The aim of this paper is theophylline (THP) inclusion into xanthan-chitosan polyionic complex (Xa-CS) and the study of its in vitro and in vivo kinetic release. Xa-CS hydrogel was obtained by ionic complexation between two oppositely charged polysaccharides. THP was loaded into the Xa-CS matrix by diffusion of the drug solution. The obtained samples were characterized by FTIR spectroscopy, SEM microscopy and study of the swelling behavior. THP in vitro release experiments were carried out in conditions mimicking the gastrointestinal environment. The chosen drug dose for in vivo study was 15 mg THP/Kg body weight of THP powder or an equivalent dose in complex form. THP serum concentrations were determined by an HPLC assay. The THP peak serum concentration (C(max)) was 7.18 microg/ml for free THP and AUC(0-48) was 25.76 microg h/ml, while in the case of Xa-CS-THP, C(max) was of 5.72 microg/ml and AUC(0-48) = 45.72 microg h/ml. The in vivo study regarding the behaviour of the obtained formulation, showed an increase bioavailability of THP compared to the raw drug, suggesting the possible application of the complex Xa-CS as an oral controlled drug delivery system in the management of chronic pulmonary obstructive disease.

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Partial and largely conflicting data are currently available on the interplay between obstructive sleep apnea (OSA) and hypothalamus-pituitary-adrenal axis (HPA) activity in adult obese men. This study was performed to evaluate the daily trajectories of salivary cortisol, specifically with respect to the salivary cortisol awakening response (CAR), a common method used to assess HPA axis activity. The main findings of this study were that adult male obese subjects who were newly diagnosed with severe OSA showed the following: (1) a flattening of the CAR; (2) levels of cortisol at awakening that were lower than those of the controls; and (3) maintenance of the physiological circadian activity of the HPA axis, with the highest hormone concentrations produced in the morning and the lowest in the evening. This study was also designed to investigate the effects of 3 and 6 mos of treatment with continuous airways positive pressure (CPAP). CPAP use resulted in a significant recovery of the sleep patterns disrupted by OSA; moreover, mild neuropsychological signs of depression and anxiety in severe OSA patients were concomitantly progressively improved by CPAP treatment. Furthermore, this study reports that 3 and 6 mos of CPAP therapy restored the presence of CAR and was able to significantly reduce the difference in the morning cortisol levels between the OSA and control groups. In conclusion, we report here that compared with obese nonapneic matched controls, OSA patients present a dysregulation of HPA axis activity, as shown by the flattening of the diurnal pattern of cortisol production in response to repeated challenge due to hypoxia and sleep fragmentation. This dysregulation was especially detectable in the first hour after awakening and restored after 3 and 6 mos of treatment with CPAP.

The main finding was that OSA subjects displayed hypocortisolism upon awakening and a significant reduction in testosterone concentration in the evening in comparison with the control group, which has maintained the physiological testosterone and cortisol diurnal fluctuation, with higher hormone concentrations in the morning and lower concentrations in the evening. The use of data from multiple diurnal measurements rather than a single point allowed the detection of T/C ratio changes of opposite signs at the beginning and end of the day: the OSA subjects had a higher T/C ratio than the controls in the morning, while their T/C ratio was significantly lower than that of the controls in the evening. The imbalances in the anabolic-catabolic diurnal equilibrium suggest that OSA is associated with a dysregulation of the hypothalamic-pituitary-adrenal and hypothalamic-pituitary-gonadal axes, potentially an underlying cause of some of the neuropsychological comorbidities observed in OSA patients.

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BackgroundAwareness about antibiotic resistance depends on the attitudes and information about antibiotic resistance of both patients and physicians. Persons who practice self-medication are at high risk of also self-medicating with antibiotics. The purpose of the present study was to evaluate the awareness about antibiotic resistance by investigating the practice in a group of self-medication users in a sample of adults in Romania and the variables associated with such practice.Material and MethodsA cross-sectional self-filled questionnaire based study was conducted from December 2016 through January 2017 amongst 218 self-medication users (SMUG). The attitudes, the level of knowledge, the perceptions, about antibiotic use (ABU) and about antibiotic resistance (ABR) were compared to a reference group represented by medical residents group in their specialty training (MRG) considered to have a higher level of knowledge and awareness about ABU and ABR.ResultsThe response rate was 87.2% in the SMUG group and 100% in the MRG group. The SMUG group reported self-medication practices for antibiotics with a high frequency at any time in life (72%), but with a very low frequency from the month previous to the date of the study (12%), comparative with the MRG group (75% and 7%, respectively). The multivariate logistic regression analysis showed that self-medication with antibiotics at any time in life in the SMUG group could be predicted by the answers to two questions regarding the practices and knowledge about ABU (Q13 and Q20). On the other hand, in the MRG group, a question about ABR perception (Q23), could be predictor for self-medication with antibiotics. Self-medication with antibiotics in the month previous to the date of the study in the SMUG group could be predicted with three questions: one about ABU practice (Q14), one about ABR perception (Q26) and one referring to ABR knowledge (Q28). On the other hand, in the MRG group, a question about ABR knowledge (Q32) could be predictor for self-medication with antibiotics. The reduced awareness about ABR in the SMUG group, is revealed by the reduced number of subjects (38%), who did not know that missing an antibiotic dose during a medical treatment contributes to ABR, comparative with the MRG group (84%). Indirectly, low ABR awareness in the SMUG group is revealed by the confusion about the appropriate use of antibiotics in bacterial or viral infections (that antibiotics are not used against viruses).ConclusionsThe findings from our study on the awareness about antibiotic resistance in the SMUG group might help the policy makers and regulatory authorities to develop educational programs directed to change the perceptions and attitudes about the appropriate use of antibiotics in order to diminish self-medication practices with antibiotics.

IntroductionZinc chelators were shown to facilitate some opioid-withdrawal signs in animals. Zinc deficiency, which affects more than 15 % the world’s population, is also common among opioid consumers and opioid-treated animals exhibit misbalances of zinc distribution.AimThe present study focuses on how zinc ions interfere with opioid dependence/addiction and analgesia, trying to preliminary discuss if zinc supplementation in opioid-users should be recommended in order to reduce the risk of addiction.MethodsAll relevant literature was searched up to April 2015. The search was performed using the term “zinc” plus combinations of following terms: “opioid receptors”, “opioid” or representatives of this class, “addiction”, “dependence”, “analgesia”, and “pain”. Human, animal, in vitro studies and reviews were including.ResultsBoth human and animal studies revealed decreased serum zinc under opioid-administration conditions, attributed mainly to increased urinary elimination (humans) or redistribution (animals). Moreover, animal studies revealed decreased brain zinc levels in morphine-treated animals, with increased zinc hepatic levels, but also an enhancement of endogenous opioid system activity and a possible reduction of morphine withdrawal by zinc. In vitro studies revealed reduction of opioid ligands binding to receptors by zinc. However, the very few in vivo animal studies on opioid analgesia revealed controversial results, as zinc demonstrated clear analgesic effect, but zinc associated to opioids doesn’t result in a potentiation of the analgesic effect.ConclusionZinc dietary supplementation in patients treated with opioids for cancer-related chronic pain should be considered, due to the high incidence of zinc deficiency, also well-documented in opioid consumers. The low toxicity of orally-administered zinc also pleads for this idea. The main contra-argument to zinc administration in opioid-treated persons is related to the way zinc influences opioid-induced analgesia.