Change in malate dehydrogenase and alpha amylase activities in Rubus fruticosus and Valeriana jatamansi treated granary weevil, Sitophilus granarius / Mudança nas atividades de malato desidrogenase e alfa amilase em Rubus fruticosus e gorgulho tratado com Valeriana jatamansi, Sitophilus granarius

Poor storage conditions provide favorable environment to stored grain pests for their growth. The bio-pesticides are the best alternatives to synthetic pesticides. Present study was conducted to compare toxicity of Rubus fruticosus and Valeriana jatamansi against granary weevil, Sitophilus granarius and subsequent changes in enzyme activity responsible for grain damage. In current research 5 g of R. fruticosus fruit and V. jatamansi rhizome powders were tested separately against S. granarius, in 50 g wheat whole grains for seven days in comparison with the control. The enzymatic activity of malate dehydrogenase and α-amylase was observed in the cellular extracts of S. granarius. The insects were crushed and homogenized in phosphate-buffer solution and centrifuged at 10000 rpm for 5 minutes. For the enzymatic measurement supernatant was tested; the spectrophotometer was adjusted at 340 nm. The reagents were mixed and incubated at 25 °C for five minutes. The cuvettes were placed in the experimental and reference sites of spectrophotometer and recorded the change in absorbance for 3-4 minutes. There was 5.60% and 14.92% reduction in the activity of malate dehydrogenase in R. fruticosus and V. jatamansi, treated insects, respectively. The alpha amylase enzyme activity was 6.82% reduced and 63.63% increase in R. fruticosus and V. jatamansi, treated insects, respectively. Present study addresses that both plant powders are effective against granary weevil by altering enzyme activities so both the plant powders can be used as bio-pesticides against the stored grains pests.

As más condições de armazenamento proporcionam um ambiente favorável às pragas armazenadas para o crescimento. Os biopesticidas são as melhores alternativas aos pesticidas sintéticos. O presente estudo foi conduzido para comparar a toxicidade de Rubus fruticosus e Valeriana jatamansi contra gorgulhos, Sitophilus granarius e subsequentes alterações na atividade enzimática responsáveis ​​por danos aos grãos. Na pesquisa atual, 5 g de frutos de R. fruticosus e pós de rizoma de V. jatamansi foram testados separadamente contra S. granarius, em 50 g de grãos integrais de trigo por sete dias, em comparação com o controle. A atividade enzimática da malato desidrogenase e α-amilase foi observada nos extratos celulares de S. granarius. Os insetos foram esmagados e homogeneizados em solução tampão fosfato e centrifugados a 10000 rpm por 5 minutos. Para a medição enzimática, o sobrenadante foi testado; o espectrofotômetro foi ajustado a 340 nm. Os reagentes foram misturados e incubados a 25 °C por cinco minutos. As cubetas foram colocadas nos locais experimentais e de referência do espectrofotômetro e registradas as alterações na absorbância por 3-4 minutos. Houve redução de 5,60% e 14,92% na atividade da malato desidrogenase em R. fruticosus e V. jatamansi, insetos tratados, respectivamente. A atividade da enzima alfa amilase foi reduzida em 6,82% e aumento de 63,63% em R. fruticosus e V. jatamansi, insetos tratados, respectivamente. O presente estudo aborda que ambos os pós de plantas são eficazes contra o gorgulho do celeiro, alterando as atividades enzimáticas, de modo que ambos os pós de plantas possam ser usados ​​como biopesticidas contra pragas de grãos armazenados.

Functional mechanism of malate dehydrogenase 2 in tumors / 国际肿瘤学杂志

The role of malate dehydrogenase 2 (MDH2) in tumors is double-sided,it has a cancerpromoting effect in some tumors and an inhibitory effect in other tumors.The function of MDH2 is related to energy metabolism,tumor resistance and its pseudo hypoxia.MDH2 plays an important role in the occurrence,development,invasion and metastasis of tumors.An in-depth understanding of the functional mechanism of MDH2 in tumors can provide new molecular targets for tumor intervention in the clinic.

Cancer Energy Metabolism: Shutting Power off Cancer Factory

In 1923, Dr. Warburg had observed that tumors acidified the Ringer solution when 13 mM glucose was added, which was identified as being due to lactate. When glucose is the only source of nutrient, it can serve for both biosynthesis and energy production. However, a series of studies revealed that the cancer cell consumes glucose for biosynthesis through fermentation, not for energy supply, under physiological conditions. Recently, a new observation was made that there is a metabolic symbiosis in which glycolytic and oxidative tumor cells mutually regulate their energy metabolism. Hypoxic cancer cells use glucose for glycolytic metabolism and release lactate which is used by oxygenated cancer cells. This study challenged the Warburg effect, because Warburg claimed that fermentation by irreversible damaging of mitochondria is a fundamental cause of cancer. However, recent studies revealed that mitochondria in cancer cell show active function of oxidative phosphorylation although TCA cycle is stalled. It was also shown that blocking cytosolic NADH production by aldehyde dehydrogenase inhibition, combined with oxidative phosphorylation inhibition, resulted in up to 80% decrease of ATP production, which resulted in a significant regression of tumor growth in the NSCLC model. This suggests a new theory that NADH production in the cytosol plays a key role of ATP production through the mitochondrial electron transport chain in cancer cells, while NADH production is mostly occupied inside mitochondria in normal cells.

Action of Mitochondrial Substrates on Neuronal Excitability in Rat Substantia Gelatinosa Neurons

Recent studies indicate that mitochondria are an important source of reactive oxygen species (ROS) in the spinal dorsal horn. In our previous study, application of malate, a mitochondrial electron transport complex I substrate, induced a membrane depolarization, which was inhibited by pretreatment with ROS scavengers. In the present study, we used patch clamp recording in the substantia geletinosa (SG) neurons of spinal slices, to investigate the cellular mechanism of mitochondrial ROS on neuronal excitability. DNQX (an AMPA receptor antagonist) and AP5 (an NMDA receptor antagonist) decreased the malate-induced depolarization. In an external calcium free solution and addition of tetrodotoxin (TTX) for blockade of synaptic transmission, the malateinduced depolarization remained unchanged. In the presence of DNQX, AP5 and AP3 (a group I metabotropic glutamate receptor (mGluR) antagonist), glutamate depolarized the membrane potential, which was suppressed by PBN. However, oligomycin (a mitochondrial ATP synthase inhibitor) or PPADS (a P2 receptor inhibitor) did not affect the substrates-induced depolarization. These results suggest that mitochondrial substrate-induced ROS in SG neuron directly acts on the postsynaptic neuron, therefore increasing the ion influx via glutamate receptors.

Change in malate dehydrogenase and alpha amylase activities in Rubus fruticosus and Valeriana jatamansi treated granary weevil, Sitophilus granarius

Abstract Poor storage conditions provide favorable environment to stored grain pests for their growth. The bio-pesticides are the best alternatives to synthetic pesticides. Present study was conducted to compare toxicity of Rubus fruticosus and Valeriana jatamansi against granary weevil, Sitophilus granarius and subsequent changes in enzyme activity responsible for grain damage. In current research 5 g of R. fruticosus fruit and V. jatamansi rhizome powders were tested separately against S. granarius, in 50 g wheat whole grains for seven days in comparison with the control. The enzymatic activity of malate dehydrogenase and -amylase was observed in the cellular extracts of S. granarius. The insects were crushed and homogenized in phosphate-buffer solution and centrifuged at 10000 rpm for 5 minutes. For the enzymatic measurement supernatant was tested; the spectrophotometer was adjusted at 340 nm. The reagents were mixed and incubated at 25 °C for five minutes. The cuvettes were placed in the experimental and reference sites of spectrophotometer and recorded the change in absorbance for 3-4 minutes. There was 5.60% and 14.92% reduction in the activity of malate dehydrogenase in R. fruticosus and V. jatamansi, treated insects, respectively. The alpha amylase enzyme activity was 6.82% reduced and 63.63% increase in R. fruticosus and V. jatamansi, treated insects, respectively. Present study addresses that both plant powders are effective against granary weevil by altering enzyme activities so both the plant powders can be used as bio-pesticides against the stored grains pests.

Resumo As más condições de armazenamento proporcionam um ambiente favorável às pragas armazenadas para o crescimento. Os biopesticidas são as melhores alternativas aos pesticidas sintéticos. O presente estudo foi conduzido para comparar a toxicidade de Rubus fruticosus e Valeriana jatamansi contra gorgulhos, Sitophilus granarius e subsequentes alterações na atividade enzimática responsáveis por danos aos grãos. Na pesquisa atual, 5 g de frutos de R. fruticosus e pós de rizoma de V. jatamansi foram testados separadamente contra S. granarius, em 50 g de grãos integrais de trigo por sete dias, em comparação com o controle. A atividade enzimática da malato desidrogenase e -amilase foi observada nos extratos celulares de S. granarius. Os insetos foram esmagados e homogeneizados em solução tampão fosfato e centrifugados a 10000 rpm por 5 minutos. Para a medição enzimática, o sobrenadante foi testado; o espectrofotômetro foi ajustado a 340 nm. Os reagentes foram misturados e incubados a 25 °C por cinco minutos. As cubetas foram colocadas nos locais experimentais e de referência do espectrofotômetro e registradas as alterações na absorbância por 3-4 minutos. Houve redução de 5,60% e 14,92% na atividade da malato desidrogenase em R. fruticosus e V. jatamansi, insetos tratados, respectivamente. A atividade da enzima alfa amilase foi reduzida em 6,82% e aumento de 63,63% em R. fruticosus e V. jatamansi, insetos tratados, respectivamente. O presente estudo aborda que ambos os pós de plantas são eficazes contra o gorgulho do celeiro, alterando as atividades enzimáticas, de modo que ambos os pós de plantas possam ser usados como biopesticidas contra pragas de grãos armazenados.

Brain Region Specificity of Mitochondrial Biogenesis and Bioenergetics Response to Nrf2 Knockdown: A Comparison Among Hippocampus, Prefrontal Cortex and Amygdala of Male Rat Brain

ABSTRACT Nuclear factor (erythroid-derived 2)-like 2 (Nrf2) has been identified as the well-known coordinator of intracellular antioxidant defense system. Herein, we aimed to evaluate the effects of Nrf2 silencing on mitochondrial biogenesis markers peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α), nuclear respiratory factor-1(NRF-1), mitochondrial transcription factor A (TFAM) and cytochrome c as well activities of two enzymes citrate synthase (CS) and malate dehydrogenase (MDH) in three brain regions hippocampus, amygdala, and prefrontal cortex of male Wistar rats. Small interfering RNA (siRNA) targeting Nrf2 was injected in dorsal third ventricle. Next, western blot analysis and biochemical assays were used to evaluation of protein level of mitochondrial biogenesis factors and CS and MDH enzymes activity, respectively. Based on findings, whilst Nrf2-silencing led to notably reduction in protein level of mitochondrial biogenesis upstream PGC-1α in three brain regions compared to the control rats, the level of NRF-1, TFAM and cytochrome c remained unchanged. Furthermore, although Nrf2 silencing increased CS activity, activity of MDH significantly decreased in hippocampus and prefrontal cortex areas. Interestingly, CS and MDH activities in amygdala did not change after Nrf2 knockdown. In conclusion, the present findings highlighted complexity of interaction of Nrf2 and mitochondrial functions in a brain region-specific manner. However, by outlining the exact interaction between Nrf2 and mitochondria, it would be possible to find a new therapeutic strategies for neurological disorders related to oxidative stress.

Chemical constituents in green walnut husks of Juglans regia / 中草药

Objective: To study the chemical constituents in green walnut husks of Juglans regia. Methods: The chemical constituents were separated and purified by silica gel column chromatography and HPLC. Their structures were determined on the basis of spectroscopic analyses. Results: Fifteen compounds were isolated and the structures were identified as epi-dihydrophaseic acid (1), 4-butoxy-5, 8-dihydroxy-3, 4-dihydronaphthalen-1-one (2), 4-ethoxy-5, 8-dihydroxy-3, 4-dihydronaphthalen-1-one (3), myricatomento-genin (4), nodulisporone (5), 5, 8-dihydroxy-4S-methoxy-β-tethalone (6), 5-hydroxy-4-methoxy-α-naphthalen-1-one (7), isosclerone (8), 4, 5, 8-trihydroxy-1, 2, 3, 4-tetrahydronaphthalene-1-one (9), 1-ethyl malate (10), 1-buthyl malate (11), succinic acid (12), ethyl-O-β-D-glucopyranoside (13), 1α, 2α, 4β-trihydroxy-1, 2, 3, 4-tetrahydronaphthalene (14), and L-2-O-methyl-chiroinosicol (15). Conclusion: Compounds 5 and 10-14 are isolated from the green walnut husks of J. regia for the first time, and compounds 1, 4, and 15 are isolated from this plant for the first time.

Ringer's malate solution protects against the intestine's apoptosis caused by hemorrhagic shock in rats / 临床麻醉学杂志

Objective To test the protective effect of a new Ringer's malate solution on intestine's apoptosis caused by hemorrhagic shock in rats.Methods Forty-eight Sprague-Dawley male rats, weighing 280-320 g, were randomly assigned into four groups: sham shock group (group SS), normal saline group (group NS), Ringer's lactate group (group RL) and Ringer's malate (group RM), n=12 each.The group SS was served as control group, the other groups were subjected to 60 min of hemorrhagic shock followed by crystalloid resuscitation.Those rats were sacrificed 3 h after resuscitation.Intestinal tissue was harvested to detect Bcl-2/Bax protein level, the bioactivity of superoxide dismutase (SOD) and malondialdehyde (MDA) level.The level of intestinal cell apotosis was measured using TUNEL method and apoptosis index was calculated.The intestinal histopathology was examined.Results Compared with group SS, the expression of Bcl-2 and the bioactivity of SOD were lower, the level of Bax protein, MDA and apoptotic index were higher in groups NS, RL and RM (P<0.05).Compared with groups NS and RL, the expression of Bcl-2 and the bioactivity of SOD was higher, the level of Bax protein, MDA and apoptotic index were lower in group RM (P<0.05).Histopathological examination showed that group RM was better than group NS and group RL.Conclusion Ringer's malate alleviated intestinal apoptosis caused by hemorrhagic shock in rats.The study suggests that Ringer's malate solution could be a potential new therapeutic agent for fluid resuscitation.

Comparison of liver injury during resuscitation with different crystalloid solutions in a rat model of hemorrhagic shock / 中华麻醉学杂志

Objective To compare the degree of liver injury during resuscitation with different crystalloid solutions in a rat model of hemorrhagic shock.Methods Forty-eight SPF healthy male SpragueDawley rats,aged 7-9 weeks,weighing 280-320 g,were assigned into 4 groups (n=12 each) using a random number table:sham operation group (group S),normal saline group (group NS),Ringer's lactate solution group (group RL) and Ringer's malate solution group (group RM).Hemorrhagic shock was induced by withdrawing blood from the right internal jugular vein until mean arterial pressure was reduced to 35-45 mmHg which was maintained for 1 h.The internal jugular vein and artery were cannulated after anesthetization,but no animals were subjected to hemorrhage in group S.The crystalloid solution (2 times the volume of blood loss) was infused intravenously over 30 min starting from 1 h of shock.The animals were resuscitated with 0.9％ sodium chloride solution in group NS,with Ringer's lactate solution in group RL,and with Ringer's malate solution in group RM.Mean arterial pressure was continuously monitored and recorded during the experiment.Before shock (T1),at 1 h of shock (T2) and at 4 h after resuscitation (T3),blood samples were collected from the right internal jugular vein for determination of serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) concentrations by enzyme-linked immunosorbent assay.Rats were sacrificed at T3,and livers were removed for measurement of malondialdehyde (MDA) content and superoxide dismutase (SOD) activity in liver tissues (using colorimetric method) and for examination of pathological changes of liver tissues (with light microscope).Results Compared with group S,the serum ALT and AST concentrations at T2.3 and SOD activity and MDA content at T3 were significantly increased in NS,RL and RM groups (P＜0.05).Compared with group NS or group RL,the serum ALT and AST concentrations were significantly decreased,the SOD activity was increased,and the MDA content was decreased at T3 (P＜0.05),and the pathological changes of liver tissues were significantly attenuated in group RM.Conclusion Ringer's malate solution produces better efficacy than normal saline and Ringer's lactate solution when used for resuscitation and mitigating liver injury in a rat model of hemorrhagic shock.

Development and validation of a HPTLC method for analysis of Sunitinib malate

ABSTRACT A simple high performance thin layer chromatography (HPTLC) has been developed and validated for determination of sunitinib malate and possible impurities. The samples were applied in forms of bands on an aluminum TLC plate pre-coated with silica gel and were separated using dichloromethane: methanol: toluene: ammonia solution as the mobile phase. Sunitinib malate was thoroughly separated from impurities including E-isomer, sunitinib N-oxide and impurity B with a retention factor (RF) of 0.35±0.02. Quantitative analysis of sunitinib was carried out using a mobile phase consisting of dichloromethane:methanol:ammonia solution, RF value was 0.53±0.02 for Z isomer. Detection was performed densitometrically in absorbance mode at 430 nm. This method was found to produce sharp, symmetrical, and well resolved peaks. Linear relationship with the coefficients of determination > 0.99 was achieved over the concentration range of 27.34 to 437.5 ng/spot. This method provides robust, replicable and accurate results with acceptable sensitivity.

Effect of malate on docosahexaenoic acid production from Schizochytrium sp. B4D1

Background: Malate involves in the citrate/malate and transhydrogenase cycles to provide precursors for docosahexaenoic acid (DHA) synthesis. The optimal strategy was investigated for increasing DHA production in Schizochytrium species during fermentation. Results: DHA production increased by 47% and reached 5.51 g/L when 4 g malate/L was added during the rapid lipid accumulation stage in shake-flasks culture. Inducing effects of malate was further investigated through the analysis of three kinetic parameters, including specificcell growth rate(μ), specific glucose consumption rate (qGlu)and DHA formation rate (qDHA). DHA concentration was enhanced through a novel fed-batch strategy to a maximum value of 30.7 g/L, giving a yield of 0.103 g DHA/g glucose and a productivity of 284 mg L-1 h-1. Conclusion: A novel malate feeding strategy was developed that enhanced DHA yield and productivity of Schizochytrium species which may offer a desirable method for industrial applications.

Militarine alleviates white matter damage and cognitive impairment in rats with chronic cerebral hypoperfusion / 药学学报

Chronic cerebral hypoperfusion is a model for white matter lesions (WMLs) and cognitive impairment. In this study, we used the model in testing the protective effect of (-)-(2R)-1-[(4-β-D-glucopyranosyloxy) benzyl]-4-[4-(β-D-glucopyranosyloxy)benzyl]-2-isobutyl malate (militarine) on the white matter damaged. The model was established by bilateral common carotid ligation. Militarine (10 and 20 mg·kg-1·d-1) or saline was intragastrically administered daily for 30 days following the operation. Militarine (20 mg·kg-1·d-1)-treated rats exhibited significantly shorter escape latency, latency of the first time crossing and more numbers of platform crossings in Morris water maze task. Luxol fast blue (LFB) staining and Western blot analysis indicated that militarine promoted rehabilitation of white matter and increased levels of myelin basic protein (MBP) in the rats. Immunohistochemical staining for 2',3'-cyclic-nucleotide 3'-phosphodiesterase (CNPase) revealed that militarine (20 mg·kg-1·d-1) markedly suppressed loss of CNPase-positive oligodendrocytes in the rat model. In conclusion, militarine can improve WMLs and cognitive impairment in the rat chronic hypoperfusion model.

Molecular cloning, purification and immunogenicity of recombinant Brucella abortus 544 malate dehydrogenase protein

The Brucella mdh gene was successfully cloned and expressed in E. coli. The purified recombinant malate dehydrogenase protein (rMDH) was reactive to Brucella-positive bovine serum in the early stage, but not reactive in the middle or late stage, and was reactive to Brucella-positive mouse serum in the late stage, but not in the early or middle stage of infection. In addition, rMDH did not react with Brucella-negative bovine or mouse sera. These results suggest that rMDH has the potential for use as a specific antigen in serological diagnosis for early detection of bovine brucellosis.

Effect of famitinib malate on adverse reactions by radiotherapy and chemotherapy in treatment of advanced nasopharyngeal carcinoma / 现代临床护理

Objective To investigate effect of famitinib malate on adverse reactions by radiotherapy and chemotherapy in treatment of advanced nasopharyngeal carcinoma and the nursing strategies.Methods From November 2011 to December 2013, 20 cases of advanced nasopharyngeal carcinoma in our hospital were treated with famitinib malate combined with radiotherapy and chemotherapy.During the treatment,we observed the adverse reactions and gave the symptomatic treatment.Results The rates of adverse reactions such as hypertension,renal toxicity,oral mucositis,myelosuppression,gastrointestinal reactions,nasal bleeding, abnormal liver function,and hand-foot skin reaction were 60.0%,70.0%,90.0%,100.0%,85.0%,10.0%,45.0%and 25.0%respectively.After symptomatic treatment,all completed the treatment.Conclusions The incidence rate of adverse reactions of famitinib malate combined with radiotherapy and chemotherapy for treating advanced nasopharyngeal carcinoma is high.Close monitoring and observation during treatment courses can ensure the successful completion of treatment.

Analysis of water quality parameters of River Ganga during Maha Kumbha, Haridwar, India.

This study represents the summary of the water quality of River Ganga during mass bathing in Haridwar during Maha Kumbha of 2010 in terms of microbiological and molecular analysis. The sample was collected from River Ganga during Makar Sankranti to Shakh Poornima and assessed for fecal indicator bacteria Escherichia coli along with Standard Plate Count (SPC) to determine total bacterial load in the river. Of all the nine days of sample collection (mass bathing days) results on the main royal bath (Baisakhi) displayed maximum SPC (log 6.79 cfu ml-1) and most probable number (210 and 150 MPN 100 ml-1 for total and fecal coli form, respectively). The water was extremely contaminated and not suitable for drinking on Somvati Amavasya, Maghi Poornima, Maha Shivratri and Baisakhi. The results clearly indicated that the mass bathing coupled with ritual activities performed by bathers was most probable cause of increased values of different parameters. The polymerase chain reaction analysis targeting malate dehydrogenase (mdh) gene proved to be more rapid and sensitive than classical culture techniques.

Effects of Mitochondrial Reactive Oxygen Species on Neuronal Excitability in Rat Spinal Substantia Gelatinosa Neurons

Recent studies indicate that reactive oxygen species (ROS) are critically involved in persistent pain primarily through spinal mechanisms, and that mitochondria are the main source of ROS in the spinal dorsal horn. To investigate whether mitochondrial ROS can induce changes in membrane excitability on spinal substantia gelatonosa (SG) neurons, we examined the effects of mitochondrial electron transport complex (ETC) substrates and inhibitors on the membrane potential of SG neurons in spinal slices. Application of ETC inhibitors, rotenone or antimycin A, resulted in a slowly developing and slight membrane depolarization in SG neurons. Also, application of both malate, a complex I substrate, and succinate, a complex II substrate, caused reversible membrane depolarization and enhanced firing activity. Changes in membrane potential after malate exposure were more prominent than succinate exposure. When slices were pretreated with ROS scavengers such as phenyl-N-tert-buthylnitrone (PBN), catalase and 4-hydroxy-2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPOL), malate-induced depolarization was significantly decreased. Intracellular calcium above 100 microM increased malateinduced depolarization, witch was suppressed by cyclosporin A, a mitochondrial permeability transition (MPT) inhibitor. These results suggest that enhanced production of spinal mitochondrial ROS can induce nociception through central sensitization.

Hematological adverse events of sunitinib in treatment of advanced renal cell carcinoma / 中华泌尿外科杂志

Objective To evaluate the hematological adverse events of sunitinib in treatment of advanced renal cell carcinoma.Methods Forty-four male patients and 18 female patients were included in this study.They were all with metastatic renal cell carcinoma and received sunitinib treatment at the dose of 50 mg daily in repeated 6 weeks cycle (4 weeks on and 2 weeks off).Toxicity was assessed every cycle with tumor assessments every 2 cycles via CT or PET-CT.Results Fifty patients (80.6％) had experienced treatment-related hematotoxicity,including leucocytopenia,anemia and thrombocytopenia.Severe hematological adverse events ( grade 3 -4 ) occured in 18 patients ( 29.0％ ) and slight events ( grade 1 - 2 ) in others (51.6％).Most of the hematological adverse events were manageable and reversible and treatment-changes (dose reduction,interruption) were necessary in severe cases.Almost half of the dose reduction (9/21,42.9％ ) were owing to hematotoxicity.Conclusions Sunitinib of 50 mg dose on schedule 4/2 is effective and well-tolerated in advanced renal carcinoma patients.Hematological adverse events are frequent in Chinese patients and can be controlled well.

Changes in the oxidative metabolism due to nicotine toxicity in the skeletal muscle fibres of male albino rat.

Nicotine has been reported to induce oxidative stress both in vivo and in vitro. The present study was undertaken to examine the effect of nicotine on oxidative metabolism in skeletal muscle fibre types (Type I & Type II) of male albino rats. The animals were divided into two groups: Group-I (control), and Group-II (experimental). The latter received subcutaneous injections at a dose of 0.5 mg/ kg body weight (Experiment-I), 1 mg/kg body weight (Experiment-II), 5 days/week for a period of 8 weeks. The animals were sacrificed after 24 hours of the last treatment, and skeletal muscle fibres such as soleus (SOL), red vastus (RV) and white vastus (WV) were isolated and analyzed. The activity of lactate dehydrogenase (LDH) increased in nicotine-treated rats of both experiment-I, and experiment-II. Succinate dehydrogenase (SDH), isocitrate dehydrogenase (ICDH), malate dehydrogenase (MDH) and glucose-6-phosphate dehydrogenase (G-6-PDH) were decreased in soleus (SOL), red vastus (RV) and white vastus (WV) skeletal muscle fibres. These findings indicate nicotine-induced oxidative stress in the skeletal muscle fibres of male albino rats.

Effect of glutamine on the mRNA level of key enzymes of malate-aspartate shuttle in the rat intestine subjected to ischemia reperfusion / Efeito da glutamina sobre o nível de RNA Mensageiro das enzimas-chave do ciclo malato-aspartato no intestino de ratos submetidos à isquemia e reperfusão

PURPOSE: To determine the effects of oral L-glutamine (L-Gln) and the dipeptide l-alanyl-glutamine (L-Ala-Gln) upon the activity of the malate-aspartate shuttle in the rat distal small intestine following ischemia and reperfusion. METHODS: Seventy-two Wistar rats (350-400g), were randomized in 2 groups (n = 36): group S (Sham) and Group T (Treatment) and divided into 12 subgroups (n = 6): A-A6, and B1-B6. The subgroups A1-A3 were subjected to sham procedures at 30 and 60 minutes. Thirty minutes before the study, rats were treated with calcium caseinate, 0.5g/Kg (subgroups A1, A4, B1, B4), L-Gln, 0.5g / kg (subgroups A2, A5, B2 and B5) or L-Ala-Gln, 0.75g/Kg (subgroups A3, A6, B3, B6), administered by gavage. Ischemia was achieved by clamping the mesenteric vessels, delimiting a segment of bowel 5 cm long and 5 cm apart from the ileocecal valve. Samples were collected 30 and 60 minutes after start of the study for real-time PCR assay of malate dehydrogenases (MDH1-2) and aspartate-aminotransferases (GOT1-2) enzymes. RESULTS: Tissue MDH and GOT mRNA expression in intestinal samples from rats preconditioned with either L-Gln or L-Ala-Gln showed no significant differences both during ischemia and early reperfusion. CONCLUSION: Activation of the malate-aspartate shuttle system appears not to be the mechanism of glutamine-mediated elevation of glucose oxidation in rat intestine during ischemia/reperfusion injury.

OBJETIVO: Determinar os efeitos da administração oral de L-glutamina (L-Gln) e do dipeptídeo L-alanil-glutamina (L-Ala-Gln) sobre a atividade do ciclo malato-aspartato no intestino delgado distal de ratos após isquemia/reperfusão. MÉTODOS: Setenta e dois ratos Wistar (350-400g) foram randomizados em 2 grupos (n = 36): T grupo S (Sham) e grupo (Tratamento) e distribuídos em 12 subgrupos (n = 6): A-A6, e B1-B6. Os subgrupos A1-A3 foram submetidos a procedimentos "sham" aos 30 e 60 minutos. Trinta minutos antes do estudo, os ratos foram tratados com caseinato de cálcio, 0,5 g/kg (subgrupos A1, A4, B1 e B4), L-Gln, 0,5 g/kg (subgrupos A2, A5, B2 e B5) ou L-Ala -Gln, 0,75g/kg (subgrupos A3, A6, B3, B6), administrado por gavagem. A isquemia foi obtida por pinçamento dos vasos mesentéricos, delimitando um segmento do intestino cinco centímetros de comprimento e 5 cm da válvula ileocecal. Amostras foram coletadas aos 30-60 minutos para ensaio de PCR em tempo real das enzimas malato desidrogenases (MDH1-2), aspartato-aminotransferase (GOT1-2). RESULTADOS: A expressão de MDH e GOT mRNA nas amostras provenientes do intestino delgado de ratos pré-condicionados com L-Gln ou L-Ala-Gln não apresentou diferenças significativas, tanto durante a isquemia como na fase inicial de reperfusão. CONCLUSÃO: Ativação do ciclo malato-aspartato não parece ser o mecanismo de elevação glutamina-mediada da oxidação da glicose no intestino de ratos durante a isquemia / reperfusão.

Therapeutic potential of sunitinib in the treatment of malignant islet cell tumor / 中华内分泌代谢杂志

Malignant islet cell tumor, a rare type of neuroendocrine carcinoma, biologically behaves in an aggressive way and is difficulty to be treated. Sunitinib malate, a novel tyrosine kinase inhibitor, demonstrates a high efficacy in treating malignant islet cell tumor as shown by promising results in recent trials.