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It has been shown in electrophysiological studies that the ligand L-655,708 possesses a binding selectivity and a moderate inverse agonist functional selectivity for α5-containing GABA-A receptors. The present study is aimed to investigate the antidepressant effects of the ligand L-655,708 in the forced swim test (FST) and its impact on locomotor activity in rats. The behavior of the animals was recorded with a digital camera, and the data were analyzed by one-way ANOVA, followed by Dunnett’s test. In FST, L-655,708 significantly decreased immobility time at a dose of 3 mg/kg after a single and repeated administration (p0.05). These data suggest that negative modulation at GABA-A receptors containing the α5 subunit may produce antidepressant effects in rats. These effects were not confounded by locomotor influences.

Introduction. Incontinentia pigmenti (IP) is a rare X-linked dominant genodermatosis. Mutations of the IKBKG gene are the only known cause of IP. The presence of other than skin changes is important in the diagnosis of atypical IP cases when skin changes are discrete. Objective. The study was designed to analyze clinical manifestation, family histories and the frequency of IKBKG gene mutation in IP patients in Serbia for the first time and to compare them with other reported findings. Methods. Two Serbian unrelated families with eight female subjects were investigated. Blood samples were used for IKBKG exon 4-10 deletion testing using modified PCR protocol. For probands pathohistological and ultrastructural analyses of skin biopsies were done. Results. Positive clinical diagnosis according to IP criteria was present in seven cases. In six of them, including probands, positive molecular gene testing for IKBKG exon 4-10 deletion was present. Conclusion. This is the first report of genetically confirmed IP in two Serbian families. The IP patients presented a common IKBKG exon 4-10 deletion. The frequency and type of IKBKG mutation found in investigated IP patients in Serbia were similar to results of other studies. Various clinical features of investigated patients have allowed us to demonstrate that molecular genetic testing which specifically detects the common IKBKG mutations, the only known cause of IP, is useful in diagnosing IP especially in mild or atypical cases. The molecular genetic testing of the IKBKG mutations may be helpful for rapid confirmation of IP diagnosis, prenatal diagnosis and carrier detection.

Background/Aim. Zinc is an essential element which has considerable interaction with gamma-aminobutyric acid A type receptors (GABAA) and glutamate receptors in the central nervous system (CNS). It is believed that zinc acts as a potent inhibitor of glutamate N-methyl-D-aspartate (NMDA) receptors, and binding to structurally specific site on the GABAA receptor leads to inhibition of GABA dependent Cl-pass. The aim of our research was to test the anxiolytic and antidepressant effects of zinc after single application and its influence on general behavioural parameters after repeated administration. Methods. Male Wistar rats were treated with increasing doses of zinc histidine dehydrate (10, 20, 30 mg/kg, i.p.). To determine anxiolytic and antidepressant properties of zinc two models were used: elevated plus maze (EPM) and forced swim test (FST). Behavioural parameters (stillness and mobility) were, also, recorded after single and repeated administration of active substance. Results. Testing animals in the EPM showed a statistically significant difference as follows: dose of 20 mg/kg significantly increased the time animals spent in open arms, indicating an acute anxiolytic effect, while doses of 30 mg/kg significantly reduced the time in the open arms, indicating a potentially anxiogenic effect. Testing the animals by FST showed a statistically significant difference in immobility time of animals treated with the lowest applied (10 mg/kg) and highest applied (30 mg/kg) doses of zinc, compared to the control group. The first day of testing behavioral parameters showed the tendency to increase locomotor activity of the animals with the lowest dose of zinc (10 mg/kg), while the following day revealed a reduced activity with the highest dose applied (30 mg/kg). Conclusion. Zinc has important effects on the CNS: After single application, in all doses zinc showed antidepressant effects. The effects of zinc on anxiety and locomotor activity showed dose-dependent bidirectional effects. [Projekat Ministarstva nauke Republike Srbije, br. 175076]

Introduction. Incontinentia pigmenti (IP) is a rare X-linked dominant genodermatosis. Mutations of the IKBKG gene are responsible for IP. A deletion of exons 4-10 can be found in 80% of patients with IP. There are 69 different mutations of the IKBKG gene that have been reported. Case Outline. A proband, female patient from a family without previously diagnosed IP is reported. She had skin and dental changes typical of IP. The diagnosis was made according to updated IP criteria. Pathohistological and ultrastructural analysis of skin biopsy confirmed the diagnosis. However, the common deletion of exons 4-10 in the IKBKG gene could not be detected. Sequencing revealed the indel (deletion/insertion) mutation c.641_647delGCATGGAinsAT (p.Arg214HisfsX38) in exon 5 of the IKBKG gene. Because this mutation could not be detected in the unaffected mother of the proband, it seems to be a de novo mutation. Conclusion. The registered novel frameshift IKBKG mutation c.641_647delGCATGGAinsAT (p.Arg214HisfsX38) can be considered to be the cause of IP in this case. [Projekat Ministarstva nauke Republike Srbije, br. 175005]

Magnesium (Mg) is an essential element that catalyses more than 300 enzyme systems. Its effects on the central nervous system are exhibited through the blocking of activity of N-methyl D-aspartat (NMDA) receptors and potentiating of GABA-ergic neurotransmission. Due to the vast importance of these two neurotransmission systems in the fine regulation of the central integrative function activity, the aim of this research was to test the anxiolytic and antidepressive effects of magnesium, after acute and repeated application, and its influence on general behavioural parameters. In this research Wistar albino rats were treated with increasing doses of Mg chloride 6-hydrate (MgCl 10, 20, 30 mg/kg). In order to determine anxiolytic and antidepressive properties of magnesium two models were used: elevated plus maze (EPM) and forced swim test (FST). Behavioural parameters (stillness and mobility) were recorded during acute and repeated administration of the active substance. Results of EPM testing showed no significant difference between groups, p>0.05. After acute application of increasing doses of magnesium chloride hydrate in FST, we showed the statistically significant difference in immobility time between the group of animals treated with Mg and the control group treated with the solvent, p

Background/Aim. During peritoneal dialysis (PD) an exchange of substances between blood and dialysate takes place through specific histological structures of peritoneum. Peritoneal double-layered serous membrane has, so far, mostly been studied with electron microscopy on experimental animals. The aim of this study was to assess integrity of peritoneal tissue in end-stage renal disease (ESRD) and PD patients using standard light microscopy and immunohistochemical methods. Methods. Peritoneal tissue biopsies were performed on 25 persons: 8 healthy donors during nephrectomy, 9 ESRD patients upon insertion of PD catheter, and 8 PD patients upon removal of the catheter for medical indications. The samples were fixed and prepared routinely for immunocytochemical staining by standardized streptavidin biotin AEC method using a LSAB2® HRP kit (Dako®, Denmark) for collagen IV and analyzed by light microscopy. Results. We observed mesothelial detachment from lamina propria, duplicated basement membrane and much thicker blood vessel walls in ESRD and PD patients, compared to healthy subjects. Differences in histological structure, emphasized with immunostaining, indicated pathological alterations of peritoneal tissue in the renal patients. Conclusions. Imunohistochemistry can be used in studying histological alterations of peritoneal tissue in ESRD and PD patients. This method may indicate possible problems in filtration and secretion processes in this tissue.

Introduction. Incontinentia pigmenti (IP) is a rare complex X-linked genodermatosis in which skin changes are combined with anomalies of other organs. Mutations of the NEMO gene localized on chromosome Xq28 are responsible for IP. Clinical manifestations of IP according to evolution and prognosis can be considered as skin changes and dental, eye and central nervous system changes. Objective. The aim of our study was to investigate type and frequency of ocular features in Serbian population. Methods. We investigated the total of 9 families with 22 subjects, 20 females and 2 males, at the Institute of Dermatovenerology, Clinical Centre of Serbia, in the period from 1989 to 2009. Our subjects were diagnosed clinically by a dermatologist and the diagnosis confirmed by cutaneous histopathology and ultrastructural analysis. The pedigrees, karyotype analyses, routine laboratory findings, additional specialized clinical examinations were done for all subjects. Results. Among 22 IP patients from our study, different ophthalmological anomalies were observed in 16% of subjects. In female subjects, all of them with clinical characteristics of IP, we observed the following anomalies: retinal detachment, microphthalmia, cataract, strabismus and nystagmus. Conclusion. Compared to available literature data, our percentage of IP patients with anomalies was lower. It may be due to differences in examined populations or due to the fact that the patients in our study were firstly admitted to the Institute of Dermatology. Ophthalmological findings may be often considered as very severe anomalies in IP. It is very important to detect IP as early as possible, medically help and monitor these patients.

Introduction. Incontinentia pigmenti (IP) is an X-linked genodermatosis in which skin changes are combined with dental, eye and central nervous system anomalies. Objective. The goal of the study was to analyze ocular findings, IP minor criteria in available literature concerning IP cases published until now. Methods. We have done meta-analysis of 1931 IP patients found in 302 references published until 2010. Comparison of data published for the 1906-1976 and 1976-2010 periods was made. The collected data were mainly frequencies of ocular anomalies. Chi-square test was used to compare observed frequencies with their expectations. Results. Of total number of IP patients, 1,227 were ophthalmologically investigated. In 449 such patients 972 eye anomalies were registered, 2.16 anomalies per patient. Proportion of ophthalmologically investigated IP patients in the period 1906-1975 (70%) was higher than corresponding proportion (60%) for the period 1976-2010. For 1906-2010 period 36.5% IP patients with eye anomalies were diagnosed. The number of amaurotic eyes per patient did not significantly differ for the two periods (p=0.50; >0.05). The total number of eye anomalies per patient significantly differed for the same periods (p=0.00005;

Background. Incontinentia pigmenti (IP) is a rare, complex, X-linked genodermatosis in which skin changes are combined with defects of other organs. It appears almost exclusively in females and is usually lethal in men. It is estimated that according to the available reported cases, there have been approximately 900-1 200 affected individuals, out of which 60 males. The aim of the study was to report two additional individual male cases with IP. Case reports. We discovered two male patients with IP according to standard IP diagnostic criteria. The diagnosis was made by a dermatologist and confirmed by cutaneous histopathology and ultrastructural analysis. The pedigrees, karyotype analyses and routine laboratory findings were made. Two male probands were the only ones with IP in their families, with no history of miscarriages. Both probands had normal karyotype. In one proband, acrocentric chromosomes of the group D had tendency of forming associations. Histopathological and ultrastructural skin analyses revealed findings typical for IP. Conclusion. The detection of each male case is very valuable because of their rarity. Application of the standard diagnostic criteria is necessary for comparison and epidemiological analysis. Monitoring such probands allows a better determination of how genetic transmission occurs, and is important because of the different degrees of severity of IP.

The aim of the study was to investigate the morphology of mesothelial cells of the peritoneum of patients with terminal renal failure (TRF), taken by the biopsy immediately before the onset of peritoneal dialysis (PD), and to compare it with the findings in patients with PD. The samples were prepared in the way standard for light microscopy and transmission electron microscopy. In patients with TRF intracytoplasmatic inclusions could be observed, unusual protrusions of mesothelial apical surfaces, deformation of mesothelial cells and their detachment from the basal membrane, as well as the dilatated cisternae of granulated endoplasmatic reticulum with filamentous structures in some of them. In patients on PD cytoplasmic protrusions of different shapes and contents were observed at the surface of mesothelial cells, multiplication of basal membrane, occurrence of young forms of mesothelial cells as well as the detachment of those cells from the basal lamina.

Abstract The objective of this study was to present a systematic review of the central nervous system (CNS) types of anomalies and to consider the possibility to include CNS anomalies in Incontinentia pigmenti (IP) criteria. The analyzed literature data from 1,393 IP cases were from the period 1993–2012. CNS anomalies were diagnosed for 30.44% of the investigated IP patients. The total number of CNS types of anomalies per patient was 1.62. In the present study there was no significantly higher number of anomalies per patient in females than males. The most frequent CNS types of anomalies were seizures, motor impairment, mental retardation, and microcephaly. The most frequently registered CNS lesions found using brain imaging methods were brain infarcts or necrosis, brain atrophies, and corpus callosum lesions. IKBKG exon 4–10 deletion was present in 86.00% of genetically confirmed IP patients. The frequency of CNS anomalies, similar to the frequency of retinal anomalies in IP patients, concurrent with their severity, supports their recognition in the list of IP minor criteria.

Objectives: Incontinentia pigmenti (IP) is an X-linked genodermatosis caused by a mutation of the IKBKG gene. The objective of this study was to present a systematic review of the dental and oral types of anomalies, to determine the total number and sex distribution of the anomalies, and to analyze possible therapies. Materials and methods: We analyzed the literature data from 1,286 IP cases from the period 1993-2010. Results: Dental and/or oral anomalies were diagnosed for 54.38% of the investigated IP patients. Most of the anomaly types were dental, and the most frequent of these were dental shape anomalies, hypodontia, and delayed dentition. The most frequent oral anomaly types were cleft palate and high arched palate. IKBKG exon 4-10 deletion was present in 86.36% of genetically confirmed IP patients. Conclusions: According to the frequency, dental and/or oral anomalies represent the most frequent and important IP minor criteria. The most frequent mutation was IKBKG exon 4-10 deletion. The majority of dental anomalies and some of the oral anomalies could be corrected. Clinical relevance: Because of the presence of cleft palate and high arched palate in IP patients, these two anomalies may be considered as diagnostic IP minor criteria as well. [ABSTRACT FROM AUTHOR]

One of interesting aspects in dermatology is the fact that skin may reflect the presence of anomalies in other organs and tissues. One such example is incontinentia pigmenti (IP), a rare, complex, X-linked genodermatosis. Clinical manifestations of IP according to evolution and prognosis can be considered as skin, as well as dental, eye, and central nervous system, changes. We have investigated a total of nine families with 25 subjects, 23 females and 2 males. In 12 female and 2 male subjects, all of them with clinical characteristics of IP, we observed the following abnormalities: teeth-shape anomalies (coni- or peg-like teeth), the presence of numerous cariotic teeth, early dental loss, delayed eruption, partial anodontia, and gothic palate. To our knowledge, this is the first time that the presence of gothic palate in patients with IP has been documented. As we found out, in two female subjects and one male subject, in which nonrandomed X inactivation did not occur, gothic palate could be supposed as characteristic of IP. [ABSTRACT FROM AUTHOR]

Masno tkivo je specijalizovano vezivno tkivo koje se ispoljava u dva oblika: belo (unilokulamo) i braon (multilokulamo) masno tkivo. Osnovna uloga belog masnog tkiva je skladištenje energije, dok je mrkog masnog tkiva termogeneza. Uz dva jasno izdvojena perioda rasta masnog tkiva, prvog koji se odvija tokom intrauterinog razvoja do 18. meseca života i drugog koji se javlja tokom puberteta, masno tkivo poseduje značajan potencijal za uvećanje volumena tokom života i razvoja gojaznosti. Tokom poslednjih godina utvrđeno je da i odrasle osobe poseduju aktivno braon masno tkivo, koje ima veliki kapacitet za uklanjanje lipida iz cirkulacije, termogenezu i značajan utrošak energije. Nedavno otkriće irisina, miokina koji se oslobađa iz skeletnih mišićnih ćelija tokom fizičke aktivnosti i putem cirkulacije dospeva do masnog tkiva u kome indukuje diferencijaciju braon masnih ćelija, pruža mogućnost za iznalaženje novih modaliteta u terapiji gojaznosti. [ABSTRACT FROM AUTHOR]

Abstract: In the previous study of the rat frontal cortex slices oxygen consumption (QO2), polarographically determined using the biological oxygen monitor, a moderate respiratory depressant action of midazolam ex vivo (1.0mg/kg) has been observed. Antagonist of the benzodiazepine binding site, flumazenil, blocked the effect of the agonist. However, midazolam–γ-aminobutyric acid (GABA) interactions pointed to the possibility that a part of midazolam action is independent of the classical GABA potentiation. To test this presumption, GABAA receptor antagonists bicuculline and picrotoxin were administered. Both blockers antagonized the QO2 reducing effect of the combination of per se effective doses of midazolam (1.0mg/kg) and GABA (5×10−4 mol/l), as well as of GABA (5×10−4 mol/l) itself. However, neither effects of midazolam (1.0mg/kg) on its own, nor those of midazolam in presence of the physiological, per se ineffective, concentration of GABA (10−6 mol/l), were susceptible to antagonism. These results show that ex vivo influence of midazolam on cerebral metabolic activity should be partly ascribed to some of its cellular mechanisms probably associated to the GABA modulation, but distinct from the standard GABA-potentiating effects of benzodiazepines. [Copyright &y& Elsevier]