An ab initio and AIM investigation into the hydration of 2-thioxanthine

<p>Abstract</p> <p>Background</p> <p>Hydration is a universal phenomenon in nature. The interactions between biomolecules and water of hydration play a pivotal role in molecular biology. 2-Thioxanthine (2TX), a thio-modified nucleic acid base, is of significant interest as a DNA inhibitor yet its interactions with hydration water have not been investigated either computationally or experimentally. Here in, we reported an <it>ab initio </it>study of the hydration of 2TX, revealing water can form seven hydrated complexes.</p> <p>Results</p> <p>Hydrogen-bond (H-bond) interactions in 1:1 complexes of 2TX with water are studied at the MP2/6-311G(d, p) and B3LYP/6-311G(d, p) levels. Seven 2TX^...H₂O hydrogen bonded complexes have been theoretically identified and reported for the first time. The proton affinities (PAs) of the O, S, and N atoms and deprotonantion enthalpies (DPEs) of different N-H bonds in 2TX are calculated, factors surrounding why the seven complexes have different hydrogen bond energies are discussed. The theoretical infrared and NMR spectra of hydrated 2TX complexes are reported to probe the characteristics of the proposed H-bonds. An improper blue-shifting H-bond with a shortened C-H bond was found in one case. NBO and AIM analysis were carried out to explain the formation of improper blue-shifting H-bonds, and the H-bonding characteristics are discussed.</p> <p>Conclusion</p> <p>2TX can interact with water by five different H-bonding regimes, N-H^...O, O-H^...N, O-H^...O, O-H^...S and C-H^...O, all of which are medium strength hydrogen bonds. The most stable H-bond complex has a closed structure with two hydrogen bonds (N(7)-H^...O and O-H^...O), whereas the least stable one has an open structure with one H-bond. The interaction energies of the studied complexes are correlated to the PA and DPE involved in H-bond formation. After formation of H-bonds, the calculated IR and NMR spectra of the 2TX-water complexes change greatly, which serves to identify the hydration of 2TX.</p

Placebos, placebo effect, and the response to the healing situation: The evolution of a concept

In spite of its impressive progress, medicine has been strongly criticized for relying on its modern biomedical tradition to the neglect of the psychosocial aspects of health. This neglect may account for patients’ dissatisfaction and eventual use of alternative health approaches. The concept of placebo has sustained dramatic ‘’protean” metamorphoses through the ages. For centuries, placebos have been regarded as powerful deceptive therapies. From the middle of the twentieth century, however, conventional medicine has used placebos as methodologic tools to distinguish the specific from the nonspecific ingredients in treatments. In modern medical research, the double-blind, placebo-controlled, randomized clinical trial has been established as the gold standard for the assessment of any new treatment. Recently a new trend regarding placebos seems to have emerged. The placebo and other nonspecific effects elicited by the “healing situation” have been independently subjected to scientific study. Progress in this area may promote useful clinical applications, enabling physicians to broaden their perspectives on the healing process. We present the historical changes of the concept of placebo and the ethical issues raised by their use

Non-pharmacological prophylaxis of affective disorders: A current view with clinical observations in case series of depressed patients

Object: Pharmacotherapy oftentimes proves inadequate in providing satisfactory prophylaxis for affective disorders; thus the need for alternative interventions is obvious. In this observational study, the effectiveness of three non-pharmacological methods employed in patients with recurrent affective illness for prophylaxis in a case series of depressed patients is reported. Method: (a) Electroconvulsive therapy (ECT) was administered twice and later once a month for a period of 2-35 months in nine ECT-recovered depressed patients. (b) Sleep deprivation (SD) was applied once a week for 9-12 months in six SD-recovered depressed patients. W Cognitive therapy (CT)-recovered depressed patients (n=10) received additional CT “booster sessions” every 4 weeks, for 6-8 months. Results: Eight patients in the ECT study and four in the SD study remained in remission during the period of the prophylactic intervention. No significant side-effects for the two methods were observed. Regarding CT, eight patients were not reported as depressed at the 24-month follow-up period. Conclusion: These clinical observations support the current view about the utility of the three non-pharmacological interventions in the prophylaxis of affective disorders, since all methods displayed a satisfactory clinical profile

A survey of the attitudes of Greek medical students toward electroconvulsive therapy

Data on attitudes toward electroconvulsive therapy have been reported from various countries; no information, however, is available from Greece. In this survey, we report the results of a questionnaire reflecting the general attitude of Greek medical students toward ECT. A total of 161 sixth (final)-year medical students who had no previous exposure to a formal didactic experience on ECT, were asked to complete a questionnaire before attending a scheduled 90-minute lecture on ECT, as part of their regular curriculum. Questions in the questionnaire could be grouped to indicate a positive, a reserved, or a negative attitude toward ECT Overall, before the lecture, 50.3% held a positive attitude toward ECT, 43.5% were reserved, and 6.2% held a negative attitude. A subgroup of these students (n = 137) were asked again to score the same questionnaire immediately following the lecture to rate the impact of the didactic seminar. The proportion of students with a positive attitude after the lecture was increased to 78.1%, (P &lt; 0.001), while the proportion of students with reserved and negative attitudes were reduced to 20.4% (P &lt; 0.001) and 1.5%, respectively. These encouraging findings reflect, however, only the immediate effects of the lecture and do not guarantee persistence of this change in attitudes over time

EFFECTS OF METHYSERGIDE AND RITANSERIN ON THE PROLACTIN AND THYROTROPIN RESPONSES TO TRH IN DEPRESSED-PATIENTS

Despite extensive study of the effects of various pharmacological agents on the thyrotropin (TSH) and prolactin (PRL) responses to TRH challenge, the effect of serotoninergic agents remains inconclusive. We studied the effect of the serotonin antagonists methysergide (non-selective 5-HT1/5-HT2 blocker with dopaminergic properties) and ritanserin (selective 5-HT2 blocker) on the TSH and PRL responses to TRH stimulation in two groups of medication-free female depressed patients in a double-blind, within-subject design. Methysergide was found to decrease significantly the PRL response to TRH, while ritanserin had no effect. Neither compound influenced the TSH response. Results suggest that 5-HT2 mechanisms do not mediate the PRL and TSH responses to TRH challenge in depression. The reduction in PRL observed after methysergide is probably due to either 5-HT1 or dopaminergic mechanisms

Thyrotropin-releasing hormone administration does not affect seizure threshold during electroconvulsive therapy

Despite the fact that a role for thyrotropin-releasing hormone (TRH) in seizure modulation has been consistently hypothesized, the exact nature of this role remains unclear. In this study, we investigated the effects of TRH administration on seizure threshold and seizure duration in 13 depressed inpatients undergoing electroconvulsive therapy (ECT). In a balanced order crossover design, an intravenous bolus of 0.4 mg TRH or placebo was administered immediately before anesthesia, during the first two sessions, in a series of bilateral ECT. In both of these sessions, a threshold titration procedure was applied by using gradual increments of the electrical charge delivered until seizure elicitation, a procedure that has been safely used in the past. Seizure threshold was defined as the lowest energy level required for induction of a grand mal seizure, by use of this titration procedure. Seizure duration was estimated both by simultaneous EEG recording and by the cuff method. Results showed that neither seizure threshold, nor seizure duration (either by cuff or by EEG) differed between the TRH and the placebo conditions, regardless of the order in which TRH or placebo were administered in the two ECT sessions. This was the case regardless of whether the patients had at baseline a blunted TSH response to TRH or not. Our findings do not support a role for TRH on seizure modulation, at least when TRH is administered exogenously. Such an effect, if it exists, could be obscured, however, by several factors, including pharmacokinetics

Administration of citalopram before ECT: Seizure duration and hormone responses

From theoretical and clinical perspectives, it is important to know if selected serotonin-reuptake inhibitors (SSRIs), often administered concurrently with electroconvulsive therapy (ECT), modify seizure duration. In a study with a double-blind, cross-over design, the authors evaluated the effect of citalopram, the most selective SSRI available, on the length of electrically induced seizures and on hormone secretion during ECT. Ten depressed women were given either 20 mg citalopram or placebo orally 2 hours before the third and fourth ECT sessions. Seizure duration was assessed by the cuff technique and from electroencephalographic recordings, whereas blood for prolactin, thyrotropin, and cortisol assessment was sampled before ECT and 5, 10, 20, 30, 40, and 60 minutes after ECT. No adverse effects after the administration of citalopram were recorded. The length of seizures was not statistically different in the citalopram (29.3 +/- 8.4 seconds) and placebo sessions (28.2 +/- 9.4 seconds). Neither pre-ECT plasma hormone levels measured 2 hours after citalopram or placebo administration nor the patterns of ECT-induced hormone secretions differed between the two drug and placebo conditions. The lack of effect of citalopram on hormones in this study may be a result of possible deficiencies of the monoaminergic (i.e., serotoninergic) systems in depression. Although safety and efficacy issues were not fully addressed by coadministering citalopram for the long term and throughout the course of ECT, these findings support the view that challenges the typical clinical practice of discontinuing SSRIs before ECT

Blunted TSH response to TRH and seizure duration in ECT

The relationship between the thyrotropin (TSH) response to thyrotropin-releasing hormone (TRH) and the duration of seizures induced by electroconvulsive therapy (ECT) in depressed patients was investigated. In a balanced-order cross-over design, 16 depressed women were given 0.4 mg TRH or placebo intravenously, 20 min before ECT in the first two sessions, In the third ECT session TRH was given just Frier to ECT. Thyrotropin (TSH) levels at various sampling times, as well as the duration of seizures, were measured. There was a significant inverse correlation between plasma TSH concentrations 20 min after TRH administration (Delta TSH) and seizure duration. Furthermore, when patients were categorized according to their TSH response to TRH, the group with blunted responses (Delta TSH &lt; 6 mu IU/mL, n=7) had a longer seizure time during ECT than the group with non-blunted responses (Delta TSH &gt; 6 mu IU/mL, n = 9), Finally, the seizure duration in the group with blunted TSH responses was reduced significantly when TRW. was co-administered, while it remained unchanged in the group with non-blunted TSH responses. It is concluded that a blunted TSH response to TRH might indicate a seizure susceptibility as measured by the duration of seizures induced by ECT. The fact that TRH pre-administration had a reducing effect suggests that this substance might be involved in the pathophysiology of ECT-induced seizures