity of contralesional impairment. Methods. We recruited 48 left-hemisphere-damaged (LHD) participants, 62 right-hemisphere-damaged participants, and 54 age-matched control participants. Measures of motor function included the following: (1) Jebsen-Taylor Hand Function Test (JHFT), (2) Grooved Pegboard Test (GPT), and (3) grip strength. We measured the extent of contralesional arm impairment with the upper-extremity component of the Fugl-Meyer (UEFM) assessment of motor impairment. Results. Ipsilesional limb functional performance deficits (JHFT) varied with both the damaged hemisphere and severity of contralesional arm impairment, with the most severe deficits expressed in LHD participants with severe contralesional impairment (UEFM). GPT and grip strength varied with severity of contralesional impairment but not with hemisphere. Conclusions. Stroke survivors with the most severe paretic arm impairment, who must rely on their ipsilesional arm for performing daily activities, have the greatest motor deficit in the less-affected arm. We recommend remediation of this arm to improve functional independence in this group of stroke patients.

Non-alcoholic fatty liver disease (NAFLD) and -steatohepatitis (NASH) imply a state of excessive fat built-up in livers with/or without inflammation and have led to serious medical concerns in recent years. Antrodan (Ant), a purified β-glucan from A. cinnamomea has been shown to exhibit tremendous bioactivity, including hepatoprotective, antihyperlipidemic, antiliver cancer, and anti-inflammatory effects. Considering the already well-known alleviating bioactivity of A. cinnamomea for the alcoholic steatohepatitis (ASH), we propose that Ant can be beneficial to NAFLD, and that the AMPK/Sirt1/PPARγ/SREBP-1c pathways may be involved in such alleviations. To uncover this, we carried out this study with 60 male C57BL/6 mice fed high-fat high-fructose diet (HFD) for 60 days, in order to induce NAFLD/NASH. Mice were then grouped and treated (by oral administration) as: G1: control; G2: HFD (HFD control); G3: Ant, 40 mgkg (Ant control); G4: HFD+Orlistat (10 mg/kg) (as Orlistat control); G5: HFD+Ant L (20 mg/kg); and G6: HFD+Ant H (40 mg/kg) for 45 days. The results indicated Ant at 40 mg/kg effectively suppressed the plasma levels of malondialdehyde, total cholesterol, triglycerides, GOT, GPT, uric acid, glucose, and insulin; upregulated leptin, adiponectin, pAMPK, Sirt1, and down-regulated PPARγ and SREBP-1c. Conclusively, Ant effectively alleviates NAFLD via AMPK/Sirt1/CREBP-1c/PPARγ pathway.

Human genome is continuously exposed to various DNA damaging agents including reactive oxygen species. Of various forms of DNA damage, double-strand breaks (DSBs) in DNA are the most detrimental because of the mutagenicity and cytotoxicity. To combat the serious threats posed by DSBs, cells evolved various homologous and non-homologous recombination repair mechanisms. However, some repair mechanisms appear to be involved in the induction of genome rearrangements such as deletions. To analyze the deletion mutations in a whole body system, gpt delta mice were established. In this mouse model, deletions in lambda, DNA integrated in the chromosome are preferentially selected as Spi(-) phages, which can then be subjected for molecular analysis. Here, we reported the sequence characteristics of deletions induced by ionizing radiations in the liver, ultraviolet light beta in the epidermis, mitomycin C in the bone marrow and heterocyclic amine PhIP in the colon. To our knowledge, this is the first report in which in vivo deletion mutations are systematically analyzed at the molecular level. About half of the large deletions occur between short direct-repeat sequences and the remainder had flush ends, suggesting that they are generated during the repair of DSBs in DNA. The results also suggest that mutation induction and repair mechanisms may vary depending on the type of organs/tissues examined, i.e., germ cells versus somatic cells or highly proliferating cells versus slowly proliferating cells. Possible mechanisms of intrachromosomal deletion mutations are discussed.

The objective of this study was to analyse the structure of CPP-2, and to observe the pharmacological effects of CPP-2 on lipid metabolism and oxidative stress. CPP-2, eluted as two main fractions comprised of two polysaccharides with Mw of 307 and 3.7kDa, was mainly consisted of rhamnose, mannose, glucose and galactose in a molar ratio of 1.00:0.78:3.22:0.45. The results showed that treatment with CPP-2 could improve blood lipid levels (TC, TG, HDL-C and LDL-C), liver lipid levels (TC and TG) and antioxidant status (SOD, T-AOC, GSH-PX, MDA and LPO). In addition, the histopathological observations of mice livers and the GPT activities indicated that CPP-2 could attenuate liver cell injury. The present findings demonstrated that CPP-2 might be effective in lowering lipid and protecting against HFE-induced hyperlipidemia and non-alcoholic fatty liver.

Epidermolysis bullosa (EB) is a heterogeneous group of genetic bullous skin diseases. The EB simplex group (EBS) is characterized by intraepidermal blistering. EBS-Ogna was first described as a separate entity based on clinical studies. Later genetic linkage of EBS-Ogna to the GPT locus for glutamate pyruvate transaminase (alanine transaminase) was detected and GPT was assigned to chromosome 8, then to the terminal long arm band 8q24. Plectin is an abundant and widespread cytoskeletal protein which has been proposed as a general crosslinking element of intermediate filaments. Human plectin has recently been cloned and in situ hybridized to chromosome 8q24. To examine whether plectin could be associated with EBS-Ogna we performed an immunohistochemical study with a panel of mAbs to rat plectin. Interestingly, 2 of these mAbs showed strong intracellular staining of the suprabasal and basal layer of the epidermis in all control samples, whereas no reactivity of the basal layer was found in the Ogna group. These results strongly suggest that plectin is involved in the pathogenesis of EBS-Ogna.

Both heat-killed Lactobacillus plantarum (HK-LP) and β-glucan (BG) play important roles in growth performance, feed utilization and health status of fish. Therefore, a feeding trial was conducted to determine the interactive effects of dietary HK-LP and BG on growth performance, digestibility, oxidative status and immune response of red sea bream for 56 days. A significant interaction was found between HK-LP and BG on final body weight, total plasma protein, glucose, serum bactericidal activity (BA), total serum protein, serum alternative complement pathway (ACP) activity, protein and dry matter digestibility coefficients (P < 0.05). In addition, body weight gain, specific growth rate, feed intake, protein efficiency ratio as well as serum lysozyme activity, ACP activity and mucus secretion were significantly affected by either HK-LP or BG (P < 0.05). Further, feeding 0.025% HK-LP combined with 0.1% BG significantly increased serum peroxidase activity compared with the other groups (P < 0.05). However, protein body content, somatic parameters, total bilirubin, blood urea nitrogen, glutamyl oxaloacetic transaminase (GOT), glutamic-pyruvate transaminase (GPT), triglycerides and mucus BA were not significantly altered by supplementations (P>> 0.05). Interestingly, fish fed with both HK-LP at (0.025 and 0.1%) in combination with BG at (0 and 0.1%) showed higher oxidative stress resistance. Under the experimental conditions, dietary HK-LP and BG had a significant interaction on enhancing the growth, digestibility and immune responses of red sea bream.

OBJECTIVE

Training in and assessment of consultation skills are high on the agenda of vocational training institutes for postgraduate training. There is a need to establish valid and reliable instruments to assess consultation skills in authentic settings. We investigated the number of assessors and observations needed to achieve reliable assessments of the consultation skills of general practice trainees (GPTs) using a communication instrument (MAAS-Global) and either standardised patient (SP) encounters or videotaped real patient (RP) encounters.

METHODS

Eight teachers at the Vrije Universiteit (VU) University Medical Centre in Amsterdam attended a training course on the use of the MAAS-Global instrument, which they subsequently used to assess the consultation skills of 53 GPTs in 176 videotaped consultations (102 with SPs, 74 with RPs). All consultations were randomly allocated and assessed by two teachers independently. The reliability of the ratings was estimated using generalisability theory.

RESULTS

It was easier to obtain acceptable reliability using RP consultations than SP consultations. Two assessors and five consultations were required to achieve minimal reliability (generalisability coefficient 0.7) with RPs, whereas three assessors and 30 consultations were needed to achieve minimal reliability with SPs.

CONCLUSIONS

Inter-observer and context variability in the assessment of the consultation skills of GPTs remains high. To achieve acceptable levels of reliability, large samples of observations are required in both formats, but, interestingly, RP encounters require a smaller sample than SP encounters.

Spontaneous mutagenesis is thought to play a crucial role in spontaneous carcinogenesis. We recently described a new mathematical model for estimation of the spontaneous mutation rate (mutation/gene/generations) based on the assumption that mutations are fixed in the S-phase of the cell cycle. With this definition, the spontaneous mutation rate should be independent of the growth rate. In the present study, we tested this hypothesis, using cell line G12, a transgenic Chinese hamster V79 derivative, which contains a single copy of the Escherichia coli gpt gene as a target for mutagenesis. The growth rate was modulated by varying the serum concentration or the seeding density, or by addition of suramin, transforming growth factor beta, or dichlorobenzimidazole riboside to the medium. Significant increases in the spontaneous mutation rate occurred when cell proliferation was blocked by serum deprivation. Density-dependent inhibition of growth and inhibition of growth by suramin, transforming growth factor beta, or dichlorobenzimidazole riboside did not result in significant increases in spontaneous mutation rates. The level of oxidants in cells cultivated in the presence of low concentrations of serum was higher compared to control cells, suggesting that the increases in the spontaneous mutation rates under low serum conditions may be partly a result of oxidative stress due to a lack of serum antioxidants. This was shown to be the case, because spontaneous mutation rates were significantly reduced in serum-depleted cells when antioxidants were added to the medium. We suggest that during carcinogenesis, when tumors are in a prevascularized state, the spontaneous mutation rate may be elevated, and this process may contribute to the genetic instability of the tumor cells.

The protective effect of fresh aloe vera (AV) leaves extract on lindane (LD) - induced hepatoxicity and genotoxicity was studied. Serum levels of hepatic enzyme markers: glutamate pyruvate transaminase (GPT), glutamate oxaloacetate transaminase (GOT), gamma glutamyl transferase (GGT) and alkaline phosphatase (ALP) were determined after oral administration of aloe vera leaves extract and lindane. The level of polychromatic erythrocytes was also observed. Pretreatment with aloe vera leaves extract at concentration of 1.0 ml/kg body weight significantly decreased (P<0.05) the serum levels of GPT (by 41.8%), GOT (by 36.5%), GGT (by 14.3%) and ALP (by 10.7%) induced by 100mg/kg body weight of lindane. The level of polychromatic erythrocytes observed was not statistically significant when compared to control.

OBJECTIVE

Our objective was to evaluate whether COX-2 inhibition with FK3311, a selective cyclooxygenase (COX)-2 inhibitor, improves transplanted liver function.

METHODS

Inbred male Lewis rats weighing 200-260 g were used. The donor liver was perfused with cold University of Wisconsin (UW) solution and then stored in the same solution at 4 degrees C for 18 hr. After the preservation period, orthotopic liver transplantation was performed. Animals were divided into three groups: the control group; the FK low-dose group (1 mg/kg FK3311 i.v. 20 min before reperfusion); and the FK high-dose group (3 mg/kg FK3311 i.v. 20 min before reperfusion). Survival rate, serum GOT and GPT levels, liver tissue blood flow, and serum thromboxane B(2) (TxB(2)) levels were compared among groups.

RESULTS

Survival rate was significantly better (p <. 05) and serum GOT levels 30 min after reperfusion were significantly lower (p <. 05) in the FK high-dose group compared to the other two groups. Four hours after reperfusion, GPT levels and liver tissue flow were significantly (p <. 05) better in the FK high-dose group compared to the control. Both 30 min and 4 hr after reperfusion, serum TxB(2) levels were significantly lower in the FK high-dose group compared to the control (p <. 05).

CONCLUSIONS

COX-2 activity results in deteriorated liver function after I/R injury associated with transplantation, and selective COX-2 inhibition improved liver graft function.

Carbon tetrachloride (CCl(4)) causes chronic hepatitis, featuring an increase in hepatic hydroxyproline, spleen weight and serum GPT levels and a decrease in plasma albumin levels. Crude extracts of fresh whole plants of Anoectochilus formosanus showed inhibition of chronic hepatitis induced by CCl(4) in mice. Bioactivity-guided fractionation and spectroscopic analysis revealed that kinsenoside was the most active compound. In an in vitro study, the LD(50) values for H(2)O(2)-induced cytotoxicity in BALB/c normal liver cells were significantly higher after kinsenoside pretreatment than after vehicle alone, further confirming that kinsenoside shows significant antihepatotoxic activity.

Human papilloma virus (HPV)-associated oropharyngeal cancer (OPC) is an independent tumour type with regard to cellular, biological, and clinical features. The use of non-invasive biomarkers such as circulating tumour DNA (ctDNA) may be relevant in early diagnosis and eventually improve the outcomes of patients with head and neck squamous cell carcinoma (HNSCC). Genome-wide discovery using RNA sequencing and reduced representation bisulfite sequencing yielded 21 candidates for methylation-targeted genes. A verification study (252 HNSCC patients) using quantitative methylation-specific PCR (Q-MSP) identified 10 genes (ATP2A1, CALML5, DNAJC5G, GNMT, GPT, LY6D, LYNX1, MAL, MGC16275, and MRGPRF) that showed a significant increase recurrence in methylation groups with OPC. Further study on ctDNA using Q-MSP in HPV-associated OPC showed that three genes (CALML5, DNAJC5G, and LY6D) had a high predictive ability as emerging biomarkers for a validation set, each capable of discriminating between the plasma of the patients from healthy individuals. Among the 42 ctDNA samples, methylated CALML5, DNAJC5G, and LY6D were observed in 31 (73.8%), 19 (45.2%), and 19 (45.2%) samples, respectively. Among pre-treatment ctDNA samples, methylated CALML5, DNAJC5G, and LY6D were observed in 8/8 (100%), 7/8 (87.5%), and 7/8 (87.5%) samples, respectively. Methylated CALML5, DNAJC5G, and LY6D were found in 2/8 (25.0%), 0/8 (0%), and 1/8 (12.5%) of the final samples in the series, respectively. Here, we present the relationship between the methylation status of three specific genes and cancer recurrence for risk classification of HPV-associated OPC cases. In conclusion, ctDNA analysis has the potential to aid in determining patient prognosis and real-time surveillance for disease recurrences and serves as an alternative method of screening for HPV-associated OPC.

Rhabdomyolysis is a condition affecting body homeostasis that results from impaired supply of muscles with energy, nutritional factors and blood. Complex pathophysiological mechanism causes that extended myolysis may complicate different clinical conditions, such as: crush syndrome, excessive physical effort (work, seizures), toxic effect of drugs and toxins, water-electrolyte disturbances, congenital enzymatic deficiencies etc. It seems that on the cellular level, essential role is played by excessively high intracytoplasmatic calcium level, which affects metabolic processes. So high calcium level is a consequence of muscular cell injury irrespective to its reason. It manifests clinically as muscular weakness, pal and oedema and laboratory tests reveal elevated CK, GOT, GPT, aldolase and LDH levels as well as dark brown urine colour. Demonstration of elevated serum myoglobin level or its presence in urine directly confirms development of rhabdomyolysis. In unfavorable conditions, rhabdomyolysis may result in acute renal failure. Appropriately early and adequate water supply and alkalization plays an essential role in prevention of impairment in renal function. In advanced phase of renal failure, hemodialysis is a standard treatment.

BACKGROUND

Treatment of Chagas disease, caused by Trypanosoma cruzi, relies on nifurtimox and benznidazole (BZL), which present side effects in adult patients, and natural resistance in some parasite strains. Hydroxymethylnitrofurazone (NFOH) is a new drug candidate with demonstrated trypanocidal activity; however, its safety is not known.

METHODS

HepG2 cells dose response to NFOH and BZL (5-100 µM) was assessed by measurement of ROS, DNA damage and survival. Swiss mice were treated with NFOH or BZL for short-term (ST, 21 d) or long-term (LT, 60 d) periods. Sera levels of cellular injury markers, liver inflammatory and oxidative stress, and fibrotic remodeling were monitored.

RESULTS

HepG2 cells exhibited mild stress, evidenced by increased ROS and DNA damage, in response to NFOH, while BZL at 100 µM concentration induced >33% cell death in 24 h. In mice, NFOH ST treatment resulted in mild-to-no increase in the liver injury biomarkers (GOT, GPT), and liver levels of inflammatory (myeloperoxidase, TNF-α), oxidative (lipid peroxides) and nitrosative (3-nitrotyrosine) stress. These stress responses in NFOH LT treated mice were normalized to control levels. BZL-treated mice exhibited a >5-fold increase in GOT, GPT and TNF-α (LT) and a 20-40% increase in liver levels of MPO activity (ST and LT) in comparison with NFOH-treated mice. The liver inflammatory infiltrate was noted in the order of BZL>vehicle≥NFOH and BZL>NFOH≥vehicle, respectively, after ST and LT treatments. Liver fibrotic remodeling, identified after ST treatment, was in the order of BZL>vehicle>NFOH; lipid deposits, indicative of mitochondrial dysfunction and in the order of NFOH>vehicle>BZL were evidenced after LT treatment.

CONCLUSIONS

NFOH induces mild ST hepatotoxicity that is normalized during LT treatment in mice. Our results suggest that additional studies to determine the efficacy and toxicity of NFOH are warranted.

BACKGROUND

Oxidative stress has been suspected to influence graft survival and prognosis in pediatric recipients of living related liver transplantation (LRLT).

OBJECTIVE

We determined the oxidative status of pediatric LRLT recipients during their regular outpatient follow-up visits, and looked for a relationship between oxidative status and post-liver transplantation (post-LTx) duration.

METHODS

The study included 43 patients (20 males and 23 females) between the ages of 1.6 and 25.1 years (median 10.7 years) who had undergone LRLT from 5 months to 17.5 years (median 7 years) prior to the study, between the ages of 1.2 and 14.4 years (median 3.5 years).

METHODS

Serum glutamic pyruvic transaminase (GPT), glutamic oxaloacetic transaminase (GOT), gamma-glutamyl transpeptidase (γ-GTP), alkaline phosphatase (ALP), lactate dehydrogenase (LDH), direct bilirubin and choline-esterase were measured as part of the patients' regular follow-up visits. Serum total hydroperoxide (TH) and biological antioxidative potential (BAP) were measured using the free radical analytic system which requires 20 μl of serum and 10 min of processing time for each sample. Oxidative stress index (OSI) was calculated as the ratio of TH to BAP.

RESULTS

Serum OSI correlated positively with serum levels of GOT, GPT, LDH, ALP, γ-GTP and direct bilirubin. Serum OSI, TH, LDH, ALP and GOT correlated negatively with post-LTx duration. Serum BAP correlated positively with post-LTx duration. Serum TH correlated positively with serum GOT and γ-GTP, but negatively with serum BAP.

CONCLUSIONS

(1) The OSI, which can be calculated based on data acquired through a simple outpatient procedure, can serve as an index of our patients' laboratory results and oxidative status. (2) The LRLT recipients in our study were at risk for oxidative stress early in the post-operative period, but this risk subsided with time.

The present study evaluates the effects of chitooligosaccharides (COS) for the management of alloxan induced diabetes in mice. For the management of the carbohydrate metabolism in diabetes by the COS, the amount of glucose in blood along with quantification of glycogen in liver were measured and noted a significant recovery in respect to diabetic control group. As hyperlipidemia and oxidative stress are the disorders of diabetes so, we have also assessed the serum levels of total cholesterol (TC), triglyceride (TG), low density lipoprotein cholesterol (LDLc), very low density lipoprotein cholesterol (VLDLc) and high density lipoprotein cholesterol (HDLc). For the recovery of oxidative stress the SOD MDA catalase in liver and GOT and GPT activities in serum were measured. The COS results a significant recovery in the levels of above mentioned biosensors of lipid profile when treated to experimentally induce diabetic mice. The effect of COS at the dose of 10mg/kg body weight was found to be a potent agent for diabetes and complication associated with this disease. The COS has no toxic effect in general which has been focused here by the monitoring of COS dose in normal healthy mice. The results of this study enlighted that the COS has antidiabetic, antihyperlipidemic and antioxidative activities.

OBJECTIVE

To assess the health status, attitude and level of awareness of safe pesticide handling practices of farm workers engaged in the application of pesticides on agricultural farms.

METHODS

Cross sectional study.

METHODS

Two farms in northwest Ethiopia, 2004.

METHODS

Farm workers of job categories; sprayers, pest assessors, supervisors, spraymachine mechanics and tractor operators.

RESULTS

The farm workers had respiratory symptoms of cough, phlegm and wheezing. Systolic and diastolic blood pressures did not show abnormalities. Liver function tests showed elevated values. Respiratory symptoms in the farm workers revealed that cough phlegm and wheezing at Ayehu farm were significantly (p < 0.05) higher than the controls. Alkaline phosphatase (ALP) at Birr Farm in the sprayers and mechanics were significantly higher than the controls (p < 0.05). The ALP value in the sprayers, glutamate pyruvate transaminase (GPT) in the assessors and glutamate oxaloacetate transaminase (GOT) in the sprayers and mechanics at Ayehu were significantly higher than the controls (p < 0.05). From a total of 82 farm workers 35.7% at Birr and 75% at Ayehu Farm described that they were not formally instructed about safe pesticide handling methods.

CONCLUSIONS

The farm workers health is affected by the unwise use of pesticides. The level of awareness and attitude on safe pesticide handling practices is low. It is recommended that appropriate type of personal protective device (PPD), in service training about the proper use of chemical pesticides and periodic medical check-up should be fulfilled to minimise the adverse health effects of chemical pesticides.

In this study, the hepatoprotective effect of dieckol on carbon tetrachloride (CCl4) induced hepatic damages in ICR mice liver was investigated. Mice were randomly divided into 4 groups such as saline treated (negative control), CCl4 treated (positive control), CCl4+dieckol (5mg/kg mouse) and CCl4+dieckol (25mg/kg mouse), respectively. The body weights and survival rates of mice, followed by dieckol treatments were significantly increased compared to the positive control. The level of GOT, GPT and MDA in the serum of the dieckol treated groups were reduced dose dependently than the control, significantly. The antioxidant enzymes including CAT, and GSH-px levels were increased significantly compared to the positive control. However, no significant differences were observed on hepatic histophathological analysis in dieckol treated groups dose dependently. Down-regulation of Bax and up-regulation of Bcl-xl protein expressions were observed in liver tissues of the dieckol administered groups. These results suggested that, dieckol can be developed as a therapeutic agent for liver disease by oxidative stress.

Most of the previously obtained data on cosmonauts' metabolic state concerned certain stages of the postflight period. In this connection, all conclusions, as to metabolism peculiarities during the space flight, were to a large extent probabilistic. The purpose of this work was study of metabolism characteristics in cosmonauts directly during long-term space flights. In the capillary blood samples taken from a finger, by "Reflotron IV" biochemical analyzer, "Boehringer Mannheim" GmbH, Germany, adapted to weightlessness environments, the activity of GOT, GPT, CK, gamma-GT, total and pancreatic amylase, as well as concentration of hemoglobin, glucose, total bilirubin, uric acid, urea, creatinine, total, HDL- and LDL cholesterol, triglycerides had been determined. HDL/LDL-cholesterol ratio also was computed. The crewmembers of 6 main missions to the "Mir" orbital station, a total of 17 cosmonauts, were examined. Biochemical tests were carried out 30-60 days before launch, and in the flights different stages between the 25-th and the 423-rd days of flights. In cosmonauts during space flight had been found tendency to increase, in compare with basal level, GOT, GPT, total amylase activity, glucose and total cholesterol concentration, and tendency to decrease of CK activity, hemoglobin, HDL-cholesterol concentration, and HDL/LDL - cholesterol ratio. Some definite trends in variations of other determined biochemical parameters had not been found. The same trends of mentioned biochemical parameters alterations observed in majority of tested cosmonauts, allows to suppose existence of connection between noted metabolic alterations with influence of space flight conditions upon cosmonaut's body. Variations of other studied blood biochemical parameters depends on, probably, pure individual causes.

Leukotriene B4 (LTB4) is a potent leukocyte chemoattractant, acting on specific receptors, BLT receptors. The aim of this study was to examine the mechanism of action of LTB4 in the guinea-pig lung, using strips of lung parenchyma (GPLP), spirals of trachea (GPT) and bronchus (GPB) and rings of pulmonary artery (GPPA). Mechanical responses were studied in organ baths, and mediator release was assessed using enzyme immuno assay. LTB4 induced similar contractions of GPLP and GPPA, whereas LTB4 had only small contractile effects in GPT and GPB. In addition, the contractile response to LTB4 was reproduced in the human pulmonary artery. In the GPLP, the unselective BLT receptor antagonist ONO-4057 abolished the contractions induced by LTB4, whereas the selective BLT1 receptor antagonist U-75302 only partly inhibited the LTB4-induced contractions. In the GPPA, both antagonists abolished the response to LTB4. The effect of LTB4 in GPPA and GPLP was indirect and mediated by the release of thromboxane A2 and histamine, as supported by selective pharmacologic interventions and measurements of thromboxane B2 and histamine in the organ baths. In conclusion, the results indicate a new biological function of LTB4, namely to constrict isolated pulmonary arteries. Moreover, the findings suggest that the LTB4-induced contractions of GPPA were mediated by a BLT1 receptor, whereas BLT2 receptor activation accounted for a major part of the contraction of GPLP, making the latter preparation a suitable assay for BLT2 receptors. British Journal of Pharmacology (2004) 141, 449-456. doi:10.1038/sj.bjp.0705641

We have computationally investigated the structure and stability of all 16 combinations of two out of the four natural DNA bases A, T, G and C in a di-2'-deoxyribonucleoside-monophosphate model DNA strand as well as in 10 double-strand model complexes thereof, using dispersion-corrected density functional theory (DFT-D). Optimized geometries with B-DNA conformation were obtained through the inclusion of implicit water solvent and, in the DNA models, of sodium counterions, to neutralize the negative charge of the phosphate groups. The results obtained allowed us to compare the relative stability of isomeric single and double strands. Moreover, the energy of the Watson-Crick pairing of complementary single strands to form double-helical structures was calculated. The latter furnished the following increasing stability trend of the double-helix formation energy: d(TpA)2 <d(CpA)2 <d(ApT)2 <d(ApA)2 <d(<em>GpT</em>)2 <d(GpA)2 <d(ApG)2 <d(CpG)2 <d(GpG)2 <d(GpC)2, where the energy differences between the last four dimers, d(ApG)2, d(CpG)2, d(GpG)2 and d(GpC)2, is within 4.0 kcal mol(-1), and the energy between the most and the least stable isomers is 13.4 kcal mol(-1). This trend shows that the formation energy essentially increases with the number of hydrogen bonds per base pair, that is two between A and T and three between G and C. Superimposed on this main trend are more subtle effects that depend on the order in which bases occur within a strand from the 5'- to the 3'-end.

Wumeng semi-fine wool sheep are affected by a disease, characterized by emaciation, stiffness and trembling of the limbs, weakness and inability to stand, and sudden death. The objective of the study was to determine possible relationships between the disease and mineral deficiencies. Samples of wool, blood, and liver were collected from affected and healthy sheep. Samples of soil and forage were collected from affected and unaffected areas. The samples were used for hematological and biochemical analyses and mineral nutrient measurements. Results showed that selenium concentrations in forage and soil samples from affected areas were significantly lower than those from unaffected areas (P < 0.01). Meanwhile, selenium concentrations of wool, blood, and liver from the affected sheep were also significantly lower than those from the healthy sheep (P < 0.01). The mean concentration of hemoglobin (Hb), packed cell volume (PCV), and mean corpuscular hemoglobin (MCH) from the affected sheep were significantly lower than those from the healthy sheep (P < 0.01). Serum glutathione peroxidase (GSH-Px), superoxide dismutase (SOD), and catalase (CAT) activity in the affected sheep were significantly lower than those in the healthy sheep (P < 0.01). Serum creatine phosphokinase (CPK), lactate dehydrogenase (LDH), glutamate pyruvate transaminase (GPT), glutamic oxaloacetic transaminase (GOT), alkaline phosphatase (ALP), and malondialdehyde (MDA) values in the affected sheep were significantly higher than those in the healthy sheep (P < 0.01). Serum concentrations of free triiodothyronine (FT₃) and triiodothyronine (TT₃) in the affected sheep were significantly lower than those in the healthy sheep; serum concentrations of free tetraiodothyronine (FT₄) and tetraiodothyronine (TT₄) in the affected sheep were significantly higher than those in the healthy sheep (P < 0.01). But the administration of selenium and vitamin E by hypodermic injection prevented and cured the disease. The injection contains 0.1% and 5% of sodium selenite and vitamin E, respectively. A single dose is 6, 6, and 2 mL for mature ewe, mature ram, and lamb, respectively, repeated only once 15 days later. This study demonstrated that the disorder of Wumeng semi-fine wool sheep was mainly caused by the selenium deficiency in soil and forage.

A 74-year-old male was admitted to hospital with acute rhabdomyolysis and myoglobinuria due to hypokalemia. The hypokalemia resulted from diuretic treatment. He had no family history of myopathy, and no diarrhea and vomiting. The neurological examination revealed painful quadriplegia. The blood pressure was 160/74 mm Hg. Laboratory examination showed hypokalemic and hypochloremic metabolic alkalosis (serum K 1.5 mEq/l, serum Cl 89 mEq/l, base excess + 20.9, HCO3- 44.9 mmol/l, pH 7.563) and marked elevations of serum CPK, LDH, GOT, GPT and myoglobin. Endocrinological and renal functions were normal. Muscle biopsy revealed marked necrosis with remarkable phagocytosis and vacuolar degeneration. The cessation of diuretics and intravenous infusion of potassium chloride resulted in a marked improvement in clinical and laboratory findings. The diuretics-induced hypokalemic myopathy is rare in the literature.