Investigation of the Adrenergic and Opioid Binding Affinities, Metabolic Stability, Plasma Protein Binding Properties, and Functional Effects of Selected Indole-Based Kratom Alkaloids.

Selected indole-based kratom alkaloids were evaluated for their opioid and adrenergic receptor binding and functional effects, in vivo antinociceptive effects, plasma protein binding, and metabolic stability. Mitragynine, the major alkaloid in Mitragyna speciosa (kratom), had higher affinity at opioid receptors than at adrenergic receptors while the vice versa was observed for corynantheidine. The observed polypharmacology of kratom alkaloids may support its utilization to treat opioid use disorder and withdrawal.

Simultaneous quantification of ten key Kratom alkaloids in Mitragyna speciosa leaf extracts and commercial products by ultra-performance liquid chromatography-tandem mass spectrometry.

Kratom (Mitragyna speciosa) is a psychoactive plant popular in the United States for the self-treatment of pain and opioid addiction. For standardization and quality control of raw and commercial kratom products, an ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method was developed and validated for the quantification of ten key alkaloids, namely: corynantheidine, corynoxine, corynoxine B, 7-hydroxymitragynine, isocorynantheidine, mitragynine, mitraphylline, paynantheine, speciociliatine, and speciogynine. Chromatographic separation of diastereomers, or alkaloids sharing same ion transitions, was achieved on an Acquity BEH C18 column with a gradient elution using a mobile phase containing acetonitrile and aqueous ammonium acetate buffer (10mM, pH 3.5). The developed method was linear over a concentration range of 1-200 ng/mL for each alkaloid. The total analysis time per sample was 22.5 minutes. The analytical method was validated for accuracy, precision, robustness, and stability. After successful validation, the method was applied for the quantification of kratom alkaloids in alkaloid-rich fractions, ethanolic extracts, lyophilized teas, and commercial products. Mitragynine (0.7%-38.7% w/w), paynantheine (0.3%-12.8% w/w), speciociliatine (0.4%-12.3% w/w), and speciogynine (0.1%-5.3% w/w) were the major alkaloids in the analyzed kratom products/extracts. Minor kratom alkaloids (corynantheidine, corynoxine, corynoxine B, 7-hydroxymitragynine, isocorynantheidine) were also quantified (0.01%-2.8% w/w) in the analyzed products; however mitraphylline was below the lower limit of quantification in all analyses.

Human cytomegalovirus latency and reactivation - a delicate balance between the virus and its host's immune system.

Human cytomegalovirus (HCMV) is a ubiquitous herpesvirus that still causes severe morbidity and mortality in immunocompromised individuals. During its evolution, the virus has developed sophisticated methods to evade immune recognition and to establish life-long persistence in its host. Today, we know that the virus establishes latency in myeloid lineage cells and that the virus is dependent on immune activation mechanisms to reactivate it from latency to produce a new viral progeny. During this process, a number of viral proteins are produced that interfere with different immune recognition pathways. The current knowledge of the delicate balance between the virus' continuous existence and its host's immune system will be summarized in this chapter.

The clinical assessment of a child's social and physical environment during health visits.

The quality of a child's home environment plays a critical role in long-term developmental status. The Pediatric Review and Observation of Children's Environmental Support and Stimulation (PROCESS) Inventory was developed to clinically assess aspects of the child's physical environment and the parent-child interaction during a health supervision visit. The final version was used with 76 mother-child pairs by two pediatricians. The Home Observation for Measurement of the Environment (HOME) Inventory was performed within 3 weeks on all pairs, and a laboratory observation of parent-child interaction was completed with 30 of the pairs. Correlations of the PROCESS with the HOME Inventory and parent-child interaction were 0.84 and 0.86 (less than 0.001), respectively. These significant correlations persisted while controlling for family income and education. When high and low scores of the HOME Inventory known to correlate with positive and negative developmental outcomes were cross-tabulated with PROCESS scores, low scores on the PROCESS identified 77% of low HOME Inventory scores and high scores on the PROCESS identified 95% of the high HOME Inventory scores. The PROCESS provides pediatricians a brief, easy-to-score, clinically useful, reliable, and valid method to measure children's home environments.

Management of children with failure to thrive in a rural ambulatory setting. Epidemiology and growth outcomes.

To evaluate the growth course of children with failure to thrive (FTT) who receive aggressive management, we reviewed the 2-year experience of a secondary level ambulatory diagnostic and management clinic for children with FTT in a mostly rural state. We examined the children managed in this setting for cause of FTT, for growth outcomes after 1 year according to FTT clinical type, and for differentiating predisposing sociodemographic information Of 154 children referred to this clinic, 131 were diagnosed as suffering from FTT. Eighteen were admitted to the hospital after initial outpatient evaluation, and 93 were followed for at least 1 year. Twenty-two (17%) suffered from organic, 59 (45%) non-organic, and 46 (35%) mixed etiology FTT. After 1 year, 48 (52%) of the FTT children were improved, 37 (40%) were stable, and 8 (9%) were worse. Children placed in foster care were more likely to be improved (78%). FTT children considered improved after 1 year demonstrated the following at the time of initial diagnosis: lower maternal income, lower maternal education, and lower family socioeconomic status; higher birth order; more often black; and less likely for the father to be present in the home (all p less than or equal to .05). This experience offers several insights into the growth course and team management of FTT children.