Trichinella spiralis: shaping the immune response

The co-evolution of a wide range of helminth parasites and vertebrates represented a constant pressure on the host's immune system and a selective force for shaping the immune response. Modulation of the immune system by parasites is accomplished partly by dendritic cells. When exposed to helminth parasites or their products, dendritic cells do not become classically mature and are potent inducers of Th2 and regulatory responses. Treating animals with helminths (eggs, larvae, extracts) causes dampening or in some cases prevention of allergic or autoimmune diseases. Trichinella spiralis (T. spiralis) possess a capacity to retune the immune cell repertoire, acting as a moderator of the host response not only to itself but also to third party antigens. In this review, we will focus on the ability of T. spiralis-stimulated dendritic cells to polarize the immune response toward Th2 and regulatory mode in vitro and in vivo and also on the capacity of this parasite to modulate autoimmune disease--such as experimental autoimmune encephalomyelitis.     

Neonatal respiratory morbidity in late-preterm births in pregnancies with and without gestational diabetes mellitus

Objective: To evaluate neonatal respiratory morbidity in infants born late-preterm to mothers with or without gestational diabetes mellitus (GDM).

Methods: Analysis of a population-based cohort of all live-born singletons, born at 34 0/7 to 36 6/7 weeks to mothers with and without GDM, focusing on transient tachypnea of the newborn (TTN) and respiratory distress syndrome (RDS).

Results: The study group comprised 363 (4.7%) singletons born to mothers with GDM and the controls were 7400 born to mothers without GDM. Mothers with GDM were older (31.4?±?5.1 versus 29.5?±?5.1 years, p?p?Conclusion: GDM, per se, is not a major contributor to RDS in late pre-term infants. Rather, the combination of prematurity and cesarean birth act independently to increase the risk of respiratory morbidity.     

Modeling the T cell immune response: a fascinating challenge

The immune system is designed to protect the organism from infection and to repair damaged tissue. An effective response requires recognition of the threat, the appropriate effector mechanism to clear the pathogen and a return to homeostasis with minimal damage to self-tissues. T cells play a central role in orchestrating the immune response at all stages of the response and have been the subject of intense study by both experimental immunologists and modelers. This review examines some of the more critical questions in T cell biology and describes the latest attempts to address those questions using approaches that combine mathematical modeling and experiments.     

Induction of CYP1A2 by heavy coffee consumption in Serbs and Swedes

Objectives To investigate the influence of coffee consumption on CYP1A2 enzyme activity controlling for the effects of smoking and oral contraceptive (OC) use among Serbs and Swedes and to compare CYP1A2 activity between the two populations. Methods Data on oral contraceptive use, habitual coffee consumption and smoking habits were obtained from 100 Serbian and 149 Swedish healthy volunteers using a detailed questionnaire. CYP1A2 activity was estimated by plasma paraxanthine/caffeine (17X/137X) ratio analysed by reversed-phase HPLC after oral administration of 100 mg caffeine. Results Daily consumption of at least three cups of coffee significantly increased CYP1A2 enzyme activity in both Serbs (P = 0.0002) and Swedes (P < 0.0001). Among non-smokers and non-OC users, heavy coffee consumption significantly increased CYP1A2 activity in Serbs (mean difference 0.11; 95% CI of the mean difference 0.04, 0.18; P = 0.003) and Swedes (mean difference 0.07; 95% CI of the mean difference 0.01, 0.12; P = 0.02). Significantly higher 17X/137X ratio was detected in Serbian smokers compared to non-smokers. There was no significant gender difference in CYP1A2 activity in Serbs. Controlling for the effect of smoking, heavy coffee consumption habit and oral contraceptive use, significantly lower 17X/137X ratio was observed in Serbs than in Swedes (P = 0.0003). Conclusions Habitual heavy coffee consumption increases CYP1A2 activity. Polycyclic aromatic hydrocarbons formed during roasting of coffee beans might partly be responsible for this effect. The reason for the observed lower CYP1A2 activity in Serbs as compared to Swedes remains to be investigated.     

Adulteration of low-delta-9-tetrahydrocannabinol products with synthetic cannabinoids: Results from drug checking services

Since late 2019, low-delta-9-tetrahydrocannabinol (THC) preparations adulterated with synthetic cannabinoids (SCs) have been frequently observed in Switzerland. The unawareness of users concerning the presence of SCs and the typically higher potency and toxicity of SCs, when compared with THC, can result in increased health risks. In Switzerland, low-THC (<1%) cannabis products, except hashish, are legal. These products can act as carrier materials for SCs. In this study, cannabis samples and user self-reports received through three drug checking services were collected and analysed, to gain deeper insight into this new phenomenon. Samples were collected from January 2020 to July 2021. Liquid chromatography coupled with high-resolution mass spectrometry was used for the qualitative screening and semi-quantification of SCs, while gas chromatography with flame ionization detector was applied for the quantification of THC and cannabidiol levels. Reported adverse effects were compared between users who consumed adulterated (SC-group) and non-adulterated (THC-group) products. Of a total 94 samples, 50% contained up to three different SCs. MDMB-4en-PINACA was most often detected. All adulterated cannabis flowers contained ≤1% THC. Adulterated hashish also typically presented low THC-levels (median: 0.8%). The SC-group was associated with higher numbers of adverse events (p = 0.041). Furthermore, psychologic (p = 0.0007) and cardiologic (p = 0.020) adverse effects were more profound in the SC-group than in the THC-group. Drug checking services enabled the timely detection and monitoring of new and potentially dangerous trends. Furthermore, due to user-reports, additional valuable information was gained on adverse events associated with the consumption of novel SCs.     

Lung Function in Gypsies in Greece

The relationship between lung function and smoking and dietary habits was examined in 121 Gypsies (62 males, 59 females) who were 14-70 y of age and who lived in Greece. All were examined clinically, after which they all participated in spirometry tests. Half of the study group had abnormal (< 80% of predicted) forced vital capacity, 36.4% had abnormal (< 80% of predicted) forced expiratory volume in 1 sec, and 5% had serious lung function disturbances (forced vital capacity < 50% of predicted). Approximately 70% of subjects were smokers, and their diets were rich in alcohol and meat; they ate very few salads and oranges. Consequently, decreased lung function might be a major health problem in Gypsies in Greece. Organization of preventive health strategies should improve the overall health of this study group.     

Mixed steroidal 1,2,4,5-tetraoxanes: antimalarial and antimycobacterial activity

Mixed 1,2,4,5-tetraoxanes possessing simple spirocycloalkane and spirocholic acid-derived substituents were prepared and shown to have significantly higher in vitro antimalarial activity than bis-substituted tetraoxanes. Out of 41 synthesized tetraoxanes, 12 were in vitro more potent against Plasmodium falciparum chloroquine-resistant W2 clone than artemisinin, and the most potent one was 2.4 times as active as arteether. In addition, 9 compounds exhibit higher activity than chloroquine against P. falciparum chloroquine-susceptible D6 clone. Cytotoxicity was assessed for most active compounds against the Vero cell line, showing a cytotoxicity/antimalarial potency ratio of 1/(1400-9500). For the first time, tetraoxanes were screened against Mycobacterium tuberculosis with MICs as low as 4.73 microM against H37Rv strain. Mixed tetraoxanes were synthesized in a simple procedure from cholic acid methyl esters by direct coupling of steroidal gem-dihydroperoxide to simple ketones and further transformed into corresponding acids and amides.     

Liposomal delivery system enhances anti-inflammatory properties of curcumin

Curcumin is a well-established natural antioxidant and anti-inflammatory agent. Up till now its potential in treatment of vaginal inflammation has not been evaluated. We are aiming at developing liposomal delivery system for curcumin targeting vaginal administration. Liposomes as nanosized phospholipid-based vesicles are expected to solubilize curcumin and enhance its activity, thus serving as an advanced topical formulation in the treatment of vaginal inflammation. Curcumin and curcuminoids were analyzed by the high-performance liquid chromatography method. Liposomes containing curcumin/curcuminoids of various sizes were prepared and characterized. Antioxidant activities of curcumin and liposomal curcumin were compared based on 1,1-diphenyl-2-picrylhydrazyl radical scavenging and superoxide dismutase activities. The anti-inflammatory activities were determined by measuring the inhibition of lipopolysaccharide -induced nitric oxide, interleukin-1β, and tumor necrosis factor-α production in macrophage RAW 264.7 cells. Curcumin/curcuminoids were encapsulated in phosphatidylcholine vesicles with high yields. Vesicles in the size range around 200 nm were selected for stability and cell experiments. Liposomal curcumin were found to be twofold to sixfold more potent than corresponding curcuminoids. Moreover, the mixture of curcuminoids was found to be more potent than pure curcumin in regard to the antioxidant and anti-inflammatory activities. Liposomal delivery systems for curcumin are promising formulations for the treatment of vaginal inflammation.     

Supercritical fluid drying of carbohydrates: selection of suitable excipients and process conditions.

The processibility of 15 carbohydrates, more or less commonly used, was investigated as excipients in supercritical fluid drying. The focus was on the ability to produce amorphous powder, the stability of the powders towards crystallisation, and the residual water and ethanol content. The aqueous solutions were sprayed into a pressurised carbon dioxide-ethanol mixture flowing cocurrently through a coaxial two-fluid nozzle. The powder characteristics appeared to be influenced by the supersaturation level reached during the SCF-drying process and by the properties of the sugar species, such as water solubility and glass transition temperature, or the solution viscosities. The stability and the residual solvent content of a selected set of sugars and some mixtures were further analysed. The stability of amorphous powders was investigated at 4 degrees C, room temperature, 40 and 50 degrees C. Lactose, maltose, trehalose, raffinose, cyclodextrin, low-molecular-weight dextran and inulin could form free-flowing powders that remained amorphous during the 3-month stability study. Sucrose had to be mixed with other sugars to form a stable amorphous powder. Ethanol could be entrapped in supercritical fluid dried low-molecular-weight sugars, whereas polysaccharide powders were free of ethanol. Measures to prevent or overcome the presence of ethanol are discussed.