Hemispheric infiltrative grade II gliomas in adults: association of residual tumour volume and extent of tumour resection with malignant transformation.

OBJECTIVES: Evaluation of the impact of surgical treatment on malignant transformation (MT) of adult supratentorial infiltrative grade II gliomas (G2G) in a series of chemotherapy and radiotherapy-naïve patients. BACKGROUND: Despite G2G are slow-growing tumours, they typically undergo MT with a subsequent fatal disease course. An extensive resection alone likely changes their biological behaviour and defers MT; however, this impact is not unequivocally confirmed. METHODS: Thirty-eight chemotherapy and radiotherapy-naïve adult patients operated from 2005 till 2014 for a G2G were investigated. Based on postoperative magnetic resonance imaging (MRI) and/or positron emission tomography follow-up (FU) scans, the patients were classified as "transformers" (15 patients in whom MT occurred during the FU-period) and "non-transformers" (23 patients). RESULTS: The follow-up period of "non-transformers" was longer (p <0.0001). After adjustment for known risk factors - age, male sex, astrocytoma histology, preoperative tumour volume, preoperative contrast enhancement and positive isocitrate dehydrogenase 1 gene mutation status - a larger log postoperative tumour volume (p=0.031) and a smaller extent of resection (p=0.0086) were associated with a shorter MT-free survival. CONCLUSION: In our series, less extensive resections were associated with a shorter time to MT. Our data support an adoption of techniques enabling extensive G2G resections, such as intraoperative imaging and awake resections, into everyday routine (Tab. 1, Fig. 2, Ref. 40).

Measurement of Urea in the Saliva of Healthy Mice - a Pilot Study.

Salivary urea is studied as a non-invasive alternative for screening and monitoring of renal diseases. Its high variability prevents a wider clinical use. Animal experiments are needed to identify factors affecting this marker. The aim of this study was to describe the inter-individual variability of salivary urea in healthy mice, establish reference intervals, and analyse the effects of sex, age and body weight. Plasma and saliva samples were obtained from 37 male and 41 female healthy adult CD1 mice aged 13-69 weeks (body weight 22-51 g). The reference interval for salivary urea in heathy mice based on our results is 2.7-8.4 mmol/l (CV = 23 %). Multivariate analysis did not show any significant effect of age, sex, or body weight. In addition, salivary urea did not correlate with its plasma concentrations. The high variability of the promising salivary marker of kidney function in healthy mice requires further research before its use to diagnose or monitor renal failure in animal models of kidney diseases. Other potential confounders should be analysed, including intra-individual and pre-analytical variability. In addition, a normalization factor such as total salivary proteins or salivation rate is likely needed.

The role of sex hormones and social determinants in assessment of facial attractiveness.

OBJECTIVES: The current study is focused on assessing the factors of attractiveness of opposite-sex individuals based on evaluating photographs of their faces. BACKGROUND: When assessing the attractiveness, factors of both, the assessed individual and the assessor play a role. The relationship of the preference for partners based on their physical appearance with the markers of prenatal testosterone is not fully understood. METHODS: Sex hormone levels were measured in saliva, while age, social status, income and occupation were recorded. A total of 30 women and 35 men were enrolled. RESULTS: The identified factors determining the attractiveness of menare their age and prenatal testosterone level (second-to-fourth digit ratio - 2D:4D). The attractiveness of men is more influenced by the factors of evaluating women, namely the rating assigned to the men positively correlates with age, 2D:4D, and salivary estradiol of the evaluating women. The attractiveness of women correlated negatively with age and positively with prenatal exposure to androgens (2D:4D).The women with lower estradiol were rated higher by men who themselves had low estradiol levels. The attractiveness did not correlate with current testosterone. CONCLUSION: This study contributes to the knowledge on the role of sex hormones in human sexuality and partner choice. Further studies should include genetic factors of testosterone metabolism. (Tab. 4, Ref. 23).

Does the 2nd and 4th digit ratio reflect prenatal androgen exposure?

OBJECTIVES:  The aim of our study was to describe the effect of prenatal testosterone exposure on 2D:4D in both sexes, and to determine whether this effect is mediated via the androgen receptor. In addition, the sex differences in lengths of 2D, 4D, and 2D:4D ratio were analyzed. BACKGROUND:  Clinical studies suggest a negative correlation between prenatal testosterone exposure and ratio of the lengths of the second and fourth digits (2D:4D). However, less is known about the underlying molecular mechanisms. METHODS:  Pregnant rats were treated with olive oil, testosterone, flutamide or testosterone with flutamide daily from the fourteenth day of pregnancy until delivery. The finger lengths of adult offspring were measured using both, digital scanning of the paws and µCT analysis of the phalanges. RESULTS:  None of the aforementioned methods revealed any effect of testosterone on 2D:4D. µCT measurements showed that prenatal hyperandrogenism in both sexes leads to shorter 2D compared to controls. Moreover, the testosterone treatment in males resulted in the shortening of 4D when compared to controls. CONCLUSION:  Prenatal hyperandrogenism leads to shorter lengths of 2D and 4D; however, it does not affect 2D:4D ratio. Whether other steroid hormones and/or testosterone metabolites affect the 2D:4D ratio requires further investigation (Tab. 5, Fig. 3, Ref. 32).

Beneficial effects of live and dead Salmonella-based vector strain on the course of colitis in mice.

Dysbiosis of intestinal microbiota and hyperactive immune responses seem to be crucial for the uncontrolled inflammation in inflammatory bowel diseases (IBD). Modulation of the microbiome and immune stimulation of the intestinal epithelium were suggested as therapeutic approaches. In this study, live attenuated and dead bacterial cells of Salmonella Typhimurium SL7207 - a widely used bacterial vector for gene therapy were administered in DSS-induced colitis in mice. C57BL/6 mice were divided into four groups. The first group received pure water (CTRL). The other three groups received 2% dextran sulphate sodium (DSS) to induce colitis. Two DSS groups were treated with live attenuated (DSS live) or inactivated (DSS dead) Salmonella by gastric gavage. Intake of 2% DSS caused weight loss in all DSS groups compared to control mice with some improvement in DSS live group on the last day of the experiment. Significantly longer colon and improved stool consistency were reported in DSS live group, but not DSS dead group, when compared with DSS. Significant enlargement of spleens was observed only in DSS and DSS dead groups compared to control. Significant differences in stool consistency, colon length and spleen enlargement were observed between DSS live and DSS dead groups with beneficial effects of live bacteria. Interestingly, significant decrease in myeloperoxidase activity was detected in both, DSS live and DSS dead groups compared to the DSS group. On the basis of these results, progression of colitis seems to be beneficially influenced not only by live attenuated but to some extent also by inactivated Salmonella Typhimurium SL7207. Our results provide evidence that Salmonella-based gene therapy vectors are able to positively alter gut homeostasis during DSS-induced colitis. SIGNIFICANCE AND IMPACT OF THE STUDY: Restoration of gut homeostasis has a great importance in IBD. Here, we tested the nonspecific effect of the strain Salmonella Typhimurium SL7207 on the course of colitis to find out whether the potential effect would be mediated by activity of live bacterial cells or by bacterial structures that are also present in dead bacteria. Live bacterial therapy of colitis showed a beneficial effect on clinical signs as well as on macroscopic and inflammatory markers of colitis. On the other hand, therapy with dead bacteria showed inconsistent effects, negative in most clinical outcomes, positive especially in myeloperoxidase activity. Our data indicate that the beneficial effect of bacterial gene therapy vectors carrying therapeutic genes might be, at least partially, caused by the bacterial vector instead of the therapeutic gene.

Anthocyanin-Rich Diet in Chemically Induced Colitis in Mice.

The aetiology of inflammatory bowel diseases is unclear, but oxidative stress plays a key role in the pathogenesis. Anthocyanins--plant polyphenols--were shown to have antioxidant and anti-inflammatory properties. The aim of this study was to investigate the potential protective effects of anthocyanins on the oxidative status in mice with chemically induced colitis. Adult male mice were randomly divided into a control group drinking tap water and a colitis group drinking 1% dextran sulphate sodium solution. Animals had ad libitum access to a control wheat-based diet or food based on wheat producing anthocyanins. Bodyweight and stool consistency were monitored daily for 14 days. At the end of the experiment, colon length was measured and tissue samples were collected for the assessment of histology and oxidative status. Mice with colitis had lower body weight, higher stool score and shorter colon than control mice. Anthocyanins had neither an effect on stool consistency, nor on bodyweight loss and colon length. In the colon, liver and plasma, analysis of oxidative stress markers and antioxidant status revealed no significant differences between the groups. Food made from wheat producing anthocyanins did not protect mice from the consequences of chemically induced colitis. The measured biomarkers do not confirm the role of oxidative stress in this model of colitis. Further optimization of the anthocyanin-rich food might be needed before further experiments are conducted.

Reference values of skin autofluorescence as an estimation of tissue accumulation of advanced glycation end products in a general Slovak population.

AIMS: For decades, Slovakia has maintained a prominent place in mortality rates from cardiovascular diseases among European Union (EU-27) countries. Determination of skin autofluorescence serves as an estimate of tissue accumulation of advanced glycation end products--substances accumulating in tissues and body fluids that play a pathophysiological role in age-related diseases and their complications, such as diabetes. METHODS: In 1385 apparently healthy Slovakian subjects aged from a few days old to 77 years, skin autofluorescence was determined using an advanced glycation end product reader and compared with reference data from Dutch Caucasians. The impact of the weekly frequency of recreational physical exercise on skin autofluorescence was investigated in the adults, and the impact of feeding regimen in the infants. RESULTS: With the exception of 10- to 19-year-olds, Slovaks had lower skin autofluorescence values in comparison with the Dutch Caucasians. In healthy non-smokers, physical exercise for > 30 min/day performed ≥ 3 times/week was associated with lower skin autofluorescence levels. In infants, breastfeeding (advanced glycation end product-poor diet) was associated with lower skin autofluorescence levels in comparison with consumption of infant formulas (advanced glycation end product-rich diet). CONCLUSIONS: Reference ranges of skin autofluorescence in Slovak Caucasians, detailed for paediatric age groups, are provided. Our data show that, in healthy adults, regular physical exercise associates with lower skin autofluorescence. Infants fed or weaned from infant formulas (advanced glycation end product-rich diet) have higher skin autofluorescence than their breast milk-consuming counterparts. It is unclear why Slovaks have lower skin autofluorescence compared with a Dutch population with lower cardiovascular mortality rates. Reference data on skin autofluorescence from diverse populations are needed for the precise clinical interpretation of skin autofluorescence measurements.

Testosterone and estradiol are not affected in male and female patients with obstructive sleep apnea treated with continuous positive airway pressure.

BACKGROUND: Continuous positive airway pressure (CPAP) improves symptoms in patients with obstructive sleep apnea syndrome (OSAS). It is currently unclear, whether CPAP also alters endocrine parameters such as sex hormone levels. In a previous study, we have found no changes in sex hormones in patients with OSAS after one night with CPAP. AIM: The aim of this study was to prove long-term effects of CPAP on sex hormone concentrations in patients with OSAS. METHODS: Twenty-two women and 67 men with severe OSAS (respiratory distress index > 30/h) were enrolled in the study. Fasting blood venous samples were taken before CPAP therapy and after 1 and 6 months of CPAP treatment. Testosterone and estradiol were measured in all samples using commercially available ELISA kits. RESULTS: No effects of long-term CPAP treatment were found on testosterone or estradiol levels in OSAS patients of either gender. CONCLUSIONS: The results are in line with previous smaller studies. However, our study is larger and longer than previously published studies. In addition, this is the first study analyzing the effects of CPAP on testosterone and estradiol and in both genders. Positive effects of CPAP on sexual functions reported in other studies might, thus, be mediated by other than endocrine effects.

On the origin and diagnostic use of salivary RNA.

Saliva as a diagnostic fluid enables non-invasive sampling, which can be performed even by an untrained person. Saliva is, thus, particularly useful for large population screenings, for children, elderly and whenever repeated samplings are needed. Saliva is a plasma filtrate actively modified by the salivary glands. Saliva could replace some routine blood tests in the future. The sources of salivary RNA include oral epithelial cells and oral micro-organisms. Recent developments suggest that using known salivary RNA markers, it is possible to diagnose diseases such as oral carcinoma and other diseases will be added soon. Salivary RNA can be used to identify oral bacteria and to determine the expression of specific genes. On a systemic level, it provides information about the whole oral transcriptome and microbiome. Despite the small amount of salivary RNA, the issues with its isolation have been overcome. Saliva, thus, contains RNA of sufficient quality and quantity for sensitive and specific analyses. Salivary RNA can provide medically relevant information about oral microbiome, oral carcinoma, but also breast and pancreatic cancer and is, thus, a promising tool for future research and clinical diagnostics.

Short-term effects of continuous positive airway pressure on sex hormones in men and women with sleep apnoea syndrome.

Patients with sleep apnoea syndrome (SAS) suffer from symptoms of hypogonadism. Besides surgical interventions, in some cases, the standard care of SAS for most patients is continuous positive airway pressure (CPAP). Studies focusing on the long-term effects of CPAP on testosterone levels revealed conflicting results. None of the studies included female patients with SAS. The aim of our study was to analyse and compare sex hormone levels in saliva before and after a night without and with CPAP in women and men with SAS. The results were negative. One night with CPAP did not affect the dynamics of sex hormones, neither in men nor in women. Future studies should focus on long-term effects of CPAP in both genders.

Effect of exogenous testosterone on oxidative status of the testes in adult male rats.

The aim of this study was to investigate the testosterone-induced changes in the oxidative status of testes in adult male rats treated either with testosterone or after blockade of androgen receptors with cyproterone acetate. A total of 40 intact rats were divided into four groups: a control group receiving sterile oil, the testosterone group receiving testosterone isobutyras, the cyproterone group receiving cyproterone acetate and the combination group receiving both testosterone isobutyras and cyproterone acetate. Treatments were carried out for 2 days by intramuscular application. Parameters of oxidative stress and the expression levels of the steroidogenic acute regulatory protein (StAR) gene were measured in testes. Significantly increased TBARS and advanced glycation end products (AGEs) levels were found in the testosterone group when compared to the control group. The °1 ferric-reducing ability of the tissue and total antioxidative capacity were lower in the testosterone group in comparison with the control group. Gene expression analysis revealed significant downregulation of the StAR gene in the testes of rats in the testosterone and combination groups with respect to control animals. In conclusion, administration of exogenous testosterone influences the lipid peroxidation and carbonyl stress and decreases the antioxidant defence in the testes. These data might have implications for male fertility in humans.

Prevalence of mutations in thiopurine S-methyltransferase gene among Slovak IBD patients.

BACKGROUND: Thiopurine S-methyltransferase (TPMT) plays an important role in the metabolism of thiopurines. It has been suggested that TPMT genetic polymorphisms lead to dose-related hematopoietic toxicity. Since there are major ethnic differences in the prevalence of particular TPMT variants, it is important for each country to study their own prevalence in order to estimate the role of TPMT variants-related thiopurines toxicity in population suffering from particular inflammatory bowel disease (IBD). AIMS: The aim of this study was to determine the frequency of the four most common allelic variants of TPMT gene in the population of Slovak IBD patients. METHODS: TPMT genetic polymorphisms (TPMT*2, TPMT*3A, TPMT*3B, TPMT*3C) were amplified using PCR and consequently genotyped with genetic analyzer. The allele frequencies of particular allelic variants were calculated and compared with other Caucasian populations reported so far. RESULTS: Three hundred and thirty IBD patients were included; 196/132/2 cases of Crohn´s disease/ulcerative colitis/unclassified colitis; 180 (55 %) males. Ninety-three percent of patients were homozygous for wild-type TPMT variant. Heterozygous genotype of any of the studied polymorphisms was present in 6 % of patients while only one patient was homozygous for TPMT*3A allele (0.3 %). The most prevalent mutant allele was that of TPMT*3A (3.2 %). The distribution of most common allelic variants of TPMT gene among Slovak IBD patients was in accordance with previously reported prevalence in Caucasian populations. CONCLUSION: This study shows the prevalence of TPMT genetic polymorphisms in population of Slovak IBD patients. As in other Caucasian populations, the most common mutant allelic variant is that of TPMT*3A while the prevalence of homozygosity is relatively low (Tab. 3, Ref. 22).

The impact of thiopurine-S-methyltransferase genotype on the adverse drug reactions to azathioprine in patients with inflammatory bowel diseases.

BACKGROUND AND AIMS: The thiopurine drugs, azathioprine (AZA) and 6-mercaptopurine, are established in the treatment of inflammatory bowel diseases (IBD). Polymorphisms in thiopurine S-methyltransferase (TPMT) gene have been associated with adverse drug reactions (ADRs) to AZA. METHODS: The aim of this study was to evaluate TPMT polymorphisms and AZA-related toxicity in a Slovak cohort of 220 IBD patients treated with AZA. In every patient, the dose and duration of AZA therapy, concomitant 5-aminosalicylate (5-ASA) medication, frequency, type, time to onset, dose of ADR and concomitant 5-ASA at the onset of ADR were recorded. Each patient was also genotyped for the presence of variant TPMT alleles (*2,*3A,*3B,*3C). Frequency, type and circumstances of ADRs were compared according to TPMT status. RESULTS: Of the 220 patients, 205 (93.2 %) were wild-type (TPMT*1/*1), one (0.5%) carried a TPMT*1/*3C allele, 13 (5.9 %) carried TPMT *1/*3A allele and one was homozygous for TMPT *3A allele. No TPMT *2 mutation was found. The incidence of adverse drug reactions was 62/205 (30.2 %) in the wild-type group as compared to 13/15 (86.7 %) in the TPMT mutation group, p=2.10-5. Leukopenia (WBC< 3.0*10^9/L) occurred in 21/205 (10.2 %) patients with wild type TPMT versus 11/15 (73.3 %) patients with TPMT mutations, p=0.000001. There was no significant difference between TMPT groups in gastrointestinal or other ADRs. No impact of 5-ASA on the incidence and severity of AZA adverse drug reactions was observed. CONCLUSION: The incidence of leukopenia in TPMT mutant patients was significantly higher and more severe as compared to TPMT wild type patients. We observed no impact of concomitant 5-ASA therapy on AZA induced toxicity (Tab. 4, Fig. 2, Ref. 37).

Recombinant probiotic therapy in experimental colitis in mice.

Recently, high interest has been attracted to the research of inflammatory bowel diseases (IBD). Recombinant probiotic bacteria may represent an interesting way to influence the course of IBD. Their benefits include cheap and simple production and easy manipulation of the genetic material. Several gene therapy and probiotic approaches already showed promising results in the past. The aim of this study was to test the probiotic potential of IL-10-expressing Escherichia coli Nissle 1917 in a mouse model of IBD and to compare it with control bacterial strains. The dextran sulphate sodium (DSS) model of colitis was examined for this purpose. Animals received control probiotic bacteria or modified probiotics (expressing IL-10) via gastric gavage. Body weight, stool consistency, food and water consumption were monitored. At the end of the experiment, the parameters of inflammation, oxidative stress and carbonyl stress were analysed in the samples and statistical analysis was performed. We prepared an anti-inflammatory probiotic Escherichia coli strain that we designated Nissle 1917/pMEC-IL10 and proved its anti-inflammatory properties, which are similar to those of the control probiotic strains Nissle 1917 and Lactococcus lactis/pMEC-IL10 in vivo. The probiotic therapy was successful according to several parameters, including colon length, and oxidative and carbonyl stress. Bacterially produced IL-10 was detected in the plasma. The potential of bacterial anti-inflammatory therapy of IBD using modified probiotics was outlined. The results opened a way for upcoming studies using modified probiotics for therapy of systemic diseases.

Prevalence of mutations in thiopurine S-methyltransferase gene among Slovak IBD patients.

BACKGROUND: Thiopurine S-methyltransferase (TPMT) plays an important role in the metabolism of thiopurines. It has been suggested that TPMT genetic polymorphisms lead to dose-related hematopoetic toxicity. Since there are major ethnic differences in the prevalence of particular TPMT variants, it is important for each country to study their own prevalence in order to estimate the role of TPMT variants-related thiopurines toxicity in the particular inflammatory bowel disease (IBD) population. AIMS: The aim of this study was to determine the frequency of the four most common allelic variants of TPMT gene in the population of Slovak IBD patients. METHODS: TPMT genetic polymorphisms (TPMT*2, TPMT*3A, TPMT*3B, TPMT*3C) were amplified using PCR and consequently genotyped on genetic analyzer. The allele frequencies of particular allelic variants were calculated and compared with other Caucasian populations reported so far. RESULTS: Three hundred and thirty IBD patients were included; 196/132/2 Crohn´s disease/ulcerative colitis/unclassified colitis, 180 (55 %) males. Ninety-three percent of patients were homozygous for wild type TPMT variant. Heterozygous genotype of any of the studied polymorphisms was present in 6 % of patients, only one patient was homozygous for TPMT*3A allele (0.3 %). The most prevalent mutant allele was TPMT*3A (3.2 %). The distribution of the most common allelic variants of TPMT gene among Slovak IBD patients were in accordance with previously reported prevalence in Caucasian populations. CONCLUSION: This study shows the prevalence of TPMT genetic polymorphisms in the Slovak IBD patient`s population. As in other Caucasian populations, the most common mutant allelic variant is TPMT*3A, and the prevalence of homozygosity is relatively low (Tab. 3, Ref. 16).

Early dynamics of glial fibrillary acidic protein and extracellular DNA in plasma of mice after closed head traumatic brain injury.

BACKGROUND: Glial fibrillary acidic protein (GFAP) in plasma is an established biomarker of traumatic brain injury (TBI) in humans. Plasma extracellular DNA (ecDNA) is a very sensitive, although nonspecific marker of tissue damage including TBI. Whether plasma GFAP or ecDNA could be used as an early non-invasive biomarker in the mouse model of closed head injury is unknown. The aim of this paper was to describe the early dynamics of plasma GFAP and ecDNA in the animal model of closed head TBI. METHODS: Closed head TBI was induced using the weight-drop method in 40 adult CD1 mice and blood was collected in different time points (1, 2 or 3h) after TBI in different groups of mice. Plasma GFAP and ecDNA and ecDNA fragmentation from the experimental groups were compared to healthy controls. In the surviving mice, a static rods test was performed 30 days after TBI to assess the neurological outcome of TBI. RESULTS: Despite a trend of higher plasma GFAP after TBI the differences between the groups were not statistically significant. Plasma ecDNA was higher by 50% after 1h (P<0.05) and 2h (P<0.05) after TBI and was highly variable after 3h. Plasma ecDNA, but not GFAP, was partially predictive of the neurological impairment of the mice. CONCLUSION: In this study, we have described the early dynamics of plasma GFAP and ecDNA after TBI in mice. According to our results, ecDNA in plasma is a more sensitive early marker of TBI than GFAP. Analysis of tissue-specific ecDNA might improve its predictive value regarding the survival and neurobehavioral outcome.

Gene therapy for cancer: bacteria-mediated anti-angiogenesis therapy.

Several bacterial species have inherent ability to colonize solid tumors in vivo. However, their natural anti-tumor activity can be enhanced by genetic engineering that enables these bacteria express or transfer therapeutic molecules into target cells. In this review, we summarize latest research on cancer therapy using genetically modified bacteria with particular emphasis on blocking tumor angiogenesis. Despite recent progress, only a few recent studies on bacterial tumor therapy have focused on anti-angiogenesis. Bacteria-mediated anti-angiogenesis therapy for cancer, however, is an attractive approach given that solid tumors are often characterized by increased vascularization. Here, we discuss four different approaches for using modified bacteria as anti-cancer therapeutics--bactofection, DNA vaccination, alternative gene therapy and transkingdom RNA interference--with a specific focus on angiogenesis suppression. Critical areas and future directions for this field are also outlined.

Targeting angiogenesis for cancer (gene) therapy.

Suppression of development of new blood vessels in solid tumors provides a clear therapeutic benefit both in experimental animals and human patients. Molecules targeting multiple pathways with VEGF pathway being one of the best described are currently under consideration to reach use in clinical settings. Even though some success has been observed using traditional protein-based inhibitors, alternative strategies and new approaches to inhibit excessive tumor angiogenesis are being developed and tested. Gene therapy represents a powerful tool for therapeutic intervention to angiogenesis. Delivery of genes encoding endogenous angiogenesis inhibitors and decoy receptors for proangiogenic factors may bear an advantage over classic non-gene therapy in terms of specific targeting, cost-effectiveness and safety. Modern approaches focused on gene targeting such as RNA interference and microRNA will show the future direction in the field of angiogenesis inhibition for cancer treatment (Ref. 68).

The impact of serotonergic stimulation on reelin and glutamate decarboxylase gene expression in adult female rats.

BACKGROUND: Reelin plays an important role in the regulation of synaptic plasticity in adulthood. Administration of 5-metoxytryptamine (5MT), an agonist of serotonin receptors, during natal and neonatal periods results in decreased reelin expression. In adulthood, reelin is expressed by GABAergic neurons. OBJECTIVES: The purpose of this study was to reveal the effect of elevated serotonergic stimulation on the expression of reelin and glutamate decarboxylase (GAD1) in adulthood as well as on depressive behavior and spatial cognitive abilities in adult female rats. METHODS: Rats were injected with 5MT. A forced swimming test was used for evaluation of the depressive behavior and Morris water maze test was used for evaluation of spatial cognition. Brains were used for measuring the expression of reelin and GAD1. RESULTS: We found a significant decrease in reelin expression in the cerebellum and prefrontal cortex of 5MT-treated rats. GAD1 expression was decreased in the cerebellum of 5MT-treated rats. 5MT-treated rats reached a lower immobility score in the forced swimming test. The Morris water maze test did not reveal any significant differences. CONCLUSION: We have shown that administration of serotonin receptor agonist resulted in a decreased RELN and GAD1 expression in the cerebellum of adult female rats. We propose that this phenomenon might be relevant in the pathogenesis of autism (Fig. 3, Ref. 38). Full Text in free PDF www.bmj.sk.

Acute effect of cola and caffeine on locomotor activity in drosophila and rat.

Caffeine is well known for reducing fatigue and its effect on behavior is widely studied. Usually, caffeine is not ingested in its pure form but rather in sugar-sweetened beverages such as cola. Our aim was to compare the acute effect of cola and caffeine on locomotor activity. Rats and flies ingested cola or caffeine solution for 24 hours. The open field test revealed higher locomotor activity in cola groups for both flies and rats. Surprisingly, no differences have been observed between caffeineand control group. We conclude that caffeine itself does not explain the effect of cola on locomotor activity. Effect of cola cannot be generalized and interpreted for any caffeinated drink with other contents. Rather, the observed effect on locomotor activity may be caused by interaction of caffeine with other substances present in cola.