Estradiol treatment and precopulatory behavior in ovariectomized female rats

Female rats of Wistar strain were injected SC, starting at Day 5 after ovariectomy, with estradiol dipropionate (ED) at weekly intervals. Forty-eight hours after each injection they were subjected to standardized mating tests. A 6 μg ED dose showed to be insufficient to maintain estrous behavior. Both precopulatory and lordosis behavior disappeared in the course of eight weeks. On the other hand, the behavioral effectiveness of 10 and 30 μg ED increased with the number of injected doses. Under these circumstances, estradiol proved to be sufficient to induce not only full copulatory readiness but also all the degree of precopulatory behavior of pattern (Presenting, Hopping ending in Presenting, and Darting ending in Presenting). Although there are large individual differences in behavioral effectiveness of ED, the estradiol thresholds for inducing Presenting, Hopping, and Darting were found to increase in the given order. However, prolonged (up to Week 12) treatment with 30 μg ED resulted in the disappearance all estrous behaviors. This decline of estradiol effectiveness was reversed by increasing the estradiol dose to 100 μg.     

Limited agreement between the interfacial tension and differential capacity data for the polarised water|1,2-dichloroethane interface

Quasi-elastic laser light scattering and impedance measurements at the water|1,2-dichloroethane interface are used to evaluate the interfacial tension and the differential capacity, respectively, as a function of the interfacial potential difference. Over the range of the potential differences around the zero-charge potential difference, the surface charge density obtained by integration of the capacity agrees well with that obtained by derivation of the interfacial tension. However, the ratio of these two charges starts to deviate significantly from unity close to the potential window limits, where the faradaic current associated with the transfer of the supporting electrolyte ions becomes more pronounced, and where the capacity shows a remarkable enhancement. These results corroborate our previous experimental observations and conclusions, which threw doubts on the previous interpretation of the effect of electrolytes on the differential capacity in terms of the ion association, ion interpenetration, or specific ion adsorption. In the potential range where the capacity data can be reliably obtained, an effect of the nature of the organic electrolyte on both the interfacial tension and the differential capacity is observed, which can be ascribed to the change in the thickness of the inner (compact) layer due to a difference in the radius of the ions present.     

Age‐related changes in the tooth–bone interface area of acrodont dentition in the chameleon

Chameleon teeth develop as individual structures at a distance from the developing jaw bone during the pre‐hatching period and also partially during the post‐hatching period. However, in the adult, all teeth are fused together and tightly attached to the jaw bone by mineralized attachment tissue to form one functional unit. Tooth to bone as well as tooth to tooth attachments are so firm that if injury to the oral cavity occurs, several neighbouring teeth and pieces of jaw can be broken off. We analysed age‐related changes in chameleon acrodont dentition, where ankylosis represents a physiological condition, whereas in mammals, ankylosis only occurs in a pathological context. The changes in hard‐tissue morphology and mineral composition leading to this fusion were analysed. For this purpose, the lower jaws of chameleons were investigated using X‐ray micro‐computed tomography, laser‐induced breakdown spectroscopy and microprobe analysis. For a long time, the dental pulp cavity remained connected with neighbouring teeth and also to the underlying bone marrow cavity. Then, a progressive filling of the dental pulp cavity by a mineralized matrix occurred, and a complex network of non‐mineralized channels remained. The size of these unmineralized channels progressively decreased until they completely disappeared, and the dental pulp cavity was filled by a mineralized matrix over time. Moreover, the distribution of calcium, phosphorus and magnesium showed distinct patterns in the different regions of the tooth–bone interface, with a significant progression of mineralization in dentin as well as in the supporting bone. In conclusion, tooth–bone fusion in chameleons results from an enhanced production of mineralized tissue during post‐hatching development. Uncovering the developmental processes underlying these outcomes and performing comparative studies is necessary to better understand physiological ankylosis; for that purpose, the chameleon can serve as a useful model species.     

5-Substituted 2-amino-4,6-dihydroxypyrimidines and 2-amino-4,6-dichloropyrimidines: synthesis and inhibitory effects on immune-activated nitric oxide production

A series of 5-substituted 2-amino-4,6-dihydroxypyrimidines were prepared by a modified condensation of the corresponding monosubstituted malonic acid diesters with guanidine in an excess of sodium ethoxide. The optimized procedure using Vilsmeier–Haack–Arnold reagent, followed by immediate deprotection of the (dimethylamino)methylene protecting groups, has been developed to convert the 2-amino-4,6-dihydroxypyrimidine analogs to novel 5-substituted 2-amino-4,6-dichloropyrimidines in high yields. Pilot screening for biological properties of the prepared compounds was done in mouse peritoneal cells using the in vitro nitric oxide (NO) assay. Irrespective of the substituent at the 5 position, 2-amino-4,6-dichloropyrimidines inhibited immune-activated NO production. The most effective was 5-fluoro-2-amino-4,6-dichloropyrimidine with an IC ₅₀ of 2 µM (higher activity than the most potent reference compound) while the IC ₅₀s of other derivatives were within the range of 9–36 µM. The 2-amino-4,6-dihydroxypyrimidine counterparts were devoid of any NO-inhibitory activity. The compounds had no suppressive effects on the viability of cells. The Mechanism of action remains to be elucidated.     

The effect of brisk walking on postural stability,bone mineral density,body weight and composition in women over 50 years with a sedentary occupation: a randomized controlled trial

Background

To assess the effect of brisk walking on postural stability, bone mineral density (BMD) and body composition in women over 50 years of age with a sedentary occupation.

Methods

A 10-week walking intervention based on self-regulated brisk walking (BW) to or from work of 30–35 min at least 5 times per week. The research included a total of 104 women (58 women in intervention group). The mean center of pressure (COP) velocity in medial-lateral and anterior-posterior directions, mean total COP velocity with eyes open and closed, BMD of the distal forearm and the calcaneus, body weight, fat mass, and lean body mass were assessed.

Results

The BW intervention was completed by 76 % of participants. A significant effect (time?×?group interaction) was confirmed only in the mean COP velocity in the anterior-posterior direction with eyes closed (F?=?7.41, P?=?0.008). The effect of BW was not confirmed in BMD, body weight, or body composition. The results indicate that the effect of the intervention is influenced by baseline body mass index in body weight, fat mass and visceral adipose tissue.

Conclusions

BW prevents the deterioration of postural stability with eyes closed, which can have a direct effect on reducing the risk of falls under worse spatial orientation and visibility. The presented intervention model is insufficient for weight loss, changes in BMD, or body composition, and its effect should be assessed during a longer period of time.

Trial registration

German Clinical Trials Register DRKS00007638, registered March 10, 2015 (retrospectively registered).

     

Efficacy and safety of peripheral blood stem cell collection in elderly donors; does age interfere?

Elderly patients with hematological malignancies are often reliant on allogeneic transplantations. Older family relatives are increasingly involved in utilization as PBSC donors. We analyzed the mobilization results from 103 donors of age ≥55 years in comparison with 121 younger donors of age <55 years. The median CD34+ count in peripheral blood on day +5 of the mobilization was higher in younger than in older donor group (72.0 vs. 37.0 cells/μL, P < 0.0001). Linear regression showed a negative correlation between the age and CD34+ count in peripheral blood (P < 0.0001) and apheresis product (P < 0.0001). Based on multivariate analysis, the amount of circulating CD34+ cells appeared to be negatively influenced by age (P < 0.001) and positively by the preapheresis WBC count (P < 0.001). The precollection CD34+ (P < 0.0001), PLT (P = 0.0144) counts, and age (P = 0.0392) were confirmed as independent factors determining the collection yield. The side effects of G-CSF administration were similar in both the groups. Apheresis complications were more frequently recorded in elderly donors (29 vs. 15%, P = 0.0096). Higher age represents a risk factor for poorer mobilization results. A requirement for more than one apheresis in older donors occurs more frequently to obtain the adequate amount of CD34+ cells. Mobilization and collection procedures are associated with acceptable risks and complication rates in elderly donors.     

Anti-inflammatory active gold(I) complexes involving 6-substituted-purine derivatives

The gold(I) complexes of the general formula [Au(L(n))(PPh(3))]·xH(2)O (1-8; n = 1-8 and x = 0-1.5), where L(n) stands for a deprotonated form of the benzyl-substituted derivatives of 6-benzylaminopurine, were prepared, thoroughly characterized (elemental analyses, FT-IR, Raman and multinuclear NMR spectroscopy, ESI+ mass spectrometry, conductivity, DFT calculations), and studied for their in vitro cytotoxicity and in vitro and in vivo anti-inflammatory effects on LPS-activated macrophages (derived from THP-1 cell line) and using the carrageenan-induced hind paw edema model on rats. The obtained results indicate that the representative complexes (1, 3, 6) exhibit a strong ability to reduce the production of pro-inflammatory cytokines TNF-α, IL-1β and HMGB1 without influence on the secretion of anti-inflammatory cytokine IL-1RA in the LPS-activated macrophages. The complexes also significantly influence the formation of edema, caused by the intraplantar application of polysaccharide λ-carrageenan to rats in vivo. All the tested complexes showed similar or better biological effects as compared with Auranofin, but contrary to Auranofin they were found to be less cytotoxic in vitro. The obtained results clearly indicate that the gold(I) complexes behave as very effective anti-inflammatory agents and could prove to be useful for the treatment of difficult to treat inflammatory diseases such as rheumatoid arthritis.     

Differential effects of acyclic nucleoside phosphonates on nitric oxide and cytokines in rat hepatocytes and macrophages

Acyclic nucleoside phosphonates (ANP) are virostatics effective against viruses like hepatitis B virus and human immunodeficiency virus. Our previous reports indicated immunomodulatory activities of ANP in mouse and human innate immune cells. Recently, evidence has increased that hepatocytes may play an active role in immune regulation of the liver homeostasis or injury. In this study we investigated possible immunomodulatory effects of ANP on rat hepatocytes and macrophages. Nitric oxide (NO) production and secretion of cytokines (IL-1α, IL-1β, IL-2, IL-4, IL-6, IL-10, IL-13, IL-18, IFN-γ, TNF-α and GM-CSF) were analyzed under in vitro conditions. Test compounds included: 9-[2-(phosphonomethoxy)ethyl]adenine (PMEA; adefovir); 9-[2-(phosphonomethoxy)ethyl]-2,6-diaminopurine (PMEDAP); (R)- and (S)-enantiomers of 9-[2-(phosphonomethoxy)propyl]adenine [(R)-PMPA; tenofovir] and [(S)-PMPA]; 9-[2-(phosphonomethoxy)propyl]-2,6-diaminopurine [(R)-PMPDAP] and [(S)-PMPDAP]. The group of test compounds also included their N(6)-substituted derivatives. Some of ANP which are able to induce NO production and cytokine secretion in cultured macrophages possess the same immunobiological activity in isolated hepatocytes. The extent of responses is in range of LPS/IFN-γ stimulation in both types of cells. The effects of active ANP on NO expression and cytokine secretion are dose- and time-dependent. Interestingly, the spectrum of detected cytokines induced by ANP is broader in hepatocytes. The results also confirm immunomodulatory effects of some ANP on rodent macrophages. Moreover, we demonstrate for the first time immunobiological reactivity of primary rat hepatocytes induced by exogenous ANP compounds. The potential of hepatocytes to synthesize cytokines can contribute to better understanding of liver immune function and can serve for pharmacological intervention in liver diseases.