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).     

Human Milk Lactose,Insulin, and Glucose Relative to Infant Body Composition during Exclusive Breastfeeding

Human milk (HM) components may influence infant growth and development. This study aimed to investigate relationships between infant body composition (BC) and HM lactose, insulin, and glucose (concentrations and calculated daily intakes (CDI)) as well as 24-h milk intake and maternal BC at 3 months postpartum. HM samples were collected at 2 months postpartum. Infant and maternal BC was assessed with bioimpedance spectroscopy. Statistical analysis used linear regression accounting for infant birth weight. 24-h milk intake and CDI of lactose were positively associated with infant anthropometry, lean body mass and adiposity. Higher maternal BC measures were associated with lower infant anthropometry, z-scores, lean body mass, and adiposity. Maternal characteristics including BC and age were associated with concentrations and CDI of HM components, and 24-h milk intake. In conclusion, 24-h intake of HM and lactose as well as maternal adiposity are related to development of infant BC.     

A simulation study comparing tests for the equality of coefficients of variation

The coefficient of variation is commonly used in medical and biological sciences. In this paper, several parametric and non-parametric tests for the equality of coefficients of variation in k populations are reviewed. Simulation studies are conducted to compare the sizes and power of these tests. It is found that the parametric tests perform well if the data are normally distributed, but perform poorly if otherwise. The non-parametric test, however, is rather robust against the underlying distribution. An example using data of the Quality Assurance Program from the Hong Kong Medical Technology Association in Haematology and Serology is provided. The insensitivity of the non-parametric test to outliers is demonstrated. © 1998 John Wiley & Sons, Ltd.     

Racial variation in incidence of trisomy 21: Survey of 57,742 Chinese deliveries

The objective of this study was to establish whether the influence of advanced maternal age on the incidence of trisomy 21 in the local Chinese population is similar to that seen among European patients by comparing the observed number of trisomy 21 cases against the expected number which was calculated from age-specific Caucasian data and adjusted for intrauterine lethality and rate of amniocentesis. The obstetric and neonatal data of 57,742 pregnancies in ethnic Chinese were reviewed, of which 10.5% were from mothers age 35 or over. A total of 74 cases of trisomy 21 was detected (overall incidence of 1.28 per 1,000 deliveries). The expected number of trisomy 21 cases in mothers younger than 35 was 45.6, which was similar to the observed number of 43. Among mothers age 35 or above, the expected and observed numbers of cases were 38.52 and 31, respectively, again a difference not statistically significant. Therefore we conclude that there is no significant racial variation in the incidence of trisomy 21, both in the younger and older age groups, when comparing Chinese to Caucasian populations. Am. J. Med. Genet. 75:386-388, 1998. © 1998 Wiley-Liss, Inc.     

Photo-activated pheophorbide-a, an active component of Scutellaria barbata, enhances apoptosis via the suppression of ERK-mediated autophagy in the estrogen receptor-negative human breast adenocarcinoma cells MDA-MB-231

Aim of the study

Scutellaria barbata is a traditional Chinese medicine for cancer treatments. Pheophorbide-a (Pa), one of the active components isolated from this herbal medicine has been proposed to be a potential natural photosensitizer for photodynamic therapy. The anti-tumor effect of pheophorbide-a based photodynamic therapy (Pa-PDT) has been successfully demonstrated in a wide range of human malignant cell lines. However, the effectiveness of Pa-PDT has not yet been evaluated on human breast cancer, which is documented as the second common and the fifth most lethal cancer worldwide.

Materials and methods

The cytotoxicity of Pa-PDT was evaluated by using an estrogen receptor (ER)-negative human breast adenocarcinoma cell line MDA-MB-231. The involvement of mitochondria was revealed by the change of mitochondrial membrane potential and the increase of intracellular reactive oxygen species (ROS). The hallmarks of apoptosis, ER stress and autophagy were also assessed by DNA fragmentation, Western blotting, and immunostaining assays.

Results

Pa-PDT showed inhibitory effect on the growth of MDA-MB-231 cells with an IC₅₀ value of 0.5 μM at 24 h. Mitogen-activated protein kinase (MAPK) pathway was found to be triggered, where activation of c-Jun N-terminal kinase (JNK) and inhibition of extracellular signal-regulated kinase (ERK) were occurred in the Pa-PDT-treated cells. Our findings suggested that Pa-PDT exhibited its anti-tumor effects by the activation of mitochondria-mediated apoptosis and the ERK-mediated autophagy in MDA-MB-231 cells.

Conclusion

The present study suggested Pa-PDT is a potential protocol for the late phase human breast cancer, and it is the first study to demonstrate the Pa-PDT induced autophagy contributed to the anti-tumor effects of Pa-PDT on human cancer cells.     

Racial disparities in family-provider interactions for pediatric asthma care

Objective: Black and Latino children experience significantly worse asthma morbidity than their white peers for multifactorial reasons. This study investigated differences in family-provider interactions for pediatric asthma, based on race/ethnicity. Methods: This was a cross-sectional study of parent surveys of asthmatic children within the Population-Based Effectiveness in Asthma and Lung Diseases Network. Our study population comprised 647 parents with survey response data. Data on self-reported race/ethnicity of the child were collected from parents of the children with asthma. Outcomes studied were responses to the questions about family-provider interactions in the previous 12 months: (1) number of visits with asthma provider; (2) number of times provider reviewed asthma medications with patient/family; (3) review of a written asthma treatment plan with provider; and (4) preferences about making asthma decisions. Results: In multivariate adjusted analyses controlling for asthma control and other co-morbidities, black children had fewer visits in the previous 12 months for asthma than white children: OR 0.63 (95% CI 0.40, 0.99). Additionally, black children were less likely to have a written asthma treatment plan given/reviewed by a provider than their white peers, OR 0.44 (95% CI 0.26, 0.75). There were no significant differences by race in preferences about asthma decision-making nor in the frequency of asthma medication review. Conclusion: Black children with asthma have fewer visits with their providers and are less likely to have a written asthma treatment plan than white children. Asthma providers could focus on improving these specific family-provider interactions in minority children.     

Biophysical modeling of neural plasticity induced by transcranial magnetic stimulation

Transcranial magnetic stimulation (TMS) is a widely used noninvasive brain stimulation method capable of inducing plastic reorganisation of cortical circuits in humans. Changes in neural activity following TMS are often attributed to synaptic plasticity via process of long-term potentiation and depression (LTP/LTD). However, the precise way in which synaptic processes such as LTP/LTD modulate the activity of large populations of neurons, as stimulated en masse by TMS, are unclear. The recent development of biophysical models, which incorporate the physiological properties of TMS-induced plasticity mathematically, provide an excellent framework for reconciling synaptic and macroscopic plasticity. This article overviews the TMS paradigms used to induce plasticity, and their limitations. It then describes the development of biophysically-based numerical models of the mechanisms underlying LTP/LTD on population-level neuronal activity, and the application of these models to TMS plasticity paradigms, including theta burst and paired associative stimulation. Finally, it outlines how modeling can complement experimental work to improve mechanistic understandings and optimize outcomes of TMS-induced plasticity.     

Does 22q11.2 deletion syndrome contribute to the genetic aetiology of Parkinson’s disease?

Journal of Neurology -     

Anti-N-methyl-d-aspartate receptor encephalitis in children: Incidence and experience in Hong Kong

Aim

The study aims to analyze the incidence, clinical features, investigation findings and treatment outcomes of anti-N-methyl-d-aspartate receptor encephalitis in children from Hong Kong.