Video-fluoroscopic study of swallowing in children with neurodevelopmental disorders

BACKGROUND: Children with neurodevelopmental disorders can have feeding problems. Malnutrition and recurrent aspiration pneumonia can increase the risk of morbidity and mortality. Video-fluoroscopic study of swallowing (VFSS) is essential in understanding the pathological mechanisms involved during swallowing. METHODS: The aim of the present study was to assess the role of VFSS in assessment and management of four children with various neurodevelopmental disorders in a multidisciplinary feeding team. We describe the team approach, with the participation of child neurologist, radiologist with the rehabilitation team including the speech therapist, occupational therapist and dietician, in the assessment and plan of management. RESULTS: Video-fluoroscopic study of swallowing had been useful in assessing the type of swallowing problems with treatment goals targeted to the basic underlying pathophysiological mechanism. CONCLUSION: A child neurologist should be involved in the multidisciplinary oromotor rehabilitation program for neurologically impaired children with feeding problems.     

Cholinesterase inhibition by potato glycoalkaloids slows mivacurium metabolism

BACKGROUND: The duration of action for many pharmaceutical agents is dependent on their breakdown by endogenous hydrolytic enzymes. Dietary factors that interact with these enzyme systems may alter drug efficacy and time course. Cholinesterases such as acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) hydrolyze and inactivate several anesthetic drugs, including cocaine, heroin, esmolol, local ester anesthetics, and neuromuscular blocking drugs. Natural glycoalkaloid toxins produced by plants of the family Solanaceae, which includes potatoes and tomatoes, inhibit both AChE and BuChE. Here the authors assess the extent to which two solanaceous glycoalkaloids (SGAs), alpha-solanine and alpha-chaconine, can alter the effects of neuromuscular blocking drugs and cholinesterase inhibitors in vivo and in vitro. METHODS: Inhibition of purified human AChE and BuChE by SGAs, neuromuscular blocking drugs, and cholinesterase inhibitors was assessed by an in vitro colorimetric cholinesterase assay. In vivo experiments were carried out using anesthetized rabbits to test whether SGAs affect recovery from mivacurium-induced paralysis. RESULTS: SGAs inhibited human BuChE at concentrations similar to those found in serum of individuals who have eaten a standard serving of potatoes. Coapplication of SGAs (30-100 nm) with neuromuscular blocking drugs and cholinesterase inhibitors produced additive cholinesterase inhibition. SGA administration to anesthetized rabbits inhibited serum cholinesterase activity and mivacurium hydrolysis. In addition, SGA prolonged the time needed for recovery from mivacurium-induced paralysis (149 +/- 12% of control; n = 12). CONCLUSIONS: These findings support the hypothesis that inhibition of endogenous enzyme systems by dietary factors can influence anesthetic drug metabolism and duration of action. Diet may contribute to the wide variation in recovery time from neuromuscular blockade seen in normal, healthy individuals.     

Evaluation of the sub-acute toxicity of the sclerotium of Lignosus rhinocerus (Cooke), the Tiger Milk mushroom

Ethnopharmacological relevance

Lignosus rhinocerus (known locally as ‘Tiger Milk mushroom’) is the most important medicinal mushroom used by the indigenous communities of Malaysia to treat fever, cough, asthma, cancer, food poisoning and as a general tonic. The sclerotium of the mushroom is the part with medicinal value. Lignosus rhinocerus was hitherto unexploited commercially because of limited supply. Recently, the mushroom was successfully cultivated.

Materials and methods

Sprague Dawley rats (5 rats/group/sex) were fed orally with 250, 500 and 1000 mg/kg TM02, 1000 mg/kg TM03 as well as 1000 mg/kg wild type Lignosus rhinocerus sclerotial powder. Sclerotial powder was orally administered once daily and consecutively for 28 days. Body weight of each animal was measured and any gross behavioral change was observed daily. Hematological and clinical biochemical parameters as well as histopathological analysis were carried out on 29th day.

Results

The results showed that oral administration of the sclerotial powder at daily dose of up to 1000 mg/kg had no adverse effect on the growth rate, hematological and clinical biochemical parameters (including renal and liver function parameters). Histological studies showed that the treatments did not induce any pathological changes in the liver, kidney, heart, spleen and lung of the animals.

Conclusion

In conclusion, our results show that there was no treatment-related sub-acute toxicity in rats following 28-days oral administration of 250, 500 and 1000 mg/kg TM02, 1000 mg/kg TM03 as well as 1000 mg/kg wild type Lignosus rhinocerus sclerotial powder. As the highest tested dose of 1000 mg/kg was not associated with any toxicity concern, the NOAEL dose is higher than 1000 mg/kg.     

Mechanisms of the dilator action of the Erigerontis Herba on rat aorta

Ethnopharmacological relevance

Erigerontis Herba is widely used as a traditional Chinese medicine and is commonly used for neuroprotection and vascular protection.

Aim of study

In this study, the vasodilator effects of Erigerontis Herba (DZXX) were investigated using rat isolated aorta rings.

Material and method

The involvement of endothelium in the vasorelaxation was studied by comparing response of endothelium-intact and endothelium-denuded aorta rings which precontracted with U46619. The involvement of K⁺ channels was studied by pretreatment of the aorta rings with various K⁺ channel inhibitors. The involvement of Ca²⁺ channel was studied by incubating aorta rings with Ca²⁺-free solution, primed with U46619 prior to elicit contraction by addition of Ca²⁺ solution.

Results

DZXX (0.2–2 mg/ml) induced a concentration-dependent relaxation on U44619-precontracted aorta rings with EC₅₀ of 0.354±0.036 mg/ml. Removal of endothelium or pretreatment with a BK_Ca inhibitor iberiotoxin, K_IR inhibitor barium chloride or K_v inhibitor 4-aminopyridine produced no effect on the DZXX-induced vasorelaxation. However, pretreatment with a K_ATP inhibitor glibenclamide or a non-selective K⁺ channel inhibitor tetraethylammonium produced significant inhibition on the DZXX-induced vasorelaxation by 29.9% and 21.3%, respectively. Pretreatment with DZXX (0.4, 1.2 and 2 mg/ml) produced a concentration-dependent inhibition on Ca²⁺-induced vasoconstriction.

Conclusions

These results suggest that the vasodilator effect of DZXX was endothelium-independent, mediated by decreasing the influx of Ca²⁺ by calcium channel inhibition and increasing the influx of K⁺ by opening of a K_ATP channel.     

Correction: Discovery of 8-prenylnaringenin from hop (Humulus lupulus L.) as a potent monoacylglycerol lipase inhibitor for treatments of neuroinflammation and Alzheimer’s disease

Correction for ‘Discovery of 8-prenylnaringenin from hop (Humulus lupulus L.) as a potent monoacylglycerol lipase inhibitor for treatments of neuroinflammation and Alzheimer’s disease’ by Min-Che Tung et al., RSC Adv., 2021, 11, 31062–31072, https://doi.org/10.1039/D1RA05311F.

The authors regret that the name of one of the authors (Hsing-Mien Hsu) was shown incorrectly in the original article. The corrected author list is as shown above.The authors also regret an incorrect version of Fig. 7 was included in the original article. The correct version of Fig. 7 is presented below.Open in a separate windowFig. 7The dose-dependent inhibitions of the identified inhibitors against hMAGL.The Royal Society of Chemistry apologises for these errors and any consequent inconvenience to authors and readers.     

Cyclopeptide RA-V inhibits angiogenesis by down-regulating ERK1/2 phosphorylation in HUVEC and HMEC-1 endothelial cells

BACKGROUND AND PURPOSE

Anti-angiogenic agents have recently become one of the major adjuvants for cancer therapy. A cyclopeptide, RA-V, has been shown to have anti-tumour activities. Its in vitro anti-angiogenic activities were evaluated in the present study, and the underlying mechanisms were also assessed.

EXPERIMENTAL APPROACH

Two endothelial cell lines, human umbilical vein endothelial cells (HUVEC) and human microvascular endothelial cells (HMEC-1), were used. The effects of RA-V on the proliferation, cell cycle phase distribution, migration, tube formation and adhesion were assessed. Western blots and real-time PCR were employed to examine the protein and mRNA expression of relevant molecules.

KEY RESULTS

RA-V inhibited HUVEC and HMEC-1 proliferation dose-dependently with IC₅₀ values of 1.42 and 4.0 nM respectively. RA-V inhibited migration and tube formation of endothelial cells as well as adhesion to extracellular matrix proteins. RA-V treatment down-regulated the protein and mRNA expression of matrix metalloproteinase-2. Regarding intracellular signal transduction, RA-V interfered with the activation of ERK1/2 in both cell lines. Furthermore, RA-V significantly decreased the phosphorylation of JNK in HUVEC whereas, in HMEC-1, p38 MAPK was decreased.

CONCLUSIONS AND IMPLICATIONS

RA-V exhibited anti-angiogenic activities in HUVEC and HMEC-1 cell lines with changes in function of these endothelial cells. The underlying mechanisms of action involved the ERK1/2 signalling pathway. However, RA-V may regulate different signalling pathways in different endothelial cells. These findings suggest that RA-V has the potential to be further developed as an anti-angiogenic agent.     

Effects of Cordyceps sinensis, Cordyceps militaris and their isolated compounds on ion transport in Calu-3 human airway epithelial cells

AIM OF THE STUDY: The traditional Chinese medicine Cordyceps sinensis (CS) (Clavicipitaceae) improves pulmonary function and is used to treat respiratory disease. Here, we compare the efficacy and mechanisms of action of Cordyceps sinensis and Cordyceps militaris (CM) (Clavicipitaceae) in Calu-3 human airway epithelial monolayer model. MATERIAL AND METHODS: The extracts of Cordyceps sinensis and Cordyceps militaris, as well as their isolated compounds, cordycepin and adenosine, stimulated ion transport in a dose-dependent manner in Calu-3 monolayers. In subsequent experiments, transport inhibitor bumetanide and carbonic anhydrase inhibitor acetazolamide were added after Cordyceps sinensis and Cordyceps militaris extracts to determine their effects on Cl- and HCO3- movement. RESULTS: The results suggested that Cordyceps sinensis and Cordyceps militaris extracts may affect the anion movement from the basolateral to apical compartments in the airway epithelia. CONCLUSIONS: Basolateral Na+-K+-2Cl- cotransporter and apical cAMP-dependent cystic fibrosis transmembrane conductance regulator Cl- channel are involved in the process. The results provide the first evidence for the pharmacological mechanism of Cordyceps sinensis and Cordyceps militaris on respiratory tract.     

Immunomodulatory and anti-SARS activities of Houttuynia cordata

BACKGROUND: Severe acute respiratory syndrome (SARS) is a life-threatening form of pneumonia caused by SARS coronavirus (SARS-CoV). From late 2002 to mid 2003, it infected more than 8000 people worldwide, of which a majority of cases were found in China. Owing to the absence of definitive therapeutic Western medicines, Houttuynia cordata Thunb. (Saururaceae)(HC) was shortlisted by Chinese scientists to tackle SARS problem as it is conventionally used to treat pneumonia. AIM OF THE STUDY: The present study aimed to explore the SARS-preventing mechanisms of HC in the immunological and anti-viral aspects. RESULTS: Results showed that HC water extract could stimulate the proliferation of mouse splenic lymphocytes significantly and dose-dependently. By flow cytometry, it was revealed that HC increased the proportion of CD4(+) and CD8(+) T cells. Moreover, it caused a significant increase in the secretion of IL-2 and IL-10 by mouse splenic lymphocytes. In the anti-viral aspect, HC exhibited significant inhibitory effects on SARS-CoV 3C-like protease (3CL(pro)) and RNA-dependent RNA polymerase (RdRp). On the other hand, oral acute toxicity test demonstrated that HC was non-toxic to laboratory animals following oral administration at 16 g/kg. CONCLUSION: The results of this study provided scientific data to support the efficient and safe use of HC to combat SARS.