Imported malaria in Slovenia, 2001–2011

Background  

A retrospective analysis was conducted to determine the epidemiological and clinical characteristics of imported malaria in Slovenia.     

Embodied Deviance,Gender, and Epistemologies of Ignorance: Re-Visioning Drugs Use in a Neurochemical,Unjust World

The paper develops key notions needed for a feminist embodiment approach to drugs, their use and users. First, the term embodied deviance is defined in relationship to women drug users. Second, the bodily tasks of gendered drug use are defined to show how “normal” embodiment is foreclosed to women drug users. Third, disease regimes and epistemologies of ignorance are introduced. Fourth, another piece is inserted into the feminist embodiment puzzle –emotions. Simply, we look at some of the practices that emerge from the affective dimensions of gendered drug use. In the concluding section of my paper, I ask, “Where do we go from here?”     

Bioaccumulation and physiological effects of mercury in Pteris vittata and Nephrolepis exaltata

Anatomical, histochemical and biochemical approaches were used to study mercury uptake and phytotoxicity as well as anti-oxidative responses in two species of ferns [Chinese brake fern (Pteris vittata) and Boston fern (Nephrolepis exaltata)], grown in a hydroponic system. The roots of both cultivars accumulated large amounts of mercury, but exhibited limited mercury translocation to shoots. Mercury exposure led to more pronounced phytotoxicity accompanied by stronger oxidative stress in the shoots of P. vittata than in N. exaltata. N. exaltata established a more effective anti-oxidative system against mercury-induced oxidative stress than did P. vittata. The activity of anti-oxidative enzymes (superoxide dismutase, catalase and glutathione reductase) increased. The reduced ascorbate (ASA) and oxidized ascorbate (DHA) are regulated. Mercury exposure led to an increase in the concentration of glutathione (GSH) in both fern species. The present study suggests that N. exaltata is more tolerant to mercury exposure than P. vittata, which has been also reported to be more tolerant to arsenic exposure. N. exaltata may thus have potential for phytostabilization of soils or phytofiltration of waste water contaminated with mercury.     

Geostatistical analysis of biomarkers of genotoxicity in cattle, Bos taurus and Bos taurus × Bos indicus, sentinels near industrial facilities

This study, performed at the behest of ranchers living and working down-prevailing wind from industrial facilities located in Calhoun County, Texas investigated locational risks to ecosystem health associated with proximity to specific industrial complexes. Concerns expressed were for potential genotoxicity in cattle resulting from the release of complex chemical mixtures. The Comet Assay and flow cytometric evaluation of variations in DNA content were utilized to evaluate DNA damage. Bayesian geo-statistical analysis revealed the presence of important spatial processes. The Comet assay’s optical density provided a strong indication of increased damage down-prevailing wind from the industrial complexes. Results indicated that proximity to and location down-prevailing winds from industrial facilities increased the locational risk of genotoxicity in this sentinel species.

Smoking Trends and Educational Level in Italy in the Age Group 20–24, from 1950 to 2000

Smoking represents an important world research issue because of its diffusion among people and its effects on health. This study analyses, according to gender and educational level, the prevalence of smoking, in order to highlight the relationship between sociocultural status and smoking. Prevalence was calculated, with reference to Italian national data in 2000, by dividing a weighted population of 38,720,629 into 10 five-year birth cohorts. Results suggest that smoking is no longer perceived as being socially acceptable behavior. The prevalence declines for both sexes and educational levels, but in low educational levels the decline is slower. The study limitations are noted.     

Formulation and optimization of alkaline extracted ispaghula husk microparticles of isoniazid - in vitro and in vivo assessment

Microparticles containing isoniazid were prepared by the emulsification internal ionic gelation method using a novel, alkaline extracted ispaghula husk as a wall forming material. A four-factor three-level Box-Behnken design was employed to study the effect of independent variables on dependent variables. Sodium alginate concentration (X(1)), alkaline extraction of ispaghula husk (AEISP) concentration (X(2)), concentration of cross-linking agents (X(3)) and stirring speed (X(4)) were four independent variables considered in the preparation of microparticles, while the particle size (Y(1)) and entrapment efficiency (Y(2)) were dependent variables. Optimized microparticles exhibited 83.43% drug entrapment and 51.53?μm particle size with 97.80% and 96.37% validity, respectively, at the following conditions - sodium alginate (3.55% w/v), alkaline extracted ispaghula husk (3.60% w/v), cross-linker concentration (7.82% w/v) and stirring speed (1200?rpm). The optimized formulation showed controlled drug release for more than 12?h by following Higuchi kinetics via non-Fickian diffusion. The gamma scintigraphy of the optimized formulation in Wistar rats showed that microparticles could be observed in the intestinal lumen after 1?h and were detectable in the intestine up to 12?h, with decreased percentage of radioactivity (t(1/2) of (99m)Tc 4-5?h).     

Incidence of Healthcare-Associated Infections (HAIs) and the adherence to the HAIs’ prevention strategies in a military hospital in Alkharj

BackgroundHealthcare-associated infections (HAI) are considered one of the most common adverse events in health care service provision. In order to prevent the occurrence of HAIs, it is important to implement several prevention strategies.ObjectivesThis study aims to determine the incidence of healthcare-associated infections in a military hospital in Alkharj and the adherence to the HAIs’ prevention strategies.MethodsThis study included exporting data for all infected cases confirmed by the infection disease specialists in 2019. The data were collected from the reports that were written by infection control unit and infectious disease department.ResultsThe rate of healthcare associated infections (HAIs) in 2019 was 0.43% of total patient admissions. The rate of central line associated bloodstream infections in 2019 was 1.15 per 1000 central line days. The rate of catheter associated urinary tract infections in 2019 was 1.00 per 1000 catheter days. The rate of ventilator associated pneumonia in 2019 was 2.11 per 1000 ventilator days and the rate of surgical site infections in 2019 was 0.41 %.ConclusionThe rate of overall healthcare-associated infections (HAI) was low. The compliance rate of health care workers to preventive measures that control HAIs was generally high but there was a need for more awareness particularly regarding personal protective equipment and hand hygiene. So it is important to attend more awareness activities and workshops particularly regarding personal protective equipment and hand hygiene. Furthermore, infection control unit and infectious disease department in the hospital should support the robust HAI prevention programs.     

Aflatoxin,Fumonisin and Shiga Toxin-Producing Escherichia coli Infections in Calves and the Effectiveness of Celmanax?/Dairyman’s Choice? Applications to Eliminate Morbidity and Mortality Losses

Mycotoxin mixtures are associated with Shiga toxin-producing Escherichia coli (STEC) infections in mature cattle. STEC are considered commensal bacteria in mature cattle suggesting that mycotoxins provide a mechanism that converts this bacterium to an opportunistic pathogen. In this study, we assessed the mycotoxin content of hemorrhaged mucosa in dairy calves during natural disease outbreaks, compared the virulence genes of the STECs, evaluated the effect of the mucosal mycotoxins on STEC toxin expression and evaluated a Celmanax^®/Dairyman’s Choice™ application to alleviate disease. As for human infections, the OI-122 encoded nleB gene was common to STEC genotypes eliciting serious disease. Low levels of aflatoxin (1–3 ppb) and fumonisin (50–350 ppb) were detected in the hemorrhaged mucosa. Growth of the STECs with the mycotoxins altered the secreted protein concentration with a corresponding increase in cytotoxicity. Changes in intracellular calcium indicated that the mycotoxins increased enterotoxin and pore-forming toxin activity. A prebiotic/probiotic application eliminated the morbidity and mortality losses associated with the STEC infections. Our study demonstrates: the same STEC disease complex exists for immature and mature cattle; the significance of the OI-122 pathogenicity island to virulence; the significance of mycotoxins to STEC toxin activity; and, finally, provides further evidence that prebiotic/probiotic applications alleviate STEC shedding and mycotoxin/STEC interactions that lead to disease.     

Preparation of the albumin nanoparticle system loaded with both paclitaxel and sorafenib and its evaluation in vitro and in vivo

Paclitaxel and sorafenib loaded albumin nanoparticles (PTX-SRF-BSA-NPs) were prepared and studied here to avoid the toxicities from the excipients in the Taxol? and explore the effect of such combination on the antitumour efficacy and toxicity. PTX-BSA-NPs and so on were used as controls. The particle size, zeta potential, encapsulation efficiency and morphology were evaluated. Less than 70% of each drug released within 24?h. PTX and SRF existed as molecular or amorphous form in the PTX-SRF-BSA-NPs. The particle size did not change much after 2-month storage in freeze-dried form or 24?h in suspension. The treatment with PTX-SRF-BSA-NPs (7.5?mg?kg(-1) PTX?+?7.5?mg?kg(-1) SRF) exhibited lower myelosuppression than PTX-BSA-NPs (15?mg?kg(-1) PTX) while it remained or increased the antitumour effect in mice tumour models. Compared with the solution containing the same level of PTX and SRF, PTX-SRF-BSA-NPs demonstrated significantly lower haemolysis and myelosuppression effect.     

Novel in situ gelling ocular inserts for voriconazole-loaded niosomes: design,in vitro characterisation and in vivo evaluation of the ocular irritation and drug pharmacokinetics

This work aimed to develop voriconazole in situ gelling ocular inserts loaded with niosomal suspension. Niosomes and mixed niosomes were prepared using span 40 and span 60 with pluronic L64 and pluronic F127. The entrapment efficiency percentages (EE%), mean vesicle size, polydispersity index (PI), zeta potential and in vitro drug release of these niosomes were evaluated. F3-mixed niosomes prepared with span 60 and pluronic L64 was selected, due to its highest EE; optimum vesicle size with smallest PdI and suitable release pattern of the drug (63% after 8?h). In situ ocular inserts were prepared using sodium carboxymethylcellulose (CMC Na) and sodium alginate (ALG) and characterised for surface morphology, surface pH, water uptake, mucoadhesion and in vitro release. ALG in situ ocular insert (S₂) was selected for further in vivo evaluation of the ocular irritation and drug pharmacokinetics in the aqueous humour of rabbit's eyes. S₂ in situ gelling ocular insert was non-irritant and showed significantly (p?<?0.01) higher C_max, delayed T_max and increased bioavailability.     

Proliferation,Metabolic Activity,and Adipogenic Differentiation of Human Preadipocytes Exposed to 2 Surfactants In Vitro

Fat grafting is a pivotal technique for tissue repair. Adipose stromal cells, including preadipocytes, play a major role in the regenerative effects attributed to fat grafting. But the benefits are impaired by the low survival of the graft due to mechanical stress during harvesting, hypoxia, and nutrient deprivation. Nonionic surfactant molecules demonstrated their efficacy in preventing and repairing mechanical damage on the cellular membrane, but it is poorly understood if and how they affect cellular viability, proliferation, and differentiation. We investigated the influence of 2 nonionic surfactants, Kolliphor^®P188 and Kolliphor^®EL, on cultured human preadipocytes. We analyzed their effects on metabolic activity, cell number, adipogenic differentiation, and secretion of growth factors. Kolliphor^®P188 increased metabolic activity, while it did not influence proliferation and differentiation as well as growth factors release. Kolliphor^®EL confirmed its cytotoxic effect at the highest concentrations applied. Contrariwise, treatment with lower concentrations significantly raised metabolic activity, induced adipogenesis, and increased insulin-like growth factor-1 and vascular endothelial growth factor secretion. The effect on differentiation was inhibited by blocking peroxisome proliferator-activated receptor gamma. Our results revealed important effects of surfactants on preadipocytes' survival, proliferation, death, and the interplay with their environment. Particularly Kolliphor^®EL provides modes of action, which could recommend it for novel treatment to improve fat graft viability.     

Improvement of nutritional components and in vitro antioxidative properties of soy-powder yogurts using Lactobacillus plantarum

This research was the first to demonstrate changes in nutritional compositions (isoflavone and CLA) from the 50% methanol extracts of soy-powder milk (SPM) and soy-powder yogurt (SPY) through fermentation using Lactobacillus plantarum S48 and P1201 strains. The radical scavenging activities and protective effects against oxidative stress in LLC-PK₁ cells were also investigated. The average physicochemical characteristics including acidity and viable cell number as well as β-glucosidase activity increased with 0.2 → 0.7%, 7.5 → 9.8 log cfu/mL, and 0.0 3 → 1.75 U/g in SPYs. Total average isoflavones were considerably reduced (3180.3 → 2018.3 μg/g) with the increase of aglycone contents (191.8 → 770.2 μg/g), especially, daidzein exhibited the most remarkable increase rate (98.6 → 460.9 μg/g; > 4.8 times) during fermentation. The CLA and total phenolics also increased with significant differences (ND → 1.6 mg/g; 2.4 → 3.6 mg/GAE/g) between SPM and SPY. Interestingly, the cis-9, trans-11 CLA showed approximately 90% in total content. Moreover, the scavenging capacities against three radicals markedly increased with about 30% in SPYs, as the following order: ABTS > hydroxyl > DPPH. The protective effects on oxidative stress (pyrogallol: O₂^-, SNP: NO, and SIN-1: ONOO^?) were also observed high cell viabilities (>10%) under LLC-PK₁ cellular system. Our results suggest that SPY may be utilized as a potent source regarding natural antioxidants and beneficial components for health food and medical uses.     

Forms of Smoking Among Children Ages 8 to 12 Years in Prague,Czech Republic

Smoking is rarely monitored in children younger than 12 years of age. In order to learn more about this demographic group, smoking behavior among 3,887 children ages 8 to 12 years was evaluated in Prague, Czech Republic. Among the children evaluated, 24.0% reported having ever smoked. The mean age of the first smoking experience was 8.2 years (SD = 1.7). Cigarettes were the most common form of smoking (16.5%), but children reported the use of other forms of smoking including water pipes (7.4%), cigars (3.9%), and marijuana (0.8%). These findings have important public health implications.     

The influence of antibodies to TNF-α and IL-1β on haemodynamic responses to the cytokines,and to lipopolysaccharide,in conscious rats

1. Male, Long Evans rats (350–450 g) were anaesthetized and had pulsed Doppler probes and intravascular catheters implanted to allow monitoring of regional (renal, mesenteric and hindquarters) haemodynamics in the conscious state. Our main objectives were to:- assess the effects of administering human recombinant tumour necrosis factor (TNF)-α and human recombinant interleukin-1 (IL-1)β, alone and together; determine the influence of pretreatment with a mixture of antibodies to TNF-α and IL-1β on responses to co-administration of the cytokines; ascertain if pretreatment with a mixture of the antibodies to TNF-α and IL-1β had any influence on the responses to lipopolysaccharide (LPS).
2. TNF-α (10, 100 and 250 μg kg⁻¹, in separate groups, n=3, 9 and 8, respectively) caused tachycardia (maximum Δ, +101±9 beats min⁻¹) and modest hypotension (maximum Δ, −10±2 mmHg), accompanied by variable changes in renal and mesenteric vascular conductance, but clear increases in hindquarters vascular conductance; only the latter were dose-related (maximum Δ, +6±6, +27±9, and +61±12% at 10, 100 and 250 μg kg⁻¹, respectively).
3. IL-1β (1, 10, and 100 μg kg⁻¹ in separate groups, n=8, 8 and 9, respectively) evoked changes similar to those of TNF-α (maximum Δ heart rate, +69±15 beats min⁻¹; maximum Δ mean blood pressure, −14±2 mmHg; maximum Δ hindquarters vascular conductance, +49±17%), but with no clear dose-dependency.
4. TNF-α (250 μg kg⁻¹) and IL-1β (10 μg kg⁻¹) together caused tachycardia (maximum Δ, +76±15 beats min⁻¹) and hypotension (maximum Δ, −24±2 mmHg) accompanied by increases in renal, mesenteric and hindquarters vascular conductances (+52±6%, +23±8%, and +52±11%, respectively). Thereafter, blood pressure recovered, in association with marked reductions in mesenteric and hindquarters vascular conductances (maximum Δ, −50±3% and −58±3%, respectively). Although bolus injection of LPS (3.5 mg kg⁻¹) caused an initial hypotension (maximum Δ, −27±11 mmHg) similar to that seen with co-administration of the cytokines, it did not cause mesenteric or hindquarters vasodilatation, and there was only a slow onset renal vasodilatation. The recovery in blood pressure following LPS was less than after the cytokines, and in the former condition there was no mesenteric vasoconstriction. By 24 h after co-administration of TNF-α and IL-1β or after bolus injection of LPS, the secondary reduction in blood pressure was similar (−16±2 and −13±3 mmHg, respectively), but in the former group the tachycardia (+117±14 beats min⁻¹) and increase in hindquarters vascular conductance (+99±21%) were greater than after bolus injection of LPS (+54±16 beats min⁻¹ and +43±9%, respectively).
5. Pretreatment with antibodies to TNF-α and IL-1β (300 mg kg⁻¹) blocked the initial hypotensive and mesenteric and hindquarters vasodilator responses to co-administration of the cytokines subsequently. However, tachycardia and renal vasodilatation were still apparent. Premixing antibodies and cytokines before administration prevented most of the effects of the latter, but tachycardia was still present at 24 h.
6. Pretreatment with antibodies to TNF-α and IL-1β before infusion of LPS (150 μg kg⁻¹ h⁻¹ for 24 h) did not affect the initial fall in blood pressure, but suppressed the hindquarters vasodilatation and caused a slight improvement in the recovery of blood pressure. However, pretreatment with the antibodies had no effect on the subsequent cardiovascular sequelae of LPS infusion.
7. The results indicate that although co-administration of TNF-α and IL-1β can evoke cardiovascular responses which, in some respects, mimic those of LPS, and although antibodies to the cytokines can suppress most of the cardiovascular effects of the cytokines, the antibodies have little influence on the haemodynamic responses to LPS, possibly because, during infusion of LPS, the sites of production and local action of endogenous cytokines, are not accessible to exogenous antibodies.

     

The Combination of GIS and Biphasic to Better Predict In Vivo Dissolution of BCS Class IIb Drugs,Ketoconazole and Raloxifene

The formulation developments and the in vivo assessment of Biopharmaceutical Classification System (BCS) class II drugs are challenging due to their low solubility and high permeability in the human gastrointestinal (GI) tract. Since the GI environment influences the drug dissolution of BCS class II drugs, the human GI characteristics should be incorporated into the in vitro dissolution system to predict bioperformance of BCS class II drugs. An absorptive compartment may be important in dissolution apparatus for BCS class II drugs, especially for bases (BCS IIb) because of high permeability, precipitation, and supersaturation. Thus, the in vitro dissolution system with an absorptive compartment may help predicting the in vivo phenomena of BCS class II drugs better than compendial dissolution apparatuses. In this study, an absorptive compartment (a biphasic device) was introduced to a gastrointestinal simulator. This addition was evaluated if this in vitro system could improve the prediction of in vivo dissolution for BCS class IIb drugs, ketoconazole and raloxifene, and subsequent absorption. The gastrointestinal simulator is a practical in vivo predictive tool and exhibited an improved in vivo prediction utilizing the biphasic format and thus a better tool for evaluating the bioperformance of BCS class IIb drugs than compendial apparatuses.     

Correlates of Skin and Soft Tissue Infections in Injection Drug Users in a Syringe-Exchange Program in Malmö, Sweden

Background: Injection drug users (IDUs) are at increased risk of various medical conditions, including bacterial skin and soft tissue infections (SSTIs). SSTIs, which are painful and can lead to life-threatening complications, are common but scarcely studied. Objectives: To investigate life time, past 12 month and past 30-day prevalence for SSTI related to injection drug use, in IDUs at Malmö syringe exchange program (Malmö SEP). To investigate factors associated with having ever had an SSTI. Methods: IDUs were recruited from Malmö SEP (N = 80). They participated in a survey with questions about demographics, drug use, and experience of SSTIs. Factors independently associated with self-reported SSTI ever were assessed using logistic regression analysis. Results: The lifetime reported prevalence of SSTI was 58%, past 12 months 30%, and past 30 days 14%. Factors independently associated with SSTI ever were age (adjusted odds ratio [AOR] = 1.09; 95% confidence interval [CI] = 1.01–1.18), female sex (AOR = 6.75; 95% CI = 1.40–32.47), having ever injected prescribed drugs (AOR = 52.15; 95% CI = 5.17–525.67), and having ever injected in the neck (AOR = 8.08; 95% CI = 1.16–56.08). Conclusions/Importance: SSTI is common among IDUs in Malmö. Women and those injecting in the neck or injecting prescribed drugs (crushed tablets/liquids), are more likely to have had an SSTI.     

In Vitro and In Vivo Correlation of Hepatic Fraction of Metabolism by P450 in Dogs

1-Aminobenzotriazole (ABT) has been widely used as a nonspecific mechanism-based inhibitor of cytochrome P450 (P450) enzymes. It is extensively used in preclinical studies to determine the relative contribution of oxidative metabolism mediated by P450 in vitro and in vivo. The aim of present study was to understand the translation of fraction metabolized by P450 in dog hepatocytes to in vivo using ABT, for canagliflozin, known to be cleared by P450-mediated oxidation and UDP-glucuronosyltransferases–mediated glucuronidation, and 3 drug discovery project compounds mainly cleared by hepatic metabolism. In a dog hepatocyte, intrinsic clearance assay with and without preincubation of ABT, 3 Lilly compounds exhibited a wide range of fraction metabolized by P450. Subsequent metabolite profiling in dog hepatocytes demonstrated a combination of metabolism by P450 and UDP-glucuronosyltransferases. In vivo, dogs were pretreated with 50 mg/kg ABT or vehicle at 2 h before intravenous administration of canagliflozin and Lilly compounds. The areas under the concentration-time curve (AUC) were compared for the ABT-pretreated and vehicle-pretreated groups. The measured AUC_ABT/AUC_veh ratios were correlated to fraction of metabolism by P450 in dog hepatocytes, suggesting that in vitro ABT inhibition in hepatocytes is useful to rank order compounds for in vivo fraction of metabolism assessment.