Hasil untuk "Toxicology. Poisons"

Haonan Li, Elizabeth A. Holzhausen, Devendra Paudel et al.

Abstract This study investigates independent and joint effects of fine particulate matter (PM2.5) components on early childhood neurodevelopment and explores emission sources of key toxic components. We included 165 mother-infant dyads from Southern California. Annual average concentrations of 15 PM2.5 components, including carbonaceous components, secondary inorganic salts, and trace elements, were estimated for the birth year. Neurodevelopment across cognitive, language, motor, social-emotional, and adaptive behavior domains was assessed at age 2 using Bayley-III Scales. Mixture effects and key contributors were evaluated using weighted quantile sum (WQS) and Bayesian kernel machine regression (BKMR). Source inference was conducted through inter-component clustering and spatial analysis. Linear regression showed PM2.5, sulfate (SO4 2−), nitrate (NO3 −), ammonium (NH4 +), copper (Cu), nickel (Ni), lead (Pb), and vanadium (V) were inversely, while calcium (Ca) and zinc (Zn) were positively, associated with adaptive behavior scores (p < 0.05). WQS showed negative associations between the mixture and adaptive behavior (p = 0.02–0.06), with Ni, Cu, V, and SO₄²⁻ as key contributors. BKMR showed similar trends. Ni, V, and SO4 2− likely originate from heavy oil combustion, and Cu from brake wear. Findings suggest that PM2.5 components, particularly from traffic and marine fuel combustion, may adversely affect adaptive behavior in early childhood.

Valeria Bettinsoli, Gloria Melzi, Irene Marchese et al.

This review examines various classes of drugs, focusing on their therapeutic and adverse effects, particularly in relation to immunostimulation. We emphasize the potential of new approach methodologies (NAMs) to study both expected and unexpected immunostimulatory effects. By evaluating the modes of action of different immunostimulatory drugs, we aim to provide insights into effectively assessing unwanted immunostimulatory responses. The review begins by exploring drugs that stimulate the immune system—including immunostimulants, monoclonal antibodies, chemotherapeutics, and nucleic acid-based drugs—to outline NAMs that could be employed to evaluate immunostimulation.

Karem H. Alzoubi, Abeer M. Rababa’h, Omar F. Khabour et al.

Background: Nedaplatin has demonstrated remarkable efficacy in combating various malignancies. However, the administration of nedaplatin has been associated with the induction of DNA damage within normal cells. Cilostazol is a phosphodiesterase III inhibitor with an antioxidant mechanism that could protect cells from genotoxicity. We aimed to evaluate the genotoxic effect of nedaplatin on cultured human lymphocytes and the potential protective effect of cilostazol on chromosomal damage induced by nedaplatin. Methods: The proposed nedaplatin’s genotoxic effect was studied in vitro by evaluating the frequencies of sister chromatid exchanges (SCEs) in human cultured lymphocytes. Both the mitotic and proliferative indices (MI and PI, respectively) were used to assess the cytotoxic effects of nedaplatin. Results: Nedaplatin significantly increased the frequency of SCEs compared to control and cilostazol-treated cells. The chromosomal injury induced by nedaplatin was significantly reduced by pretreatment of cells with cilostazol (P < 0.0001). Treating with cilostazol alone also reduced the frequency of SCEs, MI, and PI compared to the control group. Nedaplatin induced significant decreases in the MI and PI compared to the control group. Pretreatment with cilostazol partially debilitated the nedaplatin-induced changes in MI but not PI. Conclusion: Cilostazol ameliorated the genotoxicity of nedaplatin in cultured human lymphocytes.

Yunyi Wang, Ke Xu, Xiao Gao et al.

Abstract Background Increasing attention is being paid to the environmental and health impacts of nanoplastics (NPs) pollution. Exposure to nanoplastics (NPs) with different charges and functional groups may have different adverse effects after ingestion by organisms, yet the potential ramifications on mammalian blood glucose levels, and the risk of diabetes remain unexplored. Results Mice were exposed to PS-NPs/COOH/NH2 at a dose of 5 mg/kg/day for nine weeks, either alone or in a T2DM model. The findings demonstrated that exposure to PS-NPs modified by different functional groups caused a notable rise in fasting blood glucose (FBG) levels, glucose intolerance, and insulin resistance in a mouse model of T2DM. Exposure to PS-NPs-NH2 alone can also lead the above effects to a certain degree. PS-NPs exposure could induce glycogen accumulation and hepatocellular edema, as well as injury to the pancreas. Comparing the effect of different functional groups or charges on T2DM, the PS-NPs-NH2 group exhibited the most significant FBG elevation, glycogen accumulation, and insulin resistance. The phosphorylation of AKT and FoxO1 was found to be inhibited by PS-NPs exposure. Treatment with SC79, the selective AKT activator was shown to effectively rescue this process and attenuate T2DM like lesions. Conclusions Exposure to PS-NPs with different functional groups (charges) induced T2DM-like lesions. Amino-modified PS-NPs cause more serious T2DM-like lesions than pristine PS-NPs or carboxyl functionalized PS-NPs. The underlying mechanisms involved the inhibition of P-AKT/P-FoxO1. This study highlights the potential risk of NPs pollution on T2DM, and provides a new perspective for evaluating the impact of plastics aging.

Abdullah Al Marzan, Shatila Shahi, Md Sakil Arman et al.

Type-2 diabetes mellitus (T2DM), the predominant form of diabetes in adults, is a co-morbid condition that exacerbates the severity of many other diseases, including cardiovascular disease, obesity, dyslipidemia, hypertension, and cancer. Among these, cancer is particularly concerning due to elevated mortality rates and a distinct lack of cost-effective therapeutic interventions. Identifying novel biomarkers for improved early cancer detection is imperative. Therefore, an integrated bioinformatics analysis was conducted to elucidate the co-morbid relationship between T2DM and five different types of cancer, namely bladder (BLCA), breast (BRCA), colon (CRC), liver (HCC), and prostate cancer (PRAD) and identification of novel biomarkers for early cancer detection in individuals with T2DM. A significant comorbid relationship was observed among T2DM, BLCA, and BRCA through gene expression and pathway enrichment analysis, while a moderate association was observed for between T2DM, and PRAD. Notably, we identified 18 significant hub proteins in the context of cancer and T2DM, along with 16 transcription factors and 5 miRNAs. Among these, the hub proteins ESR1, PIK3CA, GNAI1, ERBB2, NR3C1, SNCA, TGFBR2, as well as the micro RNAs hsa-mir-335–5p, hsa-mir-16–5p, and hsa-mir-93–5p hold promise for understanding the comorbidities of T2DM and cancers; and could serve as valuable disease biomarkers for clinical diagnosis and prognosis. This study, centred on bioinformatics analysis for biomarker identification in comorbidities, paves the way for future research encompassing wet lab experimentation and translational studies. These endeavours are poised to validate and facilitate the integration of these findings into the realm of personalized medicine.

Andrea Di Nisio, Marta Trevisan, Stefano Dall’Acqua et al.

Perfluoroalkyl substances (PFASs) are persistent pollutants, raising concerns for human health. Legacy PFAS perfluoro-octanoic acid (PFOA) accumulate in brains of people at high environmental exposure, especially in areas enriched with dopaminergic neurons (DN). In vitro exposure to 10 ng/mL PFOA for 24 h was also associated with an altered molecular and functional phenotype of DN differentiated from human induced pluripotent stem cells (hiPSCs). Acetic acid, 2,2-difluoro-2-((2,2,4,5-tetrafluoro-5(trifluoromethoxy)− 1,3-dioxolan-4-yl)oxy)-ammonium salt (1:1), known as C6O4, is a new generation PFAS proposed to have a safer profile. Here we investigated the effect of C6O4 exposure on the molecular phenotype of hiPSC-derived DN. Cells were exposed to C6O4 for 24 h, at the concentration of 10 ng/mL, at neuronal commitment (DP1), neuronal precursor (DP2) and the mature dopaminergic (DP3) phases of differentiation. Liquid-chromatography/mass-spectrometry showed negligible cell accumulation of C6O4 at each differentiation stage and by staining with Merocyanine-540 we observed unaltered cell membrane fluidity. Immunofluorescence showed that the expression of tyrosine hydroxylase (TH) and βIII-Tubulin was unaffected by the exposure to C6O4 at each differentiation phase (respectively: DP1, p = 0.332; DP2, p = 0.623; DP3, p = 0.816, with respect to control unexposed conditions). Exposure to C6O4 is presumed to have minor effects on cell molecular/functional phenotype of developing human DN cells, requiring confirm on in vivo models.

Manisha B. Sinha, Gopal Gupta, N.N. Kolhe et al.

Introduction: Common carotid artery is a gateway to the blood supply to the head and neck region, including the brain. Previous cadaveric and few radiological studies have shown variation in the level of division and varying patterns of branches of the common carotid artery. Aim: The aim of the study is to investigate the prevalence of the commonest level of division of CCA in vivo through the use of CT angiography and the distance of STA (superior thyroid artery) from the level of bifurcation. Material and method: A total of 88 angiograms evaluated for study purpose, both right & left-sided views of the neck of all the 44 patients, have been taken into consideration during three years. Patients with intraparenchymal bleed and stroke, who had undergone CT angiography of the head and neck region, were selected and evaluated for study. Result: In the present study, the most frequent site of bifurcation of CCA was found to be type-II, which was at the level above the greater cornua of the hyoid bone (43.18%), and the least common site was type-V, which was at the level below the superior border of thyroid cartilage (1.13%). Conclusion: Variation in the bifurcation level of CCA results in variation in the origin and other parameters of other vessels (especially STA in this case) originating from the carotid arterial trunk. It leads to the possibility of misleading information to the clinicians during surgical and radiological procedures.

Chun-Hong Yu, Shui-Qing Yang, Lei Li et al.

Abstract Background Hydroquinone (HQ) is a phenolic metabolite of benzene with a potential risk for hematological disorders and hematotoxicity in humans. In the present study, an integrative analysis of microRNA (miRNA) and mRNA expressions was performed to identify potential pathways and miRNA-mRNA network associated with benzene metabolite hydroquinone-induced hematotoxicity. Methods K562 cells were treated with 40 μM HQ for 72 h, mRNA and miRNA expression changes were examined using transcriptomic profiles and miRNA microarray, and then bioinformatics analysis was performed. Results Out of all the differentially expressed genes (DEGs) and differentially expressed miRNAs (DEMs) induced by HQ, 1482 DEGs and 10 DEMs were up-regulated, and 1594 DEGs and 42 DEMs were down-regulated. HQ-induced DEGs were involved in oxidative stress, apoptosis, DNA methylation, histone acetylation and cellular response to leukemia inhibitory factor GO terms, as well as metabolic, Wnt/β-catenin, NF-κB, and leukemia-related pathways. The regulatory network of mRNAs and miRNAs includes 23 miRNAs, 1108 target genes, and 2304 potential miRNAs-mRNAs pairs. MiR-1246 and miR-224 had the potential to be major regulators in HQ-exposed K562 cells based on the miRNAs-mRNAs network. Conclusions This study reinforces the use of in vitro model of HQ exposure and bioinformatic approaches to advance our knowledge on molecular mechanisms of benzene hematotoxicity at the RNA level.

Narges Tamadoni, Ali Asghar Asgharnejad Farid, Hassan Asadzadeh

INTRODUCTION ... [1]. It is the responsibility of the wives to cope with the physical and mental problems of the veteran, especially when the injury is high or the veteran is suffering from post-trauma stress disorder [2]. Therefore, the wives of veterans in terms of mental health can be considered an at-risk group in society [3]. ... [4-7]. The challenges of this group, especially psychosocial security as a component affecting the lives of these people, are problematic and one of the issues to be considered important [8]. ... [9, 10]. Based on the growing trend of various psychological and social disorders among women, the role of preventive and therapeutic psychological interventions is of particular importance. One of the approaches that has been noticed by psychologists in recent years is acceptance and commitment therapy [11]. Du et al. have shown that acceptance and commitment therapy in women reduces their negative feelings and, consequently, improves their level of psychosocial and emotional adjustment and security [13]. The results of Mahmoudi et al.'s study indicate a steady upward trend in the scores of the Hope and Belief in a Fair World Scale for patients with breast cancer, which indicates the effectiveness of acceptance and commitment therapy in increasing these variables [14]. Howells, Ivtzan, and Eiroa-Orosa have also reported in a study that acceptance and commitment therapy affects women's social desirability and improves their positive aspects of health [15]. Aslani and Azadeh have concluded in another study that acceptance and commitment therapy has an effect on social well-being and security and improves psychological security and well-being in women [16]. Shojaeian also reported in a study that commitment and acceptance therapy is effective on women's life expectancy and mental health. In fact, by using acceptance and commitment therapy the level of life expectancy and mental health of women improves [17, 18]. AIM(S) This study aimed to evaluate the effectiveness of acceptance and commitment therapy on the psychosocial security and mental health of veterans' wives. RESEARCH TYPE The present study is a quasi-experimental study using a pretest-posttest design with a control group. RESEARCH SOCIETY, PLACE &TIME The statistical population of this study was the wives of veterans admitted to Niayesh Hospital in Tehran, Iran in 2021 from which 30 women were selected by available sampling and were examined. SAMPLING METHOD & NUMBER The researcher called 64 people from the available samples by telephone and finally, 30 people were randomly divided into two groups of experimental (15 people) and control (15 people). Inclusion criteria included: physical and mental health of individuals and exclusion criteria, a complete dissatisfaction with participation in sessions, and absence of more than two training sessions. USED DEVICES & MATERIALS Mental health questionnaire (reliability 0.91) [19, 20] and psychosocial security questionnaire (reliability 0.89) [21] were used to collect data. In the mental health questionnaire, if a person gets a score of 6 and a total score of 22 or higher in each subscale, it indicates symptoms and a lower score indicates higher mental health [19]. METHODS After the training package of acceptance and commitment therapy was developed based on the experts’ opinions, its validation was performed and it was intensively implemented in a pilot group of five volunteers. After selecting the final groups of the study, the participants of the two groups participated in a briefing session. Then the pre-test was held for both experimental and control groups on the same day and they filled the questionnaires. Then, the training package for the experimental group for 8 sessions per week was implemented by the first author of the article, who was responsible for performing psychological therapies in Niayesh Hospital (Table 1). During the training period, the participants in the control group did not receive any training. After completing the training course and after two months, a follow-up was performed. ETHICAL PERMISSION The ethical permissions of the present study were fully observed; participants could leave the research at any time and all their confidential information was stored in the questionnaire without exploitation. STATISTICAL ANALYSIS In the inferential statistics section, the analysis of covariance using SPSS 25 software was used to analyze the research data. FINDING BY TEXT Demographic data of the statistical sample showed that the age range of veterans' wives was between 23 to 54 years and their mean age was 48.5±4.61 years. The level of education of 50% of the samples was under high school diploma, 20% high school diploma, 25% an associate degree, and 5% higher than a bachelor. The results of the Kolmogorov-Smirnov test showed that the data were normal. In the pre-test stage, the mean scores of mental health and psychosocial security in the control and experimental groups were almost equal, but the results in the post-test showed that the mean scores of psychosocial security in the experimental group were higher than the control group (Table 2). Based on the Leven test and lack of significance for mental health and security variables, the condition of equality of intergroup variances was observed and the groups were homogeneous (Table 3). The value of F of the interaction of independent and covariant variables in the psychosocial security variable was also 3.04, which was not significant and it can be said that the correlation between covariant and independent variables was observed (Table 4). Therefore, an analysis of covariance was used. According to the obtained figures, after adjusting the pre-test scores, there was a significant effect on the factor between the subjects (F=6.42; p=0.01) and the mean scores of the experimental group increased significantly (Table 5). Also, the value of F was the interaction of independent and covariant in the mental health variable 2.76, which was not significant and it can be said that the correlation between variable and independent was observed (Table 6). According to the results obtained after adjusting the pre-test scores, there was a significant effect on the factor between the subjects (F=4.75; p=0.03) and the mean scores of the experimental group decreased significantly (Table 7). MAIN COMPARISION TO THE SIMILAR STUDIES The results showed that acceptance and commitment therapy had an effect on the psychological security of veterans' wives and increased women's psychosocial security. This finding is consistent with the results of Junkin as well as Mohammadi, Borjali, and Sohrabi studies [11, 12]. In explaining the obtained results, it can be said that acceptance and commitment therapy allows people to change their relationships with internal experiences, reduce empirical avoidance and increase acceptance flexibility and increase action in valuable ways in the first stage. Emphasis is also placed on strengthening a non-judgmental and enthusiastic relationship with experiences. Lack of judgment and flexibility can help increase psychological security. ... [22]. Howells, Ivtzan, and Eiroa-Orosa have also reported in a study entitled "Acceptance and Commitment Therapy on Happiness in Women" that acceptance and commitment therapy has an effect on women's happiness and social well-being and improves their positive health aspects [15]. By explaining the findings, it can be said that in acceptance and commitment therapy, the main emphasis is on accepting reality, accepting responsibility and the present. Therefore, the counselor helps the clients to evaluate their behavior and see if this behavior is practical and useful for them or not, and to set a realistic plan for better behaviors. Therefore, to achieve their goals, they must be committed to that plan. In other words, the goal of acceptance and commitment therapy is to reduce empirical avoidance and increase psychological flexibility by accepting unavoidable and distressing unpleasant feelings such as anxiety, cultivating mindfulness, and defining personal values related to behavioral goals. ... [23]. Also, the results of the research of Hartley and Shojaeian [6, 17] are consistent with the present study. ... [24]. SUGGESTIONS It is suggested that responsible institutions provide conditions for free psychological interventions, including acceptance and commitment therapy, along with appropriate economic, educational, and cultural support, for these families so that women have a positive evaluation of their social status. It is suggested to the practitioners that in real treatment sessions, regardless of the theoretical perspective or the style of counseling and treatment adopted, a plan to increase acceptance as well as a life based on the value of clients be considered to optimize the treatment of this disorder. LIMITATIONS The generalization of results requires caution due to cultural, ethnic, and social differences. Another limitation of the present study was the use of self-report scales. Coincidence of conducting research with the corona virus (Covid-19) epidemic was another limitation that made it difficult to collect data. CONCLUSIONS Psychological security and mental health are among the variables related to the health of veterans' wives and they can predict it. CLINICAL & PRACTICAL TIPS IN POLICE MEDICINE According to the results of the present study on the effectiveness of acceptance and commitment therapies in increasing psychological security and mental health, such interventions can be used in counseling and treatment centers of police headquarters. It is also possible to hold similar classes for wives and their family members in these centers to increase their awareness and skills, using the results of studies conducted. ACKNOWLEDGMENTS This article is taken from a research paper. We would like to thank all the participants in the research and all who helped us in this research. CONFLICT OF INTEREST The authors hereby declare that there is no conflict of interest in the present study. FUNDING SOURCES The present study had no financial support.

Yuan Lu, Jie Pan, Xiaoqing Zhu et al.

Abstract Background Aidi Injection (ADI), a Chinese herbal preparation with anti-cancer activity, is used for the treatment of hepatocellular carcinoma (HCC). Several clinical studies have shown that co-administration of ADI with doxorubicin (DOX) is associated with reduced toxicity of chemotherapy, enhanced clinical efficacy and improved quality of life for patients. However, limited information is available about the herb-drug interactions between ADI and DOX. The study aimed to investigate the pharmacokinetic mechanism of herb-drug interactions between ADI and DOX in a rat model of HCC. Methods Experimental HCC was induced in rats by oral administration of diethylnitrosamine. The HCC rats were pretreated with ADI (10 mL/kg, intraperitoneal injection) for 14 consecutive days prior to administration of DOX (7 mg/kg, intravenous injection) to investigate pharmacokinetic interactions. Plasma concentrations of DOX and its major metabolite, doxorubicinol (DOXol), were determined using ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). Results Preadministration of ADI significantly altered the pharmacokinetics of DOX in HCC rats, leading to increased plasma concentrations of both DOX and DOXol. The area under the plasma drug concentration-time curve (AUCs) of DOX and DOXol in rats pretreated with ADI were 3.79-fold and 2.92-fold higher, respectively, than those in control rats that did not receive ADI. Conclusions Increased levels of DOX and DOXol were found in the plasma of HCC rats pretreated with ADI.

Senthil Senthil, Y. S. Bansal, Dilip Vaishnav et al.

Deep Venous Thrombosis (DVT) and Subsequent Pulmonary Thromboembolism (PTE) in high altitude climbers is a well-known concept. The acclimatization process at high altitude is itself a thrombogenic event. Accordingly, when a physically nonprepared individual with preexisting thrombogenic risk factors attempts trekking at high altitude, they may end up with fatal thromboembolic events. Here, we report a case of a low-lander with multiple thrombogenic risk factors who developed DVT and PTE when he went for a trekking trip in the Himalayas. The risk factors, autopsy findings, and possible mechanism of developing fatal pulmonary embolism, in this case, are discussed here.

Olha V. Rudnytska, Olena O. Khita, Dmytro O. Minchenko et al.

The unique properties of single-walled carbon nanotubes (SWCNTs) make them viable candidates for versatile implementation in the biomedical devices. They are able to cross the blood–brain barrier, enter cells and accumulate in cell nuclei. We studied the effect of these carbon nanoparticles on the expression of genes associated with endoplasmic reticulum stress and proliferation, cell viability and cancerogenesis as well as microRNAs in normal human astrocytes. We have shown that treatment of normal human astrocytes by small doses of SWCNTs (2 and 8 ng/ml of medium for 24 hrs) affect the expression of DNAJB9, IGFBP3, IGFBP6, CLU, ZNF395, KRT18, GJA1, HILPDA, and MEST mRNAs as well as several miRNAs, which have binding sites at 3′-UTR of these mRNAs. These changes in the expression profile of individual mRNAs introduced by SWCNTs are dissimilar in magnitude and direction and are the result of both transcriptional and posttranscriptional mechanisms of regulation. It is possible that these changes in gene expressions are mediated by the endoplasmic reticulum stress introduced by carbon nanotubes and reflect the disturbance of the genome stability. In conclusion, the low doses of SWCNTs disrupt the functional integrity of the genome and possibly exhibit a genotoxic effect.

Chengke Wang, Hanli Yang, Jiangyu Li

The combination of microwave irradiation, ultrasonication treatment, and enzyme-assisted extraction approach was applied to study the extraction efficiency and antioxidative activity of curcumin from turmeric (Curcuma longa L.) using Response Surface Optimization (RSM). The effects of the power and treatment time of microwave irradiation and ultrasonication treatment, the types of enzymes, the amounts, and interaction time of pectinase on the extraction efficiency were studied. RSM was used to select the optimum extraction conditions by implementing Box–Behnken design. The extraction ratio and antioxidant activity of extracted species are 2.89% and 83.95% under the optimal conditions, respectively, which are close to the predicted values, and are much higher than the single extraction approach. Our results show that a versatile approach for biological compounds extraction from agricultural and natural products was successfully developed, and the bioactivity of extracted species could be kept well by using our proposed combination extraction methods.

L. M. Haddad, M. Shannon, J. Winchester

R. Cairns, A. Schaffer, N. Ryan et al.

BACKGROUND AND AIMS Pregabalin is a gamma-aminobutyric acid (GABA) analogue, used to treat neuropathic pain and epilepsy. Pregabalin was registered in Australia in 2005, and subsidized publically in 2013. We aimed to describe Australian patterns of pregabalin use and intentional poisoning, and identify people potentially at high risk of misuse. DESIGN AND SETTING Population-based retrospective cohort study of dispensings in the 10% sample of Australian Pharmaceutical Benefits Scheme (July 2012-February 2017); intentional poisoning calls to New South Wales Poisons Information Centre (NSWPIC) (2004-2016); intentional poisonings in two Australian toxicology service databases; and poisoning fatalities in NSW coronial records (2005-2016). PARTICIPANTS A total of 122 572 people dispensed pregabalin, people with intentional pregabalin overdoses managed by NSWPIC and the toxicology services and pregabalin-associated deaths referred to the NSW coroner. MEASUREMENTS Trends in dispensing, poisoning, death; demographics and patient characteristics, proportion of users at high risk of misuse (latent class analysis, LCA) and characteristics of high-risk users. FINDINGS Pregabalin dispensing increased by 73 424 per year [95% confidence interval (CI) = 61726-85 121 P < 0.001] between 2013 and 2016. NSWPIC received 1158 reports of intentional pregabalin poisonings, with a 53.8% increase per year, 2005-2016 (95% CI = 44.0-64.2%, P < 0.001). We identified 88 pregabalin-associated deaths, 57.8% yearly increase (95% CI = 30.0-91.6%, P < 0.001). Patients overdosing on pregabalin commonly co-ingested opioids, benzodiazepines and illicit drugs, and had high rates of psychiatric and substance use comorbidities; 14.7% of pregabalin users were classed by the LCA as at high risk of misuse, and were more likely to be younger, male, co-prescribed benzodiazepines or opioids, have more individual prescribers and higher pregabalin strengths dispensed. CONCLUSIONS There has been a dramatic increase in pregabalin use, poisonings and deaths in Australia since it became subsidized publicly in 2013. One in seven Australians dispensed pregabalin appears to be at high risk of misuse.

Jamila K. Hassan, Leonard W.T. Fweja

The purpose of this descriptive cross-sectional survey study was to assess the hygiene and safety precautions implemented by street food vendors in the Urban district of Zanzibar. The study involved 265 food vendors with immobile food vending sites. An organized researcher-executed questionnaire developed based on World Health Organization essential requirement for the safety of street-vended foods was used in data collection and complemented with observation. Data on environmental hygiene of the surveyed vending sites indicated that &lt;50% of the sites had both washbasin and soap in place and only 50.2% and 42.6% vending sites had waste bin and/or refuse sites respectively. Adherence to safe food handling practices were reflected in adequate protection of food from flies and dust (40.8%), cold storage of food (28.3%), saving food hot or reheating before sale (35.1%), dishing out food with spoon/ladle (53%) and food covering (57.4%). Hygienic and sanitary practices among food vendors demonstrated the following levels of adherence: washing hands with soap after toilet use (always 33.2%, sometimes 46.8%), washing hands with soap prior to preparing food (always 63%, sometimes 34%), keeping clean fingernail (98.5%), protection of hair (33.6%) and use of apron (29%). The results indicate poor environmental sanitation and waste handling practices, moderate adherence to food handling practices, safety measures and hygiene. Based on the results it is suggested that food safety and hygiene training should be a prior condition for starting a food-vending venture and be complemented with regular monitoring.

M. Schwenk

Synthetic toxic chemicals (toxicants) and biological poisons (toxins) have been developed as chemical warfare agents in the last century. At the time of their initial consideration as chemical weapon, only restricted knowledge existed about their mechanisms of action. There exist two different types of acute toxic action: nonspecific cytotoxic mechanisms with multiple chemo-biological interactions versus specific mechanisms that tend to have just a single or a few target biomolecules. TRPV1- and TRPA-receptors are often involved as chemosensors that induce neurogenic inflammation. The present work briefly surveys classes and toxicologically relevant features of chemical warfare agents and describes mechanisms of toxic action.

B. E. Benson, K. Hoppu, W. Troutman et al.

A. Vahidnia, G. V. D. Voet, Fabien Wolff

Girish Parthan, Shobhit Bhansali, Anura V. Kurpad et al.

Abstract Background Dipeptidyl peptidase 4 (DPP4) inhibitors improve glycemic control by promoting GLP1-mediated glucose-dependent insulin secretion and suppression of glucagon. Sitagliptin and vildagliptin have been shown to improve insulin sensitivity in patients with type 2 diabetes mellitus (T2DM). However, these patients had uncontrolled blood glucose at inclusion; therefore, the improvement in insulin sensitivity observed in these studies could be attributed to the drug per se and/or reduction in glucotoxicity. This study examines the effect of linagliptin on insulin sensitivity and β-cell function in patients with well-controlled T2DM. Methods Thirty patients with T2DM of duration ≤5 years, and having HbA1c < 7.5% were randomized to receive linagliptin, voglibose or placebo (n = 10 each), and were followed up for 6 months. Insulin sensitivity was assessed by hyperinsulinemic-euglycemic clamp, and insulin secretory response was measured by basal (M0) and postprandial (M1) β-cell function, and area under curve (AUC) for C-peptide during mixed meal tolerance test. Results The median HbA1c of the study subjects at inclusion was 6.9% and there was no significant difference among the groups in terms of age, duration of diabetes, body mass index (BMI), HbA1c, insulin sensitivity, AUC of C-peptide and M0 and M1 at baseline. At the end of the study, there was a modest reduction in HbA1c (− 0.2%) in the linagliptin group, and a significant decrease (− 0.8%) in the voglibose group, as compared to placebo (p = 0.038). However, there were no significant differences in insulin sensitivity, M0 and M1 and AUC of C-peptide, within, or among the groups. Conclusion Linagliptin modestly improves glycemic profile in patients with well controlled T2DM; however, it may not have an effect on insulin sensitivity in these patients. Trial registration Retrospectively Registered in Clinicaltrials.gov (ID number, NCT02097342). Registered: March 27, 2014.