Youth and Drugs: Society's Mixed Messages

Abstract

Drug activity depends on both the fine as well as the gross structure of the molecule. In this work, the properties of the molecule that are dependent on its fine structure such as: dipole moment, ionization potential and energies of the HOMO and LUMO were calculated for the optimized geometry of some drugs using Ab initio method and the GAMESS program. At physiological pH, the amine part of the drug would be partially protonated, the calculations were carried out on both the charged and the free base forms. Attempts to correlate the calculated parameters to the hallucinogenic activity of the studied drugs showed that a number of correlations could be obtained. Mathematical relations between the activity and the structural parameters were derived for the studied drugs. It should be noted that the gross properties of the molecule (size, geometry and lipophilicity) are important factors in determining the drug activity.     

Age governs gender-dependent islet cell autoreactivity and predicts the clinical course in childhood IDDM

Most IDDM patients temporarily restore some of their beta-cell function following the initiation of insulin therapy. The aim of this study was to analyse the influence of age, gender, metabolic state at diagnosis and presence of autoantibodies (GAD65 antibodies and IC A) on the duration of the clinical partial remission. In total, 149 consecutively diagnosed IDDM children, 0–16 y old (70F, 79M, mean age 9. 5 y) were studied. Partial remission was arbitrarily defined as the period when the insulin dose was below 0. 5 U/BW 24h^-1 and HbA1c below 7. 5%, and occurred in 119/149 patients with a duration between 1 and 38 months. Cox's regression analysis showed that the factors significantly associated with the duration of remission were age, gender, interaction between age and gender, ICA and a high initial HbAlc, whereas GAD65Ab had no influence. Young boys had the shortest remission period, while adolescent boys had the longest, as compared to young and adolescent girls. The IC A-negative patients ( n = 42) had a longer remission period (median 9. 7 months) than the ICA-positive children ( n = 107; 5. 0 months; p = 0. 0001), regardless of GAD65Ab status. We speculate that the relative insulin resistance, which is more pronounced in pubertal girls than in boys, may be associated with a more rapid increase of exogenous insulin requirement. These findings are important when evaluating the effect of islet cell autoreactivity on the clinical course of IDDM in children.     

Baseline Susceptibility and Laboratory Selection of Resistance to Bt Cry1Ab Protein of Chinese Populations of Yellow Peach Moth,Conogethes punctiferalis (Guenée)

Yellow Peach Moth (YPM), Conogethes punctiferalis (Guenée), is one of the most destructive maize pests in the Huang-Huai-Hai summer maize region of China. Transgenic Bacillus thuringiensis (Bt) maize provides an effective means to control this insect pest in field trials. However, the establishment of Bt resistance to target pests is endangering the continued success of Bt crops. To use Bt maize against YPM, the baseline susceptibility of the local populations in the targeted areas needs to be verified. Diet-overlay bioassay results showed that all the fourteen YPM populations in China are highly susceptible to Cry1Ab. The LC₅₀ values ranged from 0.35 to 2.38 ng/cm² over the two years of the collection, and the difference between the most susceptible and most tolerant populations was sevenfold. The upper limit of the LC₉₉ estimates of six pooled populations produced >99% larval mortality for representative eight populations collected in 2020 and was designated as diagnostic concentrations for monitoring susceptibility in YPM populations in China. Hence, we evaluated the laboratory selection of resistance in YPM to Cry1Ab using the diet-overlay bioassay method. Although the resistant ratio was generally low, YPM potentially could evolve resistance to Cry1Ab. The potential developmentof resistance by target pests points out the necessity to implement resistance management strategies for delaying the establishment of pest resistance to Bt crops.     

SLC11A1 is expressed in the human placenta across multiple gestational ages

The human placenta functions as an innate immune barrier to prevent fetal infection. However, the molecular mechanisms accounting for placental resistance to pathogens are currently poorly understood. The solute carrier family 11 member 1 (SLC11A1) is a divalent cation transporter expressed primarily by macrophages and neutrophils that is essential for controlling infections by intracellular pathogens such as Salmonella, Leishmania and Mycobacteria. This report demonstrates that SLC11A1 is expressed in the syncytiotrophoblast of the human placenta at multiple gestational ages. These results suggest that SLC11A1 may play a role in blocking productive placental infections by certain intracellular pathogens.     

Contributions of B cells to lupus pathogenesis

Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by the production of autoantibodies. This review summarizes first the results obtained in the mouse that have revealed how B cell tolerance is breached in SLE. We then review the B cell subsets, in addition to the autoAb producing cells, which contribute to SLE pathogenesis, focusing on marginal zone B cells, B-1 cells and regulatory B cells. Finally, we review the interactions between B cells and other immune cells that have been implicated in SLE, such as dendritic cells, macrophages, neutrophils and T cells.     

Frequency of Anti-AChR ϵ Subunit-specific Antibodies in MG

A definite diagnosis of myasthenia gravis (MG) relies heavily on acetylcholine receptor (AChR) antibody testing. The relatively high number of antibody-negative patients therefore, causes frequent uncertainty in confirming the diagnosis. We evaluated the sensitivity and specificity of a new, commercially available AChR antibody test that uses an approximately equal mixture of AChR from TE671-? (adult type) and TE671-γ (fetal type) cells. This assay was used to re-examine 365 seronegative MG sera in which AChR antibody had not been detected by the standard assay that uses fetal type AChR. The new assay detected anti-AChR antibodies in 17 (15.5%) of 110 patients with ocular type and in 33 (12.9%) of 255 patients with generalized type MG. Anti-AChR ? subunit-specific antibodies were present in 13.7% of the patients in whom no AChR antibody had been detected by the standard assay, showing an increase from 79 to 82% in overall diagnostic sensitivity.     

Augmenting the immunogenicity of DNA vaccines: role of plasmid-encoded Flt-3 ligand, as a molecular adjuvant in genetic vaccination

In this study, we have taken advantage of the unique property of a potent dendritic cell (DC) growth factor, Flt-3 ligand (FL), which could act as a vaccine adjuvant. Accordingly, a single injection of plasmid DNA coding for soluble FL (FLex) was shown to induce large numbers of DCs in various tissue compartments and was critical for generating high frequencies of antigen-specific (HIV gp120 and LCMV NP) immune responses in mice. Interestingly, this enhanced level of immune response is strictly dependent on the co-delivery (i.m.) of the DNA vaccines and hFLex DNA to mice harboring large numbers of DCs. The high frequencies of antigen-specific CD8(+) T cells were largely associated with the expansion phase of DCs in vivo. However, DC expansion and immune enhancement have not reciprocally maintained a linear correlation, suggesting that other factors, cytokines/chemokines, which have the potential to modulate the microenvironment of DCs, could influence immunological outcome in this vaccination modality.     

呼吸机相关性肺炎中鲍曼不动杆菌耐药性的动态分析

目的 分析呼吸机相关性肺炎(VAP)病原菌鲍曼不动杆菌的分布特点及耐药性,以指导临床合理用药.方法 对明确行气管插管或气管切开机械通气＞48h的66例患者的气管内抽吸物(ETA)进行细菌定量培养及抗菌药物敏感性测定.结果 回顾性分析66例VAP患者ETA培养出病原菌152株,鲍曼不动杆菌55株(36.2%);鲍曼不动杆菌首选抗菌药物是头抱哌酮舒巴坦和亚胺培南;鲍曼不动杆菌对常见抗菌药物的耐药率呈上升趋势,并呈多药耐药;头孢哌酮舒巴坦耐药率最低为54.5%,对亚胺培南耐药率达74.5%,且呈上升趋势.结论 动态监测鲍曼不动杆菌的耐药性变化,有助于临床合理应用抗菌药物.