Circulatory Activities of Some 2-Imidazoline Derivatives in Wistar Rats

Wstęp Pochodne 2-imidazoliny stanowią ważną grupę leków przeciwnadciśnieniowych o ośrodkowym mechanizmie działania. Celem pracy było otrzymanie wielu analogów znanych imidazolin typu klonidyny i lofeksydyny, zbadanie ich struktury oraz określenie wpływu na ciśnienie tętnicze krwi i częstość akcji serca szczurów szczepu Wistar. Materiał i metody Oznaczenie wpływu analogów a-hydroksylowych (1a-g) i 2-aminowych (2a-d) 2-aryloiminoimidazolin oraz N-benzylo-N-(4,5-dihydro- -1H-imidazol-2-ylo)-metoksyloaminy (3) na średnie ciśnienie tętnicze krwi i częstość akcji serca prowadzono na szczurach normotensywnych, samcach rasy Wistar o masie 220–370 g. Pomiarów ciśnienia skurczowego krwi dokonywano metodą krwawą. Rejestrowano odpowiedź presyjną na każdorazową podaną dawkę związku imidazoliny. Pomiar częstości akcji serca u szczurów wykonywano, zliczając wychylenia słupa krwi tętniczej w jednostce czasu. Wychylenia rejestrowano poprzez dotętniczą kaniulę polietylenową (liczba wychyleń/min). Wyniki Wykazano zróżnicowany i zależny od struktury wpływ badanych pochodnych 2-imidazoliny na ciśnienie tętnicze krwi i częstość akcji serca po podaniu dożylnym. W grupie połączeń hydroksyloaminy największą aktywność wykazał związek 1b, zawierający grupę metylową w pozycji 4 pierścienia fenylowego (ED50 = 0,17 mg/kg). Pochodne o-fenylenodiaminy typu 2, w zależności od charakteru lipofilowego, działały hipo- (2a i 2b) lub hipertensyjnie (2c i 2d). Na podstawie badania rentgenograficznego tiocyjanianu 2e wykazano, iż związki te posiadają cechy strukturalne odpowiadające ligandom receptorów a2-adrenergicznych. Natomiast analog lofeksydyny (3), zawierający ugrupowanie N-metoksylowe w łańcuchu bocznym, okazał się nieaktywny w dawkach sięgających 2 mg/kg. Wnioski Przyłączenie grupy hydroksylowej do egzocyklicznego atomu 2-aryloiminoimidazolin nie pozbawia tych związków działania hipotensyjnego. Działanie analogów zawierających grupę aminową w położeniu 2 pierścienia aromatycznego zależy od ich charakteru lipofilowego. Można przypuszczać, iż większa lipofilowość pochodnych 2c i 2d w porównaniu z 2a i 2b umożliwia tym związkom przenikanie bariery krew-mózg i blokowanie ośrodkowych receptorów a2-adrenergicznych, co objawia się działaniem hipertensyjnym.Background 2-aryliminoimidazolines constitute a valuable class of centrally acting antihypertensive drugs. The aim of our studies was to evaluate effects of some analogues of clonidine and lofexidine on the arterial blood pressure and heart rate in Wistar rats following i.v. administration. Material and methods Effects of a-hydroxy (1a-g) and 2-amino (2a-d) analogues of clonidine and N-benzyl-N- -(4,5-dihydro-1H-imidazol-2-yl)-methoxylamine (3) on the mean arterial blood pressure and heart rate were determined in normotensive, male Wistar rats weighting 220–370 g. The experiments were performed using animals anaesthetized with urethane and tracheotomized. Results Compounds 1a-g showed hypotensive activity accompained by a positive chronotropic effect with 1b being the most active (ED50 = 0,17 and 0,145 mg/kg respectively). Among the 2-amino-phenyliminoimidazolines of type 2, the more hydrophilic 2a and 2b exhibited relatively weak hypotensive effects, while the more hydrophobic analogues 2c and 2d were shown to possess remarkable hypertensive activities at doses 0,25 mg/kg. X-ray crystal structure analysis of the thiocyanate salt 2e confirmed geometrical features required for good ligand interaction at the a2-adrenergic receptors. On the other hand, N-benzyl-N-(4,5-dihydro-1H-imidazol-2-yl)-methoxylamine 3was not active at doses up to 2 mg/kg. Conclusions The introduction of the hydroxyl group on the exocyclic nitrogen atom of 2-aryliminoimidazolines afforded compounds retaining much of the hypotensive activity. On the other hand, cardiovascular activity of the analogues containing 2-amino substituent at the phenyl ring depends strongly on their lipophilic character. It can be presumed that penetration of the more lipophilic 2c and 2d into the CNS enables these compounds to block a2-adrenergic receptors which results in an increased blood pressure

Study program on opinions of schizophrenic patients treated with antipsychotics

Wstęp. Brak współpracy pacjenta w leczeniu jest jedną z najczęstszych przyczyn przerywania leczenia i braku skuteczności terapii zaburzeń psychicznych. Wiele czynników może mieć wpływ na niestosowanie się pacjentów do zaleceń lekarskich, na przykład rodzaj schorzenia, zjawisko stygmatyzacji chorobą psychiczną i jakość relacji pacjent–lekarz. Celem badania była ocena opinii pacjentów leczonych lekami przeciwpsychotycznymi nowej generacji. Materiał i metody. Badaniem objęto grupę 1400 pacjentów schizofrenicznych, leczonych ambulatoryjnie jednym z leków przeciwpsychotycznych drugiej generacji. Wyniki. Pacjenci uważali, że najważniejszymi objawami, na których ustąpienie zwracają szczególną uwagę, są: lęk i napięcie, urojenia i omamy. Wśród objawów niepożądanych neuroleptyków pacjenci zwracali największą uwagę na senność, zaburzenia seksualne, otyłość i objawy pozapiramidowe. Ponad 80% pacjentów leczonych nowoczesnymi neuroleptykami chciało leczyć schizofrenię; 82% pacjentów uważało, że stosowanie leków przeciwpsychotycznych powoduje objawy niepożądane. 81% pacjentów uważało, iż stosowanie leku przeciwpsychotycznego poprawia ich poziom funkcjonowania w społeczeństwie i rodzinie; 74% pacjentów schizofrenicznych obawiało się objawów niepożądanych leków przeciwpsychotycznych, a 70% nie mówiło innym, że pobierają lek przeciwpsychotyczny; 77% pacjentów twierdziło, że leczenie schizofrenii jest skuteczne. Nie więcej niż 40% pacjentów czuło się źle lub nienaturalnie, stosując nowoczesny lek przeciwpsychotyczny. Wnioski. Pacjenci leczeni lekami przeciwpsychotycznymi drugiej generacji mogą odznaczać się dobrą współpracą. W opinii pacjentów, najważniejsze w leczeniu schizofrenii jest ustąpienie objawów wytwórczych i objawów afektywnych. Najbardziej kłopotliwymi objawami niepożądanymi neuroleptryków są: sedacja, zaburzenia seksualne, otyłość i objawy pozapiramidowe. Zjawisko stygmatyzacji pacjenta jest powszechne w grupie osób ze schizofrenią.Introduction. Noncompliance is one of most frequent reasons of discontinuation of therapy and lack of effectiveness of psychiatric disorders treatment. Many factors may influence on noncompliance, e.g. type of disease, phenomenon of stigmatization with mental disease and quality of patient-doctor relation. The study aimed to explore opinions of patients treated with new generation antipsychotics. Material and methods. One thousand four hundred out-patients treated with one of second generation antipsychotics were studied. Results. Patients considered anxiety, tension, delusions and hallucinations the most important symptoms to be released from. Most attracting neuroleptic side effects were drowsiness, sexual dysfunctions, obesity and extrapyramidal symptoms. More than 80% of patients treated with modern neuroleptics wanted to treat schizophrenia; 82% patients thought that the treatment with atipsychotics produces side effects. In opinion of 81% of subjects level of family and society functioning was improved by intake of antipsychotics; 74% patients worried about side effects of antipsychotics and 70% did not tell nobody they take antipsychotic drug; 77% of patients claimed that schizophrenia treatment is effective. No more than 40% of patients felt bad or unnatural using antipsychotic drug. Conclusions. Patients treated with second generation antipsychotics may be characterized with good compliance. In opinion of patients most important in the treatment of schizophrenia are productive and affective symptoms. Most interfering side effects of neuroleptics are sedation, sexual dysfunctions, obesity and extrapyramidal symptoms. Stigmatization phenomenon is abundant in the examinated group of people with schizophrenia

RISK FACTORS FOR NONCOMPLIANCE WITH ANTIPSYCHOTIC MEDICATION IN LONG-TERM TREATED CHRONIC SCHIZOPHRENIA PATIENTS

Background: The attitudes of schizophrenic patients toward medications directly impact the treatment compliance. Although noncompliance represents a serious concern in long-term schizophrenia treatment, a detailed information on the factors that impair compliance is still limited. The present study aims to assess the factors related to noncompliance with antipsychotics agents, in longterm treated chronic paranoid schizophrenia patients. Subjects and methods: Two groups of such patients (total number n=162) were analyzed and compared: 1). patients with symptomatic remission on haloperidol (n=32), clozapine (n=40) or olanzapine (n=45), and 2). drug resistant patients (n=45). The mean duration of the disease was 19.3 years. Results: Altogether, in our patient sample, a better drug attitude was found in the olanzapine and clozapine groups. Our findings have also revealed that worse attitude toward antipsychotics correlated with an earlier onset of schizophrenia, younger patient age, shorter duration of the disease, higher burden of symptoms, treatment with a typical antipsychotics, and higher severity of akathisia. Conclusion: Our results suggest that detecting factors that influence the patient’s attitude toward medications might be helpful for designing targeted educational strategies in chronic schizophrenia patients (particularly those with the high risk of noncompliance), and further trials are warranted to explore this topic

DEPRESSION, SLEEP DISTURBANCES AND ANXIETY IN PATIENTS WITH RELAPSING-REMITTING MULTIPLE SCLEROSIS: A LONGITUDINAL COHORT OBSERVATION

Background: Depression, sleep disturbances and anxiety may affect almost half of the population of patients with multiple sclerosis (MS) and they are major determinants of poor quality of life in young adults. The aim of our study was to assess their incidence in patients with MS in Poland, and whether they change during longitudinal observation in routine clinical practice. Subjects and methods: We included 53 consecutive patients with relapsing-remitting form of MS in this prospective study, who were treated in our department. All patients were examined at the entry to the study and after at least three or more years after study start with 4 standardized questionnaires and clinical scales that were validated in Polish patients: Athens Insomnia Scale (AIS), Epworth Sleepiness Scale (ESS), Hospital Anxiety and Depression Scale (HADS) and Expanded Disability Status Scale (EDSS). The data from the two time-points were compared. Results: At the entry to the study daytime sleepiness, nighttime insomnia, depression episodes and anxiety were observed in 11.3%, 13.2%, 11.3% and 28.3% of patients, respectively. At the end of the study higher proportion of patients reported any form of drowsiness, depression, insomnia or anxiety, however, the differences were not statistically significant. Except for anxiety, higher proportion of patients reported definite disorders, with the rise from 3.8% to 13.2% having depression and rise from 9.4% to 15.1% having insomnia. Moderate or pathological drowsiness was not reported initially, but it was reported in 5% and 2.5% patients, respectively, at the study end. Conclusions: The incidence of sleep and mood disturbances in polish patients with MS is quite high, and it is comparable to other studies in patients with MS. Possible mood changes or sleep disturbances in individual patients should be routinely monitored by clinicians

IMPLEMENTATION OF THE MOTEK CAREN SYSTEM IN BEHAVIOURAL THERAPY FOR PATIENTS WITH ANXIETY DISORDERS

Background: Virtual reality exposure therapy (VRET) is becoming a more and more popular treatment method for patients suffering from anxiety disorders. One of the VRET methods, wchich could be used for this group of patients is MOTEK CAREN system, however, so far no studies have been published on its implementation in psychiatric disorders. Subject and methods: Presented here is a case of a 45 year old woman suffering from anxiety disorders, who underwent a series of four subsequent trainings with the use of MOTEK CAREN system repeted once a week. Data from the system were collected on the work of muscles, joints, reactions of the ground, etc. Blood pressure, pulse and salivary cortisol level were measured before and after each training. The level of state and trait anxiety was each time measured with the STAI inventory. Results: The changes of the values of heart rate, blood pressure and salivary cortisol suggest that all trainings we stressful events for the patients, as they were not observed in the control session. But the gradual decrease in the levels of salivary cortisol and axiety as state after subsequent trainings may be signs of a gradual adaptation of the patient to the stressful situation. A lower cadence during the trainings compared to the control session was observed, however the speed of the cadence increased with each session. Conclusions: Ttrainings with the MOTEK CAREN system can be promising in the treatment of anxiety disorders. Of course in order to draw more evidence based conclusions this observations must be confirmed on a larger sample of patients

Mechanics of the Society Mythologen

Połączenie wiedzy z dziedziny medycyny i fizyki kwantowej stworzyło elegancki i spójny model zjawiska świadomości zwany modelem Orch. OR. Zgodnie z tym modelem mózg działa jak żywa maszyna kwantowa, oparta na kompleksach mikrotubul. Zjawiska kwantowe w mikrotubulach umożliwiają doświadczanie qualiów w rzeczywistości Plancka. Qualia mają analogie w innych, omówionych w artykule teoriach współczesnej nauki. Odnoszą się do pól energetycznych — atraktorów, organizujących spostrzeganie, emocje i intelekt. W artykule przedstawiono implikacje społeczne dziedziczenia pól atraktorowych i ich wpływu na świadomość społeczną.The fusion of knowledge from the fields of medicine and quantum physics formed the elegant and consistent model of phenomenon of consciousness, called Orch. OR model. According to this model the brain works as a live quantum machine, based on complexes of microtubules. Quantum phenomena in microtubules allow experiencing qualia in the Planck’s reality. Qualia have analogies in another theories of contemporary science, described in the article. Qualia relate to energetic fields — atractors, which organize the perception, emotions and the intellect. The article presents society implications of inheritance of atractor fields and their influence on society consciousness

Selected neurological complications of oncological treatment — literature overview

Treatment in oncology may lead to several adverse side effects, including those affecting the nervous system. These side effects may reduce the quality of life of patients, both during and after treatment, and may necessitate changes in the treatment regimen or reduction of drug doses, thus reducing the effectiveness of therapy. The knowledge of therapy-induced side effects is essential for their early recognition and differentiation from symptoms resulting from the progression of neoplastic disease, metabolic disorders, or infections, requiring prompt initiation of causal treatment. This article presents the current state of knowledge regarding central and peripheral neurotoxicity of treatment in oncology. Adverse effects described after chemo- and radiotherapy are better known but still limit the potential possibilities of the applied treatment. Neurotoxicities of targeted therapy and immunotherapy, which are of increasing importance in the era of personalization of treatment, are presented

Compulsive buying — new therapeutic challenge

Kompulsywne zakupy z powodu dużej częstości występowania w społeczeństwie zasługują na większą uwagę psychiatrii. Kompulsywne kupowanie jest kandydatem na kolejne uzależnienie czynnościowe. Problem ten jest badany od wielu lat, ciągle jednak wiele pytań pozostaje bez odpowiedzi. Autorzy przedstawiają charakterystykę tego zaburzenia oraz przegląd metod leczenia.Due to its high population prevalence the compulsive buying deserves more attention from psychiatrists. Compulsive buying is the candidate for another functional dependence. This problem is studied for many years, but still remains a lot of unanswered questions. The authors present the characteristics of this disorder and an overview of studied methods of treatment

Multiple sclerosis: oral health, behaviours and limitations of daily oral hygiene — a questionnaire study

Clinical rationale for the study. Neurological deficits and progressing disability in patients with multiple sclerosis (MS) may hamper daily oral hygiene, but their relations with oral problems have not yet been clearly determined.Aim of the study. The aim of this study was to identify the most significant dental problems and limitations of daily oral hygiene in Polish patients with MS.Material and methods. 199 patients with diagnosed MS (median age 37 years) treated in the neurological outpatient clinic were interviewed using a paper-based questionnaire. They provided answers on oral health, behaviours and the limitations of their daily oral hygiene. Clinical information regarding symptoms, MS phenotype, relapses, medication and degrees of disability was based on medical records.Results. The most frequent symptoms were dry mouth (43.2%) and bleeding from gums (28.1%). Dry mouth was more frequent in patients with secondary-progressive MS (SPMS) than relapsing-remitting MS (65.4% vs 41.3%, p = 0.023). Patients with bleeding from gums had had MS for a longer duration (median 6 vs 4 years, p = 0.002). Difficulties in daily oral hygiene were more frequent in patients with SPMS (24.0% vs 8.1%; p = 0.016). Greater proportions of patients with muscle weakness of limbs, imbalance or pain brushed their teeth irregularly. Frequent (i.e. at least every six months) visits to the dentist’s surgery were uncommon in patients with SPMS (12.0% vs 39.7%, p = 0.010).Conclusions and clinical implications. Dry mouth and bleeding from gums are more frequent in patients with longer lasting and more advanced types of MS. Daily oral hygiene and oral health self-control is limited in patients with MS, mainly due to motor deficits, balance problems and pain, and this becomes worse with disease duration. To minimise the burden of the disease, patients with MS require better education and improvement in their awareness regarding proper oral health control, such as the use of electric toothbrushes. In addition, patients with chronic and progressive disability from multiple sclerosis may benefit from better organised access to dental care