Identifying the sociodemographic determinants of subjective health complaints in a cross-sectional study of Greek adolescents

Background

Experience of common health symptoms without a clear physical or psychological cause, such as headache or dizziness, is often reported in adolescence. The present study attempted to investigate associations of self-reported subjective health complaints (SHC) with a number of sociodemographic factors of Greek adolescents.

Methods

Questionnaires were administered to a Greek nationwide random school-based sample of adolescents aged 12 to 18 years and their parents in 2003. Data from 922 adolescent-parent pairs were analyzed (response rate?=?63%). Adolescents?? reported subjective health complaints were assessed for their association with a number of sociodemographic factors: age, sex, type of area of residence according to level of urbanization, immigration background, parental education and employment status, family socioeconomic status and perceived quality of financial resources (PQFR). Multiple linear regression analysis was used to assess the association of the aforementioned factors with subjective health complaints as the dependent variable.

Results

Most sociodemographic variables, apart from area of residence and immigration background, were independently associated with subjective health complaints in the univariate analyses. The multiple linear regression analysis, however, limited the factors that could predict adolescents?? subjective health complaints to four (age, sex, Family Affluence Scale score and perceived quality of financial resources). Some considerations regarding parental employment status and immigration background are highlighted.

Conclusions

Our study highlights the sociodemographic components of subjective health complaints in the Greek adolescent population. The need to include adolescent-specific measures when collecting information on adolescents?? social background is underlined. Identifying vulnerable adolescent populations could lead to effective health promoting and preventive interventions.     

High‐frequency p16INK4A promoter methylation is associated with histone methyltransferase SETDB1 expression in sporadic cutaneous melanoma

Epigenetic mechanisms participate in melanoma development and progression. The effect of histone modifications and their catalysing enzymes over euchromatic promoter DNA methylation in melanoma remains unclear. This study investigated the potential association of p16^INK4A promoter methylation with histone methyltransferase SETDB1 expression in Greek patients with sporadic melanoma and their correlation with clinicopathological characteristics. Promoter methylation was detected by methylation‐specific PCR in 100 peripheral blood samples and 58 melanoma tissues from the same patients. Cell proliferation (Ki‐67 index), p16^INK4A and SETDB1 expression were evaluated by immunohistochemistry. High‐frequency promoter methylation (25.86%) was observed in tissue samples and correlated with increased cell proliferation (P = 0.0514). p16^INK4A promoter methylation was higher in vertical growth‐phase (60%) melanomas than in radial (40%, P = 0.063) and those displaying epidermal involvement (P = 0.046). Importantly, p16^INK4A methylation correlated with increased melanoma thickness according to Breslow index (P = 0.0495) and marginally with increased Clark level (I/II vs III/IV/V, P = 0.070). Low (1–30%) p16^INK4A expression was detected at the majority (19 of 54) of melanoma cases (35.19%), being marginally correlated with tumor lymphocytic infiltration (P = 0.078). SETDB1 nuclear immunoreactivity was observed in 47 of 57 (82.46%) cases, whereas 27 of 57 (47.37%) showed cytoplasmic immunoexpression. Cytoplasmic SETDB1 expression correlated with higher frequency of p16^INK4A methylation and p16^INK4A expression (P = 0.033, P = 0.011, respectively). Increased nuclear SETDB1 levels were associated with higher mitotic count (0–5/mm² vs >5/mm², P = 0.0869), advanced Clark level (III‐V, P = 0.0380), epidermal involvement (P = 0.0331) and the non‐chronic sun exposure‐associated melanoma type (P = 0.0664). Our data demonstrate for the first time the association of histone methyltransferase SETDB1 with frequent methylation of the euchromatic p16^INK4A promoter and several prognostic parameters in melanomas.     

Regulation of faecal biomarkers in inflammatory bowel disease patients treated with oral mastiha (Pistacia lentiscus) supplement: A double‐blind and placebo‐controlled randomised trial

There is a keen research upon the effects of nutraceuticals on inflammatory bowel disease. The purpose of this study was to explore the effect of mastiha supplement, rich in bioactive nutraceuticals, in active inflammatory bowel disease. This is a randomised, double‐blind, placebo‐controlled clinical trial. Α total of 60 inflammatory bowel disease patients were enrolled and randomly allocated to mastiha (2.8 g/day) or placebo groups for 3 months adjunct to stable medical treatment. Medical and dietary history, Inflammatory Bowel Disease Questionnaire (IBDQ), Harvey‐Bradshaw index, partial Mayo score, biochemical indices, faecal, and blood inflammatory markers were assessed. A clinically important difference between groups in IBDQ was defined as primary outcome. Inflammatory Bowel Disease Questionnaire score significantly improved in verum compared with baseline (p = 0.004). There was a significant decrease in faecal lysozyme in mastiha patients (p = 0.018) with the mean change being significant (p = 0.021), and significant increases of faecal lactoferrin (p = 0.001) and calprotectin (p = 0.029) in the placebo group. Fibrinogen reduced significantly (p = 0.006) with a significant mean change (p = 0.018), whereas iron increased (p = 0.032) in mastiha arm. Our results show regulation of faecal lysozyme by mastiha supplement adjunctive to pharmacological treatments in active inflammatory bowel disease. An effect secondary to a prebiotic potency is proposed.     

Development and validation of an EI-GC-MS method for the determination of methadone and its major metabolites (EDDP and EMDP) in human breast milk

Methadone is used extensively for the maintenance of opioid-addicted pregnant women. Because methadone and the two major metabolites, 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine (EDDP) and 2-ethyl-5-methyl-3,3-diphenylpyrroline (EMDP), are excreted into breast milk, a sensitive and specific gas chromatographic-mass spectrometric method has been developed, optimized, and validated for their quantitative determination in human breast milk. The procedure combined protein precipitation with acetonitrile and solid-phase extraction, using Isolute Confirm HCX mixed-mode SPE columns, with minimal matrix effect. The optimum extraction conditions for all three analytes were evaluated using spiked human breast milk, and the recovery exceeded 93.0%. This assay uses methadone-d(9) as internal standard for the determination of methadone and EMDP, and EDDP-d(3) for the determination of EDDP. Calibration curves were linear within the range of 2.00-1000 microg/L for methadone (R(2) > 0.995) and 1.00-500 microg/L for EDDP (R(2) >0.997) and EMDP (R(2) > 0.991). Intra- and interday accuracy and precision were within the range of 0.8-5.7% and 1.3-5.2%, respectively, for all analytes. The stability study was assessed by fortifying human breast milk with methadone and its metabolites at two different concentrations and keeping the samples at different temperature conditions. The analytes were found to be stable in breast milk at room temperature for at least 4 h and at -20 degrees C for at least one month. The method was used for the determination of methadone and its major metabolites in human breast milk samples obtained from women in the postpartum period participating in a methadone maintenance program.     

Extrasynaptic glutamate release through cystine/glutamate antiporter contributes to ischemic damage

During brain ischemia, an excessive release of glutamate triggers neuronal death through the overactivation of NMDA receptors (NMDARs); however, the underlying pathways that alter glutamate homeostasis and whether synaptic or extrasynaptic sites are responsible for excess glutamate remain controversial. Here, we monitored ischemia-gated currents in pyramidal cortical neurons in brain slices from rodents in response to oxygen and glucose deprivation (OGD) as a real-time glutamate sensor to identify the source of glutamate release and determined the extent of neuronal damage. Blockade of excitatory amino acid transporters or vesicular glutamate release did not inhibit ischemia-gated currents or neuronal damage after OGD. In contrast, pharmacological inhibition of the cystine/glutamate antiporter dramatically attenuated ischemia-gated currents and cell death after OGD. Compared with control animals, mice lacking a functional cystine/glutamate antiporter exhibited reduced anoxic depolarization and neuronal death in response to OGD. Furthermore, glutamate released by the cystine/glutamate antiporter activated extrasynaptic, but not synaptic, NMDARs, and blockade of extrasynaptic NMDARs reduced ischemia-gated currents and cell damage after OGD. Finally, PET imaging showed increased cystine/glutamate antiporter function in ischemic rats. Altogether, these data suggest that cystine/glutamate antiporter function is increased in ischemia, contributing to elevated extracellular glutamate concentration, overactivation of extrasynaptic NMDARs, and ischemic neuronal death.     

Metallothionein expression during liver regeneration after partial hepatectomy in cadmium-pretreated rats

Metallothionein is a low molecular mass protein inducible mainly by heavy metals, having high affinity for binding cadmium, zinc and copper. In the present study we investigated the expression of metallothionein in regenerating liver, at different time intervals, in cadmium pretreated partially hepatectomized rats. Liver metallothionein is highly expressed during regeneration in-duced by partial hepatectomy in rats, providing zinc within the rapidly growing tissue. Cadmium pretreatment caused inhibition of the first peak of liver regeneration, while metallothionein expression was markedly more prominent in the liver residues of cadmium-pretreated rats. These results demonstrate that although metallothionein able to bind temporarily metal ions as zinc and cadmium has been highly expressed, the liver regenerative process was inhibited possibly due to the effects of cadmium on other pivotal events necessary to the DNA replication.     

“Poor man’s methadone” can kill the poor man. Extra-medical uses of loperamide: a review

Loperamide is a phenylpiperidine derivative and an opioid agonist that was launched by Janssen Pharmaceutica in 1973. It was initially classified in the United States as a Schedule II drug and was transferred to Schedule V in 1977; it has not been listed as a controlled substance since 1982. Loperamide is used for the symptomatic treatment of diarrhea and gastrointestinal inflammation. It has a low potential for central nervous system effects when administered in therapeutic doses. However, when used in supratherapeutic doses, either for self-treatment or drug abuse (opioid substitute), it can lead to life-threatening cardiac effects. The US Food and Drug Administration and the global community are concerned about these severe side effects, suggesting the need for control worldwide. This article reviews the existing knowledge on loperamide, including its chemistry, synthesis, pharmacology, toxicology, pharmacokinetics, biotransformation, its medicinal use, dependence potential, abuse of the drug, reported intoxications, fatalities, its determinations in biological samples, and its current legal status. All available information was gathered through a detailed search of PubMed and the World Wide Web.     

U-47700. An old opioid becomes a recent danger

U-47700 is a synthetic opioid analgesic and a potent, short acting structural isomer of the earlier opioid AH-7921 that has recently invaded the drug arena in Europe and the Unites States. Although the drug was synthesized and patented in the 1970s, it was first identified in October 2014, as a powder sample that was seized by Swedish Customs. Sweden formally notified the European Union Early Warning System in January 2015. Animal studies proved that U-47700 is a strong μ-opioid receptor agonist and has a morphine-like analgesic action, being 7.5 times higher than morphine. The drug has a much lower affinity for the κ-opioid receptor. This newly appearing psychoactive substance has already led to more than 25 confirmed fatalities associated with U-47700 in Europe and the United States and to six non-fatal intoxications reported in the United States. The aim of this review is to summarize the current knowledge about this drug, regarding its chemistry, synthesis, pharmacology, toxicology and metabolism, as well as its international legal status. The existing analytical methods for the determination of U-47700 in biological samples are also presented. Published or reported U-47700 related cases, fatalities or intoxications, and self reports from drug users are reviewed.