The cell and molecular basis of mechanical, cold, and inflammatory pain

Peripheral pain pathways are activated by a range of stimuli. We used diphtheria toxin to kill all mouse postmitotic sensory neurons expressing the sodium channel Nav1.8. Mice showed normal motor activity and low-threshold mechanical and acute noxious heat responses but did not respond to noxious mechanical pressure or cold. They also showed a loss of enhanced pain responses and spontaneous pain behavior upon treatment with inflammatory insults. In contrast, nerve injury led to heightened pain sensitivity to thermal and mechanical stimuli indistinguishable from that seen with normal littermates. Pain behavior correlates well with central input from sensory neurons measured electrophysiologically in vivo. These data demonstrate that Na(v)1.8-expressing neurons are essential for mechanical, cold, and inflammatory pain but not for neuropathic pain or heat sensing.     

Neoechinulin A as a Promising SARS-CoV-2 Mpro Inhibitor: In Vitro and In Silico Study Showing the Ability of Simulations in Discerning Active from Inactive Enzyme Inhibitors

The COVID-19 pandemic and its continuing emerging variants emphasize the need to discover appropriate treatment, where vaccines alone have failed to show complete protection against the new variants of the virus. Therefore, treatment of the infected cases is critical. This paper discusses the bio-guided isolation of three indole diketopiperazine alkaloids, neoechinulin A (1), echinulin (2), and eurocristatine (3), from the Red Sea-derived Aspergillus fumigatus MR2012. Neoechinulin A (1) exhibited a potent inhibitory effect against SARS-CoV-2 M^pro with IC₅₀ value of 0.47 μM, which is comparable to the reference standard GC376. Despite the structural similarity between the three compounds, only 1 showed a promising effect. The mechanism of inhibition is discussed in light of a series of extensive molecular docking, classical and steered molecular dynamics simulation experiments. This paper sheds light on indole diketopiperazine alkaloids as a potential structural motif against SARS-CoV-2 M^pro. Additionally, it highlights the potential of different molecular docking and molecular dynamics simulation approaches in the discrimination between active and inactive structurally related M^pro inhibitors.     

Tyrosine Ameliorates Some of the Clinical,Biochemical and Haematological Effects of Acute Stress Associated with Transportation of Desert Sheep

We studied some clinical, biochemical and haematological variables in Desert (Najdi) sheep acutely stressed in the course of individual road transportation, and the influence thereon of pretreatment with tyrosine. Transportation for 30 min resulted in variable but statistically insignificant increases in heart, pulse and respiratory rates. It also caused significant increases in the plasma concentration of cortisol (from 43.5 to 101.7 mmol/L) and glucose (from 3.1 to 4.5 mmol/L), and a decrease in that of magnesium (from 0.85 to 0.72 mmol/L). The endogenous thiocyanate level was unaffected. The transportation stress also decreased the haematocrit (PCV) and the number of lymphocytes, and increased the concentration of haemoglobin. Pretreatment of sheep with tyrosine at a dose of 100 mg/kg by the intravenous route significantly ameliorated the stress-induced clinical, biochemical and haematological changes. The treatment caused no overt adverse effects.     

Inhibin and reproduction. First communication: changes to inhibin level in Barki ewes after artificial infection with bluetongue virus

Bluetongue virus type 16, isolated from sheep in Egypt, was injected to 4 normally cycling Barki ewes and caused high levels of inhibin. This was assayed by a biological method, using suppression of the luteinising hormone (LH) of castrated rats. Albumin (fraction 2) was injected to normally cycling ewes. The sera of injected ewes were investigated 1 day after injection and weekly up to the 4th one injection. There was a gradual decrease of LH (4.8 +/- 0.52 I.U./ml serum) until the minimum level (1.17 +/- 0.25 I.U./ml serum) was reached, in comparison to the control serum LH which was 5.26 +/- 0.52 I.U./ml serum during the dioestrous phase.     

Concentrations of trace minerals in the spinal cord of horses with equine motor neuron disease

OBJECTIVE: To compare concentrations of trace minerals in the spinal cord of horses with equine motor neuron disease (EMND) with those of horses without neurologic disease (control horses). ANIMALS: 24 horses with EMND and 22 control horses. PROCEDURE: Spinal cord trace mineral concentrations in horses with EMND and control horses were analyzed by use of inductively coupled plasma atomic emission spectroscopy (calcium, phosphorus, sodium, potassium, magnesium, copper, iron, manganese, nickel, zinc, aluminum, cobalt, and chromium), atomic absorption spectrophotometry (lead and cadmium), flameless atomic absorption (mercury), and fluorometry (selenium). RESULTS: Copper concentration was significantly higher in the spinal cord of horses with EMND, compared with control horses; spinal cord concentrations of all other trace minerals were similar between groups. CONCLUSION AND CLINICAL RELEVANCE: Among spinal cord trace minerals investigated in the study, only copper concentrations were significantly different between horses with EMND and horses without neurologic disease, which suggests that copper may be involved in the pathogenesis of EMND. An hypothesis of oxidative injury in this disease is supported by the finding of increased copper concentrations in the spinal cord and by low vitamin E concentrations reported by other researchers.     

龙胆泻肝汤药理学与毒理学研究进展

龙胆泻肝汤为中医经典名方,源于清代汪昂《医方集解》,由龙胆草、黄芩、栀子、柴胡、当归、生地黄、木通、车前子、泽泻、甘草10味组成[1]。由于其疗效显著,在临床上被广泛应用。近年来对其药理学、毒理学进行了广泛研究,取得了可喜成绩。1药理学研究1.1中兽医药理论龙胆泻肝汤是以“凉肝猛将”大苦大寒的龙胆草为君,上清肝胆实火,下利三焦湿热,泻火除湿两擅其功;臣以黄芩、栀子泻火;泽泻、木通、车前子除湿,使邪出有路;佐以生地、当归养血益阴,使祛邪不伤正,燥湿不伤阴,并用柴胡疏畅肝胆。综观全方,泻中有补,利中有滋,降中寓升,祛邪不伤正,…     

银合欢落叶层对苗圃生长的森林一农田作物的他感作用(英文)

利用随机区组试验评估了孟加拉国吉大港大学苗圃内的银合欢落叶对森林作物种白格、黄金檀和农田作物种长豇豆、鹰嘴豆和木豆的他感作用。结果表明,凋落叶诱导抑制作物的萌发和生长,该抑制作用依赖于萃取物浓度、凋落物及受体物种类型。萃取物浓度越高则他感作用越强。受体植物的生长响应随应用的凋落叶而变化。低浓度(10g·m-2)凋落叶对农田作物嫩芽生长有促进作用,而其他浓度的凋落叶则呈现明显的抑制作用,施用的凋落叶浓度越大抑制作用也越大。但是不同处理所表现出的抑制趋势并不均一,根系生长受到的影响大于嫩芽。图3表4参34。