Tooth Decay Prevalence among Children with Somatotropin Hypopituitarism

The malfunction of pituitary gland can be one of the factors disturbing the growth and development of long bones and may have the adverse effect on the development of maxilla, mandible and dentition in children. The aim of the study was to assess the state of dentition by dental caries prevalence among children with short stature in comparison to healthy children. The examined group comprised 110 children who were hospitalized due to growth hormone deficiency and the control group consisted of 41 generally healthy children. To assess the condition of the teeth the mean DMFT index for permanent dentition and dmft index for primary dentition were used. In patients with short stature, the mean DMFT index was 5.0 and in the control group the mean DMFT index was 4.37. In patients with short stature, the average dmft index was 3.37 and in the control group, the mean dmft was 3.39. The prevalence of dental caries for permanent and milk dentition did not differ significantly between the group of children with growth hormone deficiency and the control group

The 1,3,5-triazine derivatives as innovative chemical family of 5-HT6 serotonin receptor agents with therapeutic perspectives for cognitive impairment

Among serotonin receptors, the 5-HT6 subtype is the most controversial and the least known in the field of molecular mechanisms. The 5-HT6R ligands can be pivotal for innovative treatment of cognitive impairment, but none has reached pharmacological market, predominantly, due to insufficient “druglikeness” properties. Recently, 1,3,5-triazine-piperazine derivatives were identified as a new chemical family of potent 5-HT6R ligands. For the most active triazine 5-HT6R agents found (1-4), a wider binding profile and comprehensive in vitro evaluation of their drug-like parameters as well as behavioral studies and an influence on body mass in vivo were investigated within this work. Results indicated the most promising pharmacological/druglikeness profiles for 4-((1H-indol-3-yl)methyl)-6-(4-methylpiperazin-1-yl)-1,3,5-triazin-2-amine (3) and 4-((2-isopropyl-5-methylphenoxy)methyl)-6-(4-methylpiperazin-1-yl)-1,3,5-triazin-2-amine (4), which displayed a significant procognitive action and specific anxiolytic-like effects in the behavioral tests in vivo together with satisfied pharmaceutical and safety profiles in vitro. The thymol derivative (4) seems to be of higher importance as a new lead candidate, due to the innovative, non-indole and non-sulfone structure with the best 5-HT6R binding properties

Tętniaki mózgu - współczesne metody leczenia wewnątrznaczyniowego

Tętniaki tętnic wewnątrzczaszkowych to najczęstszy rodzaj wad naczyniowych mózgu. Pęknięcie tętniaka powoduje samoistny krwotok podpajęczynówkowy. W piśmiennictwie są liczne publikacje dotyczące patogenezy tętniaków. Przez wiele lat jedynym sposobem leczenia tętniaków tętnic mózgowych było postępowanie operacyjne. Jedną z metod leczenia wewnątrznaczyniowego wykorzystywaną przez radiologów zabiegowych jest embolizacja za pomocą spiral (terapia wewnątrznaczyniowa). Wielkim krokiem, który zrewolucjonizował wewnątrznaczyniowe leczenie tętniaków mózgu, było zastosowanie w styczniu 1991 roku przez Guido Guglielmi spiral odczepialnych. Metoda embolizowania za pomocą spiral jest wciąż udoskonalana. Prowadzone są też wieloośrodkowe badania, które mają potwierdzić jej skuteczność. Dużym problemem w leczeniu spiralami platynowymi jest dokładne, gęste wypełnienie worka tętniaka spiralami i rekanalizacja. Możliwość precyzyjnej oceny objętości tętniaka za pomocą stacji 3D cyfrowej angiografii subtrakcyjnej ma zastosowanie praktyczne w ocenie skuteczności długoterminowego leczenia wewnątrznaczyniowego tętniaków wewnątrzczaszkowych. Rozwój nowych technologii wewnątrznaczyniowych w leczeniu tętniaków pozwala na osiągnięcie lepszych wyników terapeutycznych. Polski Przegląd Neurologiczny 2010; 6 (1): 22–2

Computer-Aided Studies for Novel Arylhydantoin 1,3,5-Triazine Derivatives as 5-HT6 Serotonin Receptor Ligands with Antidepressive-Like, Anxiolytic and Antiobesity Action In Vivo

This study focuses on the design, synthesis, biological evaluation, and computer-aided structure-activity relationship (SAR) analysis for a novel group of aromatic triazine-methylpiperazines, with an hydantoin spacer between 1,3,5-traizine and the aromatic fragment. New compounds were synthesized and their affinities for serotonin 5-HT6, 5-HT1A, 5-HT2A, 5-HT7, and dopamine D2 receptors were evaluated. The induced-fit docking (IFD) procedure was performed to explore the 5-HT6 receptor conformation space employing two lead structures. It resulted in a consistent binding mode with the activity data. For the most active compounds found in each modification line, anti-obesity and anti-depressive-like activity in vivo, as well as “druglikeness” in vitro, were examined. Two 2-naphthyl compounds (18 and 26) were identified as the most active 5-HT6R agents within each lead modification line, respectively. The 5-(2-naphthyl)hydantoin derivative 26, the most active one in the series (5-HT6R: Ki = 87 nM), displayed also significant selectivity towards competitive G-protein coupled receptors (6–197-fold). Docking studies indicated that the hydantoin ring is stabilized by hydrogen bonding, but due to its different orientation, the hydrogen bonds form with S5.44 and N6.55 or Q6.58 for 18 and 26, respectively. Compound 26 exerted anxiolytic-like and antidepressant-like activities. Importantly, it demonstrated anti-obesity properties in animals fed palatable feed, and did not show toxic effects in vitro

Are the hydantoin-1,3,5-triazine 5−HT6R5-HT_{6}R ligands a hope to a find new procognitive and anti-obesity drug? : considerations based on primary in vivo assays and ADME-Tox profile in vitro

$5-HT_{6}R$ Though the $5-HT_{6}R$ serotonin receptor is an important target giving both agonists and antagonists similar therapeutic potency in the treatment of topic CNS-diseases, no $5-HT_{6}R$ ligand has reached the pharmaceutical market yet due to the too narrow chemical space of the known $5-HT_{6}R$ agents and insuffcient "drugability." Recently, a new group of non-indole and non-sulfone hydantoin-triazine $5-HT_{6}R$ ligands was found, where 3-((4-amino-6-(4-methylpiperazin-1-yl)- 1,3,5-triazin-2-yl)methyl)-5-methyl-5-(naphthalen-2-yl)imidazolidine-2,4-dione (KMP-10) was the most active member. This study is focused on wider pharmacological and "druglikeness" characteristics for KMP-10. A computer-aided insight into molecular interactions with $5-HT_{6}R$ has been performed. "Druglikeness" was examined using an eight-test panel in vitro, i.e., a parallel artificial membrane permeability assay (PAMPA), and Caco-2 permeability-, P-glycoprotein (Pgp) affnity-, plasma protein binding-, metabolic stability- and drug–drug interaction-assays, as well as mutagenicity- and HepG2-hepatotoxicity risk tests. Behavioral studies in vivo, i.e., elevated plus-maze (EPM) and novel object recognition (NOR) tests, were performed. Extended studies on the influence of KMP-10 on rats' metabolism, including biochemical tests, were conducted in vivo. Results indicated significant anxiolytic and precognitive properties, as well as some anti-obesity properties in vivo, and it was found to satisfy the "druglikeness" profile in vitro for KMP-10. The compound seems to be a good lead-structure and candidate for wider pharmacological studies in search for new CNS-drugs acting via $5-HT_{6}R$

Doświadczanie stresu przez osoby z otyłością - badania własne

WSTĘP. Stres może być czynnikiem wywołującym potrzebę jedzenia, a jedzenie ze względu na swoją dostępność jest prostym sposobem zmniejszenia napięcia. Celem badań jest analiza doświadczania stresu przez osoby z otyłością. MATERIAŁ I METODY. Badaniem objęto 117 pacjentów leczonych z powodu otyłości (śr. wieku: 50 lat, śr. BMI = 34,5) oraz 107 osób w grupie kontrolnej. Badani wypełniali Kwestionariusz Oceny Stresu analizujący sytuacyjną i dyspozycyjną ocenę stresu. WYNIKI. W grupie badanej sytuacja leczenia (sytuacyjna ocena stresu) jest postrzegana jako bardziej zagrażająca (12,2 vs. 6,7; p < 0,000) i krzywdząca (5,9 vs. 3,3; p < 0,000), stanowiąca większe wyzwanie do aktywności (9,5 vs. 7,6; p < 0,000), lecz z małymi szansami na zmianę (4,0 vs. 8,2; p < 0,000) w porównaniu z grupą kontrolną. Podobnie, w zakresie oceniania różnych trudnych sytuacji, osoby otyłe bardziej postrzegają je jako zagrażające (11,9 vs. 7,2; p < 0,000), krzywdzące (6,3 vs. 4,6; p < 0,000) i mniej optymistyczne (4,4 vs. 6,1; p < 0,000) niż grupa kontrolna. WNIOSKI. W doświadczaniu sytuacji stresu osoby otyłe są bardzo obciążone psychicznie, a jedzenie może być formą zmniejszenia napięcia. Dlatego programy leczenia otyłości powinny mieć charakter kompleksowej terapii, uwzględniającej kształtowanie umiejętności efektywnego radzenia sobie ze stresem

Monitoring of tacrolimus concentration after kidney or heart transplantation - the importance of intra-subject variability parameters

Background. Properly managed immunosuppression in post-transplant therapy is a necessary for minimizing the risk of organ rejection. Aim of the study. Steady-state tacrolimus (TAC) trough concentration (Cssmin) analysis in the first month following heart or kidney transplantation. The intra-individual coefficient of variation (CV) was calculated, correlations with biochemical parameters were searched and recommendations/current guidelines for optimizing TAC dosing based on evidence-based medical databases (EBM) were presented. Material and methods. 24 patients aged 24-79 years (mean 47,1±13,9 years) were selected for retrospective analysis; 12 after heart transplant and 12 after kidney transplant. TAC dosing was the same in the patient groups and did not change during the analysis (first month); in heart recipients it was 2 mg/day and 1 mg/day in kidney recipients. Whole blood Cssmin TAC (steady state) was measured four times in all patients; the first in the 15th day of treatment, the second in 16-18, the third in 17-19, the fourth in 18-21. The QMS Tacrolimus immunoassay was used to analyze TAC concentration using the Indiko Plus automated chemistry analyzer. Results. The median Cssmin TAC value was 6,9-15,6 ng/mL after heart transplant and 8,7-16,0 ng/mL after kidney transplant. The CV range of patients after heart transplantation was 4-60%, while after kidney transplantation it was 8-40%. CV>30% (a higher risk of acute rejection) after heart transplant concerned 25% of patients and 15% after kidney transplant. The analysis of organ survival in heart and kidney recipients showed 83% and 100%, respectively, at an average of 2,7±0,5 and 3,25±2,5 years after transplantation. There were no significant correlations (p>0,05) between CV and selected biochemical parameters. Conclusion. CV>30% may indicate a large variability in the pharmacokinetics of TAC and thus, the need to optimize the dosage/physiological parameters affecting its concentration values. It seems necessary to improve the personalization of immunosuppressive therapy with TAC, taking into account individual parameters of extra- and intra-individual variability, in order to obtain better therapeutic results and avoid acute/chronic rejection, accelerated in time of organ transplant loss and/or the occurrence of additional side effects of TAC