2-甲酰(乙酰)取代喹啉缩氨基硫脲的合成

缩氨基硫脲类化合物有抗肿瘤、抗病毒和抗菌等多种药理活性。Barret等首次报道了乙二醛二缩氨基硫脲(Ⅰ)的抗疟活性。Klayman等研究了缩     

Modulation of the cellular immune response during Plasmodium falciparum infections in sickle cell trait individuals.

Plasma and peripheral blood mononuclear cells (PBMC) were obtained from P. falciparum-infected individuals with and without the sickle cell trait at diagnosis and 7 days after treatment. HbAA and HbAS patients were compared for levels of plasma soluble IL-2 receptors (IL-2R) and the in vitro cellular reactivity to affinity-purified soluble P. falciparum antigens (SPAg), PPD and phytohaemagglutinin (PHA). At diagnosis, HbAS patients with clinical disease had lower plasma-soluble IL-2R levels and parasite counts than the corresponding HbAA patients, whereas HbAS and HbAA patients with asymptomatic infections had comparable soluble IL-2R levels and parasite counts. PBMC from HbAS patients had higher proliferation and IFN-gamma production in response to SPAg than PBMC from HbAA patients. The difference in the lymphoproliferative responses to SPAg between the two groups was evident in patients with asymptomatic infections. In all patients, the clinical severity, the soluble IL-2R levels and the parasite counts were directly related. The former two were inversely related to the proliferative responses to SPAg. After treatment, all the studied parameters were comparable in the two groups. The study indicates that during P. falciparum infection, HbAS compared with HbAA patients had lower in vivo cellular activation and higher in vitro cellular reactivity in response to soluble malaria antigens.     

How the Dissection Laboratory Facilitates Integration of Learning: Presence of Abdominal Aortic Aneurysm with a Large Intracardiac Thrombus: A Rare Cadaver Finding

There is a debate among medical education experts on the application of dissection or prosection for learning anatomy. However, the literature reveals that the majority of published articles are in favor of dissection. In this article, we present a case of an abdominal aortic aneurysm (AAA) with intracardiac thrombus in a cadaver on routine dissection. We will discuss possible explanations for such finding and provide some insight into how this finding can support the significance of the cadaver-based teaching of anatomy of the medical students. Initially, the abdomen was dissected and exposed to study the abdominal structures in an anatomy class and later the thoracic region was dissected and all the clinical abnormalities were examined and documented. Autopsy of the clot was obtained for histopathology analysis. The intracardiac thrombus was present in the right atrium characterized by its projection into the superior vena cava, inferior vena cava, and the right ventricle. The AAA was extensive and inferior to the renal arteries constricting the entire inferior vena cava. Moreover, associated findings included presence of numerous collaterals in the thoracic region near the superior vena cava; histological examination of the clot showed extensive population of leukocytes. There were enlarged mediastinal lymph nodes. Our cadaver showed an excellent model for integrating between clinical anatomy and pathology by triggering medical students to think of normal and abnormal structures: often called “thinking outside the box.” Such an effort might help them in developing their thought processes and future medical careers.     

Activated protein C decreases plasminogen activator-inhibitor activity in endothelial cell-conditioned medium

Confluent cultures of endothelial cells from human umbilical cord were used to study the effect of activated human protein C (APC) on the production of plasminogen activators, plasminogen activator-inhibitor, and factor VIII-related antigen. Addition of APC to the cells in a serum-free medium did not affect the production of tissue-type plasminogen activator (t-PA) or factor VIII-related antigen; under all measured conditions, no urokinase activity was found. However, less plasminogen activator-inhibitor activity accumulated in the conditioned medium in the presence of APC. This decrease was dose dependent and could be prevented by specific anti-protein C antibodies. No decrease was observed with the zymogen protein C or with diisopropylfluorophosphate-inactivated APC. APC also decreased the t-PA inhibitor activity in endothelial cell-conditioned medium in the absence of cells, which suggests that the effect of APC is at least partly due to a direct effect of APC on the plasminogen activator- inhibitor. High concentrations of thrombin-but not of factor Xa or IXa-- had a similar effect on the t-PA inhibitor activity. The effect of APC on the plasminogen activator-inhibitor provides a new mechanism by which APC may enhance fibrinolysis. The data suggest that activation of the coagulation system may lead to a secondary increase of the fibrinolytic activity by changing the balance between plasminogen activator(s) and its (their) fast-acting inhibitor.     

Prevalence and risk factors of hyperprolactinemia among patients with various psychiatric diagnoses and medications

Abstract

Objectives: Hyperprolactinemia is a common adverse event associated with psychotropic medications (mainly antipsychotics) used in the management of schizophrenia and bipolar disorders. The aim of this study was to estimate the prevalence of hyperprolactinemia in psychiatric patients and to evaluate its association with various psychiatric diagnoses and the use of various psychotropic medications.

Methods: A cross-sectional observational study was conducted between July 2012 and June 2014. Patients were recruited from a number of hospitals located in the five regions of Saudi Arabia. Hyperprolactinemia was defined as blood prolactin levels >25?ng/mL in females and >20?ng/mL in males, regardless of the presence of symptoms.

Results: A total of 997 patients (553 males and 444 females) were included in the current analysis. The average blood prolactin level was 32.6?±?44.1?ng/mL, with higher levels among females than males (42.9?±?61.3 versus 24.4?±?18.6, p?<?.001). The prevalence of hyperprolactinemia was 44.3%, with no significant gender difference (41.9% in females versus 46.3% in males, p?=?.164) but with huge variability according to individual antipsychotic and other psychotropic medications. In the multivariate analysis adjusted for demographic and clinical characteristics, hyperprolactinemia was independently and positively associated with using antipsychotic medications (OR?=?2.08, 1.26–3.42, p?=?.004). Additionally, previous hospitalisation, diabetes and hypothyroidism were positively associated, whereas having primary depressive disorders was negatively associated.

Conclusions: We report a high prevalence of hyperprolactinemia among a large sample of psychiatric patients in Saudi Arabia, which was linked to the use of antipsychotic medications. Routine measurement of blood prolactin levels for all patients maintained on antipsychotic agents is recommended, regardless of symptoms.     

Incidence and risk factors of bacterial infections in children following autologous hematopoietic stem cell transplantation: Single‐center experience from Jordan

Bacterial infection is a serious sequela following AHSCT; however, limited data are available regarding pediatric recipients, especially in developing countries. We retrospectively analyzed the incidence and risk factors of bacterial infections during the first 100 days after AHSCT in children at KHCC in Amman, Jordan between January, 2005 and September, 2013. A total of 65 patients were identified, with median age of four yr (1–17). Forty‐seven patients (72.3%) had solid tumors and 18 (27.7%) had lymphoma. Bacterial infections were documented in 33 patients (50%), with a total of 63 episodes. Gram‐negative infection (57.1%) was more prevalent than Gram‐positive infection (38%). The risk of bacterial infections was higher among patients less than five yr of age (p = 0.028) and those who developed hypogammaglobulinemia requiring IVIG replacement (p = 0.001). Patients with solid tumors developed more bacterial infections compared to patients with lymphoma (p = 0.0057). No deaths were attributed to bacterial infection. Bacterial infection rate is high among recipients of AHSCT in Jordan with Gram‐negative bacteria being the most common.     

Identification of Candida species in the clinical laboratory: a review of conventional,commercial, and molecular techniques

In healthy individuals, Candida species are considered commensal yeasts of the oral cavity. However, these microorganisms can also act as opportunist pathogens, particularly the so‐called non‐albicans Candida species that are increasingly recognized as important agents of human infection. Several surveys have documented increased rates of C. glabrata, C. tropicalis, C. guilliermondii, C. dubliniensis, C. parapsilosis, and C. krusei in local and systemic fungal infections. Some of these species are resistant to antifungal agents. Consequently, rapid and correct identification of species can play an important role in the management of candidiasis. Conventional methods for identification of Candida species are based on morphological and physiological attributes. However, accurate identification of all isolates from clinical samples is often complex and time‐consuming. Hence, several manual and automated rapid commercial systems for identifying these organisms have been developed, some of which may have significant sensitivity issues. To overcome these limitations, newer molecular typing techniques have been developed that allow accurate and rapid identification of Candida species. This study reviewed the current state of identification methods for yeasts, particularly Candida species.