Correlation of acetylcholinesterase activity in the brain and blood of wistar rats acutely infected with Trypanosoma congolense

ObjectiveTo investigate the neurotransmitter enzyme Acetylcholinesterase (AChE) activity in the brain and blood of rats infected with Trypanosoma congolense (T. congo).MethodsPresence and degree of parasitemia was determined daily for each rat by the rapid matching method. AChE activity was determined by preparing a reaction mixture of brain homogenate and whole blood with 5, 5-dithiobisnitrobenzioc acid (DTNB or Ellman's reagent) and Acetylthiocholine (ATC). The increase in absorbance was recorded at 436 nm over 10 min at 2 min intervals. Trypanosome species identification (before inoculation and on day 10 post infection) was done by Polymerase chain reaction using specific primers.ResultsThe AChE activity in the brain and blood decreased significantly as compared with the uninfected control. The AChE activity dropped to 0.32 from 2.20 μmol ACTC min^?1mg protein^?1 in the brain and 4.57 to 0.76 μmol ACTC min-1mg protein^?1 in the blood. The animals treated with Diminaveto at 3.5 mg/kg/d were observed to have recovered significantly from parasitemia and were able to regain AChE activity in the blood but not in the brain as compared to the control groups. We also observed, that progressive parasitemia resulted to alterations in PCV, Hb, RBC, WBC, neurophils, total protein, lymphocytes, monocytes and eosinophil in acute infections of T. congo. Polymerase chain reaction (PCR) of infected blood before inoculation and on day 10 post infection revealed 600 bp on agarose gel electrophoresis.ConclusionsThis finding suggest that decrease in AChE activity increases acetylcholine concentration in the synaptic cleft resulting to neurological failures in impulse transfer in T. congo infection rats.     

铅对作业工人甲状腺功能的影响

目的　了解铅对作业工人甲状腺功能的影响。方法　选择暴露于铅作业环境下的人群 ,了解工人作业工龄 ,采用火焰原子吸收光谱法测定其作业环境中铅浓度 ,用原子吸收光谱法测定作业工人血铅 (PbB)浓度 ,用血液锌原卟啉测定仪测定血锌原卟啉 (ZPP)浓度 ,用放射免疫分析法检测血清中促甲状腺素 (TSH)、三碘甲状腺原氨酸 (T3)、甲状腺素 (T4 )、游离T3(FT3)、游离T4 (FT4 ) 5项甲状腺功能指标。结果　血铅 >2 .88μmol/L时 ,T3[(1 .54± 0 .39)nmol/L]、FT3[(5 .50± 1 .2 6)pmol/L]含量明显低于血铅 (1 .92～ 2 .88) μmol/L组 [T3(1 .71± 0 .45)nmol/L、FT3(6 .1 2± 1 .64)pmol/L] ,差异有显著性(P <0 .0 5)。铅作业工龄长短对甲状腺激素 (TH)含量未见明显影响。结论　高浓度血铅可能抑制了T4 的脱碘 ;铅作业工龄对甲状腺功能未见明显影响     

Core-peripheral temperature gradient in children: does it reflect clinically important changes in circulatory haemodynamics?

Following open heart surgery, changes in core and peripheral skin temperature and changes in the core-peripheral temperature gradient were measured in 10 children. These were correlated with changes in cardiac index, systemic vascular resistance index, mean arterial pressure and urinary output. During the study intervals, which lasted 1 h each, no changes in medical management were made. Using Spearman's rank correlation, only a change in central venous pressure was found to correlate with a change in the core-peripheral temperature gradient. We conclude that a change in the core-peripheral temperature will give valuable information about the patient's intravascular volume.     

Binding of the phytotoxin zinniol stimulates the entry of calcium into plant protoplasts

Zinniol [1,2-bis(hydroxymethyl)-3-methoxy-4-methyl-5-(3-methyl-2-butenyloxy)benzene], a toxin produced by fungi of the Alternaria group, causes symptoms in plants that resemble those induced by the fungi. The phytotoxin binds to carrot protoplasts and isolated membranes in a saturable and reversible manner. Receptor occupancy stimulates entry of calcium into protoplasts. Zinniol can partially reverse the effects and binding of the calcium-channel blockers desmethoxyverapamil and bepridil. Selected cell lines that are insensitive to zinniol lose part of their binding capacity and sensitivity to the action of the agonist-like compound but are still able to bind calcium-channel blockers. We conclude that zinniol acts on calcium entry but that the targets of the toxin and of calcium-channel blockers are dissimilar, suggesting the occurrence of sites affected both by zinniol and by channel blockers and of sites affected only by zinniol.     

A patenting perspective on human neutrophil elastase (HNE) inhibitors (2014-2018) and their therapeutic applications

Introduction: Human neutrophil elastase (HNE) is involved in a variety of serious chronic diseases, especially cardiopulmonary pathologies. For this reason, the regulation of HNE activity represents a promising therapeutic approach, which is evident by the development of a number of new and selective HNE inhibitors, both in the academic and pharmaceutical environments.

Areas covered: The present review analyzes and summarizes the patent literature regarding human neutrophil elastase inhibitors for the treatment of cardiopulmonary diseases over 2014–2018.

Expert opinion: HNE is an interesting and defined target to treat various inflammatory diseases, including a number of cardiopulmonary pathologies. The research in this field is quite active, and a number of HNE inhibitors are currently in various stages of clinical development. In addition, new opportunities for HNE inhibitor development stem from recent studies demonstrating the involvement of HNE in many other inflammatory pathologies, including rheumatoid arthritis, inflammatory bowel disease, skin diseases, and cancer. Furthermore, the development of dual HNE/proteinase 3 inhibitors is being pursued as an innovative approach for the treatment of neutrophilic inflammatory diseases. Thus, these new developments will likely stimulate new and increased interest in this important therapeutic target and for the development of novel and selective HNE inhibitors.