Brain-specific chemical delivery systems for beta-lactam antibiotics. Synthesis and properties of some dihydropyridine and dihydroiosquinoline derivatives of benzylpenicillin

Six chemical delivery systems (CDS) were synthesized for benzylpenicillin in order to improve its transport across the blood-brain barrier. The CDS's were based on a dihydropyridine----quaternary pyridinium ion redox system, analogous to the naturally occurring NADH----NAD+ system. Two different types of CDS's were prepared: benzylpenicillin esters of diols in which the other hydroxyl group is esterified by dihydrotrigonelline and benzylpenicillin esters of amino alcohols in which the amine group is acylated by dihydrotrigonelline, or by 1,2-dihydro-2-methyl-4-isoquinolinecarboxylic acid. Lipophilicities of the CDS's were proved to be much higher than those of benzylpenicillin by using Rm values as lipophilicity indexes. Upon oxidation, all of the CDS's gave the quaternary ion forms. Kinetic studies in buffer (pH profiles) indicated that the quaternary salts released benzylpenicillin in pH range of 5-9 via hydrolysis. The CDS's in acidic media yielded as the major reaction product 6-hydroxy-1,4,5,6-tetrahydropyridines as a result of water addition, while in basic conditions benzylpenicillin was released. The water addition reaction was dependent on the CDS's structure, being more prevalent in the case of the "amide-esters". The dihydroisoquinoline CDS was rather stable in the pH range 5-8.     

Reliability and factorial structure of the Chinese version of the General Health Questionnaire

The Chinese version of the General Health Questionnaire (GHQ) was administered to 2,150 Chinese secondary school students. The GHQ was found to have high internal consistency as a scale and high item-total correlations for most of the items. Factor analysis with a five-factor solution showed that five factors were abstracted from the scale, namely, anxiety, depression, inadequate coping, interpersonal dysfunctioning, and sleep disturbances. By randomly splitting the total sample into two subsamples, these five factors could be reproduced reliably, and high coefficients of congruence were found. The psychometric properties of the Chinese version of the GHQ and the implications of the findings were discussed.     

Natural and immune cytolysis of canine distemper virus-infected target cells.

Natural and immune cytolysis of canine distemper virus (CDV)-infected target cells in vitro is described. Lymphocytes expressing natural cytotoxicity were found in specific-pathogen-free beagle dogs and in beagle-coonhound crosses before vaccination with CDV and indefinitely after vaccination, when the ephemeral immune lymphocyte-mediated cytotoxicity (ILMC) had declined. In contrast to the natural lymphocyte-mediated cytotoxicity, the ILMC was genetically restricted, could not be blocked by CDV-specific antibody, and was effective against measles virus-infected as well as CDV-infectd target cells. Lymphocyte populations were depleted of Fc receptor and surface immunoglobulin-bearing cells by rosetting techniques and tested in comparison. An antibody-dependent cell-mediated cytotoxicity was demostrated against CDV-infected target cells that were preincubated with CDV antibody when Fc receptor-bearing lymphocytes were not removed. The ILMC was measurable for approximately 10 days beginning at 6 days post-vaccination. In contrast, CDV antibody measured by virus neutralization and humoral cytotoxicity was detectable by 6 days postvaccination and persisted at peak levels for at least 5 months.     

The Impact of Positive Youth Development Attributes on Posttraumatic Stress Disorder Symptoms Among Chinese Adolescents Under COVID-19

PurposeThis study examined the prevalence of posttraumatic stress disorder (PTSD) symptoms among adolescents in mainland China under COVID-19. The direct effects of the perceived threat of COVID-19 and positive youth development (PYD) qualities, as well as the moderating effect of PYD qualities on PTSD symptoms, were studied.MethodsFive schools in Chengdu, Sichuan, China, participated in this study. Two waves of data were collected before school lockdown (Wave 1, between December 2019 and January 2020) and after school resumption (Wave 2, between June 2020 and July 2020), respectively. A total of 4,981 adolescents aged above 11 years (Mean age = 13.15, SD = 1.32 at Wave 1, 51.5% girls) completed questionnaires at both waves. Students responded to measures of PYD qualities at both waves and perceived threat and PTSD symptoms at Wave 2.ResultsA total of 517 adolescents (10.4%) could be regarded as having PTSD. Results indicated significant unique main effects of perceived threat (β = .13, p < .001) and Wave 1 PYD qualities (β = ?.16, p < .001) on PTSD symptoms. Besides, results showed a significant moderating effect of PYD qualities in mitigating the negative impact of perceived threat on PTSD symptoms.ConclusionsThis study revealed the protective effect of PYD attributes in reducing the negative influence of traumatic situations such as COVID-19 on adolescent mental health. Results underscore the importance of promoting PYD qualities in adolescents in mainland China via effective PYD programs.     

Osteochondroma and secondary synovial osteochondromatosis

Secondary synovial osteochondromatosis (SOC) is a rare disorder caused by a variety of joint disorders. Two unusual cases of secondary SOC are presented. The first patient is a 43-year-old man with extensive SOC developing within a bursa surrounding an osteochondroma of the pubic bone. The second patient is a 23-year-old man who developed florid and progressive SOC of his hip joint following excision of a femoral neck osteochondroma. SOC recurred despite three excisions over a 15-month period. Imaging was useful in pre-operative diagnosis of bursal SOC in the first patient and in detecting multiple recurrences in the second patient. Both cases illustrate prominent SOC developing secondary to osteochondroma. The different hypotheses regarding bursal and secondary SOC are reviewed. Received: 8 October 1998 Revision requested: 28 October 1998 Revision received: 13 November 1998 Accepted: 16 November 1998     

Haemoptysis in healthy children due to unsuspected foreign body

Abstract: Haemoptysis in otherwise healthy children is an uncommon event. Two cases of massive haemoptysis, subsequently requiring lobectomy, are discussed. In each case, foreign vegetable matter was identified despite previously normal bronchoscopy and minimal changes on chest radiograph.     

Zinc replenishment reduces esophageal cell proliferation and N- nitrosomethylbenzylamine (NMBA)-induced esophageal tumor incidence in zinc-deficient rats

Previous work has shown that sustained increased and decreased cell proliferation, induced by dietary zinc deficiency and caloric restriction respectively, influence the course of N- nitrosomethylbenzylamine (NMBA)-induced esophageal carcinogenesis in rats. The present study considered whether the increased cell proliferation and esophageal tumor incidence induced by zinc deficiency are reversed upon zinc replenishment. Weanling rats were maintained initially on a deficient diet containing 4 p.p.m. zinc. After 5 weeks, carcinogen-treated animals were given six intragastric doses of NMBA (2 mg/kg twice weekly). Controls were untreated. After the second NMBA dose, the rats were divided into three dietary groups. One group was continued on the deficient diet, while the other two groups were switched to diets containing either 75 or 200 p.p.m. zinc, with half of the members in each group fed ad libitum and half pair-fed with deficient rats. NMBA-untreated controls were similarly replenished. At various time points, esophageal cell proliferation was assessed in five animals from each group by immunohistochemical detection of cells in S phase, with in vivo 5-bromo-2'deoxyuridine labeling. At 11 weeks after the first dose, esophageal tumor incidence was greatly reduced, from 100% in the deficient group to 26 and 14% respectively in the replenished groups fed ad libitum 75 and 200 p.p.m. zinc and to 14 and 11% respectively in the replenished groups pair-fed 75 and 200 p.p.m. zinc. In addition, the number of tumors per esophagus was reduced from 9.93 +/- 4.25 in deficient rats, to a range of 0.11 +/- 0.31-0.30 +/- 0.54 in replenished animals. Following zinc replenishment, esophageal cell proliferation, as measured by labeling index (LI), the number of labeled cells and the total number of cells, was markedly decreased in NMBA-untreated and -treated esophagi as compared with those in corresponding deficient esophagi. Thus, the esophageal cell proliferation induced by zinc deficiency is reversed by zinc replenishment and replenished animals have a markedly lower incidence of esophageal tumors.