Leg length and bristle density, both necessary for water surface locomotion, are genetically correlated in water striders.

Access to hitherto unexploited ecological opportunities is associated with phenotypic evolution and often results in significant lineage diversification. Yet our understanding of the mechanisms underlying such adaptive traits remains limited. Water striders have been able to exploit the water-air interface, primarily facilitated by changes in the density of hydrophobic bristles and a significant increase in leg length. These two traits are functionally correlated and are both necessary for generating efficient locomotion on the water surface. Whether bristle density and leg length have any cellular or developmental genetic mechanisms in common is unknown. Here, we combine comparative genomics and transcriptomics with functional RNA interference assays to examine the developmental genetic and cellular mechanisms underlying the patterning of the bristles and the legs in Gerris buenoi and Mesovelia mulsanti, two species of water striders. We found that two duplication events in the genes beadex and taxi led to a functional expansion of the paralogs, which affected bristle density and leg length. We also identified genes for which no function in bristle development has been previously described in other insects. Interestingly, most of these genes play a dual role in regulating bristle development and leg length. In addition, these genes play a role in regulating cell division. This result suggests that cell division may be a common mechanism through which these genes can simultaneously regulate leg length and bristle density. We propose that pleiotropy, through which gene function affects the development of multiple traits, may play a prominent role in facilitating access to unexploited ecological opportunities and species diversification.

Novel 1,3,4-Oxadiazole Derivatives of Pyrrolo[3,4-d]pyridazinone Exert Antinociceptive Activity in the Tail-Flick and Formalin Test in Rodents and Reveal Reduced Gastrotoxicity.

Despite the availability of the current drug arsenal for pain management, there is still a clinical need to identify new, more effective, and safer analgesics. Based on our earlier study, newly synthesized 1,3,4-oxadiazole derivatives of pyrrolo[3,4-d]pyridazinone, especially 10b and 13b, seem to be promising as potential analgesics. The current study was designed to investigate whether novel derivatives attenuate nociceptive response in animals subjected to thermal or chemical noxious stimulus, and to compare this effect to reference drugs. The antinociceptive effect of novel compounds was studied using the tail-flick and formalin test. Pretreatment with novel compounds at all studied doses increased the latency time in the tail-flick test and decreased the licking time during the early phase of the formalin test. New derivatives given at the medium and high doses also reduced the late phase of the formalin test. The achieved results indicate that new derivatives dose-dependently attenuate nociceptive response in both models of pain and exert a lack of gastrotoxicity. Both studied compounds act more efficiently than indomethacin, but not morphine. Compound 13b at the high dose exerts the greatest antinociceptive effect. It may be due to the reduction of nociceptor sensitization via prostaglandin E2 and myeloperoxidase levels decrease.

The influence of chemical structure on thermal properties and surface morphology of polyurethane materials.

The surface morphology and thermal properties of polyurethanes can be correlated to their chemical composition. The hydrophilicity, surface morphology, and thermal properties of polyurethanes (differed in soft segments and in linear/cross-linked structure) were investigated. The influence of poly([R,S]-3-hydroxybutyrate) presence in soft segments and blending of polyurethane with polylactide on surface topography were also estimated. The linear polyurethanes (partially crystalline) had the granular surface, whereas the surface of cross-linked polyurethanes (almost amorphous) was smooth. Round aggregates of polylactide un-uniformly distributed in matrix of polyurethane were clearly visible. It was concluded that some modification of soft segment (by mixing of poly([R,S]-3-hydroxybutyrate) with different polydiols and polytriol) and blending of polyurethanes with small amount of polylactide influence on crystallinity and surface topography of obtained polyurethanes.

Degradability of cross-linked polyurethanes based on synthetic polyhydroxybutyrate and modified with polylactide.

In many areas of application of conventional non-degradable cross-linked polyurethanes (PUR), there is a need for their degradation under the influence of specific environmental factors. It is practiced by incorporation of sensitive to degradation compounds (usually of natural origin) into the polyurethane structure, or by mixing them with polyurethanes. Cross-linked polyurethanes (with 10 and 30%wt amount of synthetic poly([R,S]-3-hydroxybutyrate) (R,S-PHB) in soft segments) and their physical blends with poly([d,l]-lactide) (PDLLA) were investigated and then degraded under hydrolytic (phosphate buffer solution) and oxidative (CoCl2/H2O2) conditions. The rate of degradation was monitored by changes of samples mass, morphology of surface and their thermal properties. Despite the small weight losses of samples, the changes of thermal properties of polymers and topography of their surface indicated that they were susceptible to gradual degradation under oxidative and hydrolytic conditions. Blends of PDLLA and polyurethane with 30 wt% of R,S-PHB in soft segments and PUR/PDLLA blends absorbed more water and degraded faster than polyurethane with low amount of R,S-PHB.

Susceptibility to Degradation in Soil of Branched Polyesterurethane Blends with Polylactide and Starch.

A very important method of reducing the amount of polymer waste in the environment is the introduction to the market of polymers susceptible to degradation under the influence of environmental factors. This paper presents the results of testing the susceptibility to degradation in soil of branched polyesterurethane (PUR) based on poly([R,S]-3-hydroxybutyrate) (R,S-PHB), modified with poly([D,L]-lactide) (PLA) and starch (St). Weight losses of samples and changes in surface morphology (SEM, OM and contact angle system) with simultaneously only slight changes in molecular weight (GPC), chemical structure (FTIR and 1HNMR) and thermal properties (DSC) indicate that these materials are subject to enzymatic degradation caused by the presence of microorganisms in the soil. Chemical modification of branched polyesterurethanes with R,S-PHB and their physical blending with small amounts of PLA and St resulted in a slow but progressive degradation of the samples.

Ovocystatin Induced Changes in Expression of Alzheimer's Disease Relevant Proteins in APP/PS1 Transgenic Mice.

Background: Ovocystatin is marked by structural and biological similarities to human cystatin C, which plays an important role in the course of neurodegenerative diseases. Recently, it has been shown that ovocystatin might prevent aging-related cognitive impairment in rats and reduce memory decline in an APP/PS1 mice model. Thus, this study aimed to assess the effect of ovocystatin on histopathological changes in APP/PS1 mice. Materials and methods: Ovocystatin was administered intraperitoneally for four weeks (40 µg/mouse) to 35-weeks-old transgenic (AD, n = 14) and wild type (NCAR, n = 15) mice (stock B6C3-Tg(APPswe, PSEN1dE9)85Dbo/Mmjax). A histopathological evaluation comprised antibodies directed against ß-amyloid (1:400, SIG-39320-1000, Covance) and Tau (1:4000, AHB0042, Invitrogen). Three regions of the hippocampus­ the dentate gyrus (DG) and the cornu ammonis (CA1 and CA3)­were analyzed by immunohistochemistry in each animal. All differences are expressed as percentage relative to the control group. Results: The main results showed that the percentage of immunoreactive area of ß-amyloid, tau protein deposits in APP/PS1+ovCYS was decreased in DG, CA1, and CA3 regions compared with the APP/PS1 control, respectively (p < 0.05). Conclusions: Ovocystatin caused significant changes in the expression pattern of all investigated proteins in hippocampal tissues both in APP/PS1 and NCAR mice.

Degradability of Polyurethanes and Their Blends with Polylactide, Chitosan and Starch.

One of the methods of making traditional polymers more environmentally friendly is to modify them with natural materials or their biodegradable, synthetic equivalents. It was assumed that blends with polylactide (PLA), polysaccharides: chitosan (Ch) and starch (St) of branched polyurethane (PUR) based on synthetic poly([R,S]-3-hydroxybutyrate) (R,S-PHB) would degrade faster in the processes of hydrolysis and oxidation than pure PUR. For the sake of simplicity in the publication, all three modifiers: commercial PLA, Ch created by chemical modification of chitin and St are called bioadditives. The samples were incubated in a hydrolytic and oxidizing environment for 36 weeks and 11 weeks, respectively. The degradation process was assessed by observation of the chemical structure as well as the change in the mass of the samples, their molecular weight, surface morphology and thermal properties. It was found that the PUR samples with the highest amount of R,S-PHB and the lowest amount of polycaprolactone triol (PCLtriol) were degraded the most. Moreover, blending with St had the greatest impact on the susceptibility to degradation of PUR. However, the rate of weight loss of the samples was low, and after 36 weeks of incubation in the hydrolytic solution, it did not exceed 7% by weight. The weight loss of Ch and PLA blends was even smaller. However, a significant reduction in molecular weight, changes in morphology and changes in thermal properties indicated that the degradation of the samples should occur quickly after this time. Therefore, when using these polyurethanes and their blends, it should be taken into account that they should decompose slowly in their initial life. In summary, this process can be modified by changing the amount of R,S-PHB, the degree of cross-linking, and the type and amount of second blend component added (bioadditives).

Long-Term Administration of Abacavir and Etravirine Impairs Semen Quality and Alters Redox System and Bone Metabolism in Growing Male Wistar Rats.

Highly active antiretroviral therapy (HAART) is used in HIV-infected patients. Alongside the prolongation of patients' life, adverse side effects associated with long-term therapy are becoming an increasing problem. Therefore, optimizing of HAART is extremely important. The study is aimed at evaluating the toxicity of abacavir and etravirine in monotherapy on the reproductive system, liver, kidneys, and bones in young, sexually mature, male rats. Thirty-six 8-week-old male Wistar rats randomized into three 12-animal groups received either normal saline (control), abacavir 60 mg/kg (AB group), or etravirine 40 mg/kg (ET group) once daily for 16 weeks. Semen morphology, oxide-redox state parameters (MDA, SOD, catalase, GPx, glutathione, GSH/GSSG ratio) in tissue homogenates (testes, liver, kidneys), and serum samples were studied. In bones, microcomputed tomography and a four-point bending test were performed. Total sperm count, sperm concentration, motility, and sperm morphology did not differ significantly in AB or ET groups compared to the control. In the flow cytometry of semen, an increased percentage of cells with denatured DNA was noticed for both tested drugs. However, no significant changes of oxide-redox state in testicular homogenates were found, except of increased SOD activity in the AB-receiving group. Additionally, ET significantly altered catalase and GPx in the liver and SOD activity in kidneys. Abacavir decreased catalase in the liver and GSH levels in kidneys. AB caused significant changes to bone microarchitecture (bone volume fraction, trabecular number, connectivity density, total porosity) and increased Young's modulus. Etravirine had a greater impact on macrometric parameters of bones (tibial index, mid-tibial diameter, femur length). After 4 weeks in the ET group, a lower 1,25-dihydroxyvitamin D3 serum concentration was found. The results showed that abacavir and etravirine disturb oxidative stress. An increase in the percentage of sperms with chromatin damage suggests decreased fertility in rats receiving the studied drugs. Both drugs affected bone formation in growing rats. Additionally, etravirine disturbed vitamin D metabolism.

Predicted Studies of Branched and Cross-Linked Polyurethanes Based on Polyhydroxybutyrate with Polycaprolactone Triol in Soft Segments.

The number of cross-links in the non-linear polyurethane structure is the basic factor affecting its properties. Selected properties of aliphatic polyurethanes with soft segments made of different amounts of polycaprolactonetriol, polycaprolactonediol and synthetic, telechelic poly([R,S]-3-hydroxybutyrate) were determined. On the basis of changes in polyurethane properties, the correlation between these properties and the construction of soft segments was found. The structure of polyurethanes, their morphology, hydrophilicity, thermal and mechanical properties were examined. These properties were changed linearly up to 15% content of polycaprolactonetriol in soft segments. A further increase in the amount of triol causes that these properties are mainly determined by the high number of cross-links.

Cornelian Cherry Iridoid-Polyphenolic Extract Improves Mucosal Epithelial Barrier Integrity in Rat Experimental Colitis and Exerts Antimicrobial and Antiadhesive Activities In Vitro.

BACKGROUND AND AIMS: Inflammatory bowel disease pharmacotherapy, despite substantial progress, is still not satisfactory for both patients and clinicians. In view of the chronic and relapsing disease course and not always effective treatment with adverse effects, attempts to search for new, more efficient, and safer substances are essential and reasonable. This study was designed to elucidate the impact of cornelian cherry iridoid-polyphenolic extract (CE) and loganic acid (LA) on adherent-invasive E. coli growth and adhesion in vitro and to assess the effect of pretreatment with CE or LA on the course of intestinal inflammation in rat experimental colitis compared with sulfasalazine. METHODS: Antibacterial and antiadhesive activities of CE and LA were assessed using microdilution, Int407 cell adherence, and yeast agglutination assays. The colitis model was induced by 2,4,6-trinitrobenzenesulfonic acid. Studied substances were administered intragastrically for 16 days prior to colitis induction. Body weight loss; colon index; histological injuries; IL-23, IL-17, TNF-α, and chemerin levels; and STAT3, Muc2, and TFF3 mRNA expression were evaluated. RESULTS: Only CE exerted antimicrobial and antiadhesive activities in vitro and alleviated colonic symptoms. CE coadministrated with sulfasalazine was more effective than single compounds in reversing increased concentrations of TNF-α, IL-17, and chemerin and decreased Muc2 mRNA expression. CONCLUSIONS: CE exerted a protective effect against experimental colitis via impaired mucosal epithelial barrier restoration and intestinal inflammatory response attenuation and given concomitantly with sulfasalazine counteracted colitis in a more effective way than sulfasalazine alone, which indicates their synergistic interaction. The beneficial effect of CE may also be due to its bacteriostatic and antiadhesive activities.

Morphology and Physicochemical Properties of Branched Polyurethane/Biopolymer Blends.

The aim of this study is the analyze the structure of branched polyurethanes based on synthetic poly([R,S]-3-hydroxybutyrate) and their blends with biopolymers and montmorillonite. The properties which would predict the potential susceptibility of these materials to degradation are also estimated. Fourier-transform infrared spectroscopy with attenuated total reflection analysis shows that poly([d,l]-lactide) is on the surfaces of polyurethanes, whereas chitosan and starch are included inside the blend network. Atomic force microscopy images have shown that the surfaces of investigated samples are heterogenous with the formation of spherulites in case of pure polyurethanes. The presence of biopolymers in the blend reduced the crystallinity of polyurethanes. Thermal stability of blends of polyurethanes with poly([d,l]-lactide) and polysaccharides decreased in comparison to pure polyurethanes. Although the tensile strength is reduced after the blending of polyurethanes with biopolymers, the elongation at break increased, especially in the case of polyurethane/poly([d,l]-lactide) blends. The presence of polysaccharides in the obtained blends caused the significant reduction of contact angle after one minute from water drop immersion. This hydrophilizing effect is the highest when montmorillonite has been incorporated into the chitosan blend. The estimated properties of the obtained materials suggest their potential sensitivity on environmental conditions.

Beneficial effect of ovocystatin on the cognitive decline in APP/PS1 transgenic mice.

PURPOSE: Cystatin C plays an important role in the course of neurodegenerative diseases and has a beneficial effect through inhibiting cysteine proteases and amyloid-ß aggregation. It also induces proliferation and autophagy. Cystatin isolated from chicken egg white, called ovocystatin, has been widely used in the medical and pharmaceutical research due to its structural and biological similarities to human cystatin C. The aim of this study was to assess the effect of administering ovocystatin on the development of dementia-specific cognitive deficits in APP/PS1 transgenic mice. MATERIALS/METHODS: The study was conducted on transgenic B6C3-Tg(APPswe,PSEN1dE9)85Dbo/Mmjax mice. Ovocystatin was administered to four-month-old transgenic (AD) and wild type (NCAR) mice in drinking water for 24 weeks (at a dose of 40 and 4 µg/ mouse). The locomotor activity and cognitive functions were determined using an actimeter and the Morris water maze test, respectively. RESULTS: The results of the study indicate that ovocystatin has a beneficial effect on the cognitive functions in APP/PS1 transgenic mice. The strongest effects of ovocystatin were found in the group of AD mice, where ovocystatin was administered in drinking water at a dose of 40 µg/mouse (p < 0.05). Mice from the AD group swam statistically significantly further in the target zone during the trial in the Morris water maze compared to the AD (vehiculum) group (p < 0.05). CONCLUSIONS: The obtained results encourage further research into the protective effect, which may be used as an adjuvant in the treatment of deteriorating cognitive functions.

Branched Polyurethanes Based on Synthetic Polyhydroxybutyrate with Tunable Structure and Properties.

Branched, aliphatic polyurethanes (PURs) were synthesized and compared to linear analogues. The influence of polycaprolactonetriol and synthetic poly([R,S]-3-hydroxybutyrate) (R,S-PHB) in soft segments on structure, thermal and sorptive properties of PURs was determined. Using FTIR and Raman spectroscopies it was found that increasing the R,S-PHB amount in the structure of branched PURs reduced a tendency of urethane groups to hydrogen bonding. Melting enthalpies (on DSC thermograms) of both soft and hard segments of linear PURs were higher than branched PURs, suggesting that linear PURs were more crystalline. Oil sorption by samples of linear and branched PURs, containing only polycaprolactone chains in soft segments, was higher than in the case of samples with R,S-PHB in their structure. Branched PUR without R,S-PHB absorbed the highest amount of oil. Introducing R,S-PHB into the PUR structure increased water sorption. Thus, by operating the number of branching and the amount of poly([R,S]-3-hydroxybutyrate) in soft segments thermal and sorptive properties of aliphatic PURs could be controlled.

Pharmacodynamic and pharmacokinetic interactions between simvastatin and diazepam in rats.

BACKGROUND: Statins and benzodiazepines are widely used drugs, especially in ischemic heart disease, where exacerbation caused by anxiety can even lead to cardiac death. There have not been any reports of statin drug interaction with anxiolytics so far, but it is possible that these drugs interact with each other. We examined the effect of chronic oral administration of simvastatin on the anxiolytic activity and pharmacokinetics of diazepam in rats. METHODS: Studies were conducted on male Wistar Han rats treated with simvastatin (2.5, 5, 10, 20mg/kg) for 4-6 weeks, and/or diazepam (2.5, 5, 10mg/kg) administered once on the day of the study. Evaluation of potential pharmacodynamic interaction was based on the behavioral tests: elevated plus maze (EPM) test and the Vogel conflict test (VCT). The assessment of the potential pharmacokinetic interaction was based on measurements of concentrations of diazepam and its metabolites in the blood of animals. RESULTS: Diazepam 5 and 10mg/kg given together with simvastatin 10 and 20mg/kg showed no anxiolytic effect in the EPM test. In the VCT diazepam combinations with simvastatin did not produce any anxiolytic effect either, with an exception of the co-administration of diazepam 10mg/kg and simvastatin 10mg/kg. Simvastatin (20mg/kg) significantly reduced the area under curve (AUC) of diazepam by 51.6% and temazepam by 54.6%. CONCLUSIONS: Abolition of diazepam anxiolytic effect during concomitant use of simvastatin is probably caused by diminished bioavailability of diazepam, although pharmacodynamic interaction between these drugs cannot be excluded.

Effects of cannabinoids on the anxiety-like response in mice.

Several pieces of anatomical, biochemical and pharmacological evidence indicate that the endocannabinoid system via CB1 receptors is implicated in the control of emotional behavior. However, previous studies have reported unclear and contradictory results concerning the role of cannabinoids in anxiety. The aim of the present study was to examine the influence of the cannabinoid agonist WIN 55,212-2 (1 and 5 mg/kg), the CB1 antagonist AM 281 (1, 2 and 4 mg/kg), the inhibitor of anandamide hydrolysis AACOCF3 (1 and 4 mg/kg) and the inhibitor of anandamide transporter AM404 (1 and 4 mg/kg) on the anxiety-like response in mice in the light/dark box test. WIN 55,212-2 (5 mg/kg) induced the anxiogenic-like effect accompanied by motor inhibition, AACOCF3 (4 mg/kg) induced the selective anxiolytic-like effect, whereas AM404 and AM281 were without effect. Pretreatment with AM281 (2 mg/kg) blocked the anxiogenic-like and sedative responses induced by WIN 55, 212-2, as well as the anxiolytic-like effect of AACOCF3. These results support the hypothesis that the endocannabinoid system is involved in the regulation of anxiety-like behavior, and also suggest that the inhibitors of anandamide hydrolysis might be potential anxiolytic drugs.

The effect of am 251, a cannabinoid CB1 receptor antagonist, on food intake in rats.

The anorectic effect of AM 251 (N-(piperidin-1-yl)-5-(4-iodophenyl)-1-(2,4-di-chlorophenyl)-4-methyl-1H-pyrazole-3-carboxamide), a CB1 receptor antagonist, was studied in rats. AM 251 (0.5-2.0 mg/kg i.p.) significantly and dose-dependently reduced food intake in both free-feeding and food-deprived rats. The obtained results support the anorectic activity of CB1 receptors antagonists.

Antidepressant--like properties of ACEA (arachidonyl-2-chloroethylamide), the selective agonist of CB1 receptors.

The antidepressant effect of ACEA (arachidonyl-2-chloroethylamide), a selective agonist of CB1 receptors, and its interaction with fluoxetine were studied in mice. ACEA (1.0 and 2.0 mg/kg i.p.) reduced the immobility time in the forced swimming test and attenuated the head - twitch response to L-5-HTP. The concomitant administration of ACEA (1.0 mg/kg i.p.) and fluoxetine (20 mg/kg i.p.) resulted in the strongest shortening of immobility time, significant in comparison with both ACEA and fluoxetine given alone. The obtained results indicate that ACEA may have antidepressant efficacy and shows a synergistic effect when given with fluoxetine in the forced swimming test.

Influence of nifedipine, nitrendipine and verapamil at low concentration on antipyrine metabolism examined by extracorporeal rat liver perfusion.

An increase in calcium ion concentration in the cytoplasm due to the influence of various toxic agents causes disturbances in the structure and function of hepatocytes, leading to their damage and even death. Calcium ions enter the cell mostly through calcium channels, therefore, it has been suggested that calcium channel inhibitors (CCI) could protect hepatocytes from the action of toxic substances. The present study investigated the effect of the selected CCI (nifedipine, nitrendipine and verapamil) on liver function, measured by the efficiency of oxidation reaction, in this case by determination of the rate of antipyrine metabolism. The experiment was carried out using the method of extracorporeal liver perfusion (ELP). None of the studied CCI applied at a concentration of 50 micromol/l increased the rate of antipyrine metabolism over the whole period of ELP. However, supplementation of perfusion fluid with nifedipine, nitrendipine or verapamil at a concentration of 20 micromol/l considerably improved metabolic liver efficiency during the second hour of perfusion, i.e. at the time, when large number of hepatocytes started to perish, which could indicate protective action of the tested CCI. However, the CCI-induced acceleration of antipyrine metabolism was not a result of their influence on calcium channels, since these drugs block calcium channels, when given at the concentrations as high as 100-400 micromol/l. Moreover, it seems that facilitation of antipyrine metabolism during ELP was not due to their action on microsomal enzymes because CCI were administered at very low concentrations, besides, they are metabolic inhibitors, and not inducers. The present experiment suggests that low concentrations of CCI can exert hepatoprotective effect. However, confirmation of this conclusion requires further studies using other experimental methods.