In the present study, we have investigated the role of antimalarial drug halofantrine (HF) in inducing the sterile protection against challenges with sporozoites of the live infectious Plasmodium yoelii (Killick-Kendrick, 1967) in Swiss mice malaria model. We observed that during the first to third sequential sporozoite inoculation cycles, blood-stage patency remains the same in the control and chemoprophylaxis under HF drug cover (CPS-HF) groups. However, a delayed blood-stage infection was observed during the fourth and fifth sporozoite challenges and complete sterile protection was produced following the sixth sporozoite challenge in CPS-HF mice. We also noticed a steady decline in liver stage parasite load after 3th to 6th sporozoite challenge cycle in CPS-HF mice. CPS-HF immunisation results in a significant up-regulation of pro-inflammatory cytokines (IFN-γ, TNF-α, IL-12 and iNOS) and down-regulation of anti-inflammatory cytokines (IL-10 and TGF-β) mRNA expression in hepatic mononuclear cells (HMNC) and spleen cells in the immunised CPS-HF mice (after 6th sporozoite challenge) compared to control. Overall, our study suggests that the repetitive sporozoite inoculation under HF drug treatment develops a strong immune response that confers protection against subsequent challenges with sporozoites of P. yoelii.
Perinatal hypoxia is still one of the greatest threats to the
newborn child, even in developed countries. However, there is
a lack of works which summarize up-to-date information about
that huge topic. Our review covers a broader spectrum of recent
results from studies on mechanisms leading to hypoxia-induced
injury. It also resumes possible primary causes and observed
behavioral outcomes of perinatal hypoxia. In this review, we
recognize two types of hypoxia, according to the localization of
its primary cause: environmental and placental. Later we analyze
possible pathways of prenatal hypoxia-induced injury including
gene expression changes, glutaminergic excitatory damage (and
a role of NMDA receptors in it), oxidative stress with ROS and
RNS production, inflammation and apoptosis. Moreover, we focus
on the impact of these pathophysiological changes on the
structure and development of the brain, especially on its regions:
corpus striatum and hippocampus. These brain changes of the
offspring lead to impairments in their postnatal growth and
sensorimotor development, and in their motor functions, activity,
emotionality and learning ability in adulthood. Later we compare
various animal models used to investigate the impact of prenatal
and postnatal injury (hypoxic, ischemic or combinatory) on living
organisms, and show their advantages and limitations.
The healthy development of the fetus depends on the exact course of pregnancy and delivery. Therefore, prenatal hypoxia remains between the greatest threats to the developing fetus. Our study aimed to assess the impact of prenatal hypoxia on postnatal development and behavior of the rats, whose mothers were exposed to hypoxia (10.5 % O2) during a critical period of brain development on GD20 for 12 h. This prenatal insult resulted in a delay of sensorimotor development of hypoxic pups compared to the control group. Hypoxic pups also had lowered postnatal weight which in males persisted up to adulthood. In adulthood, hypoxic males showed anxiety-like behavior in the OF, higher sucrose preference, and lower levels of grimace scale (reflecting the degree of negative emotions) in the immobilization chamber compared to the control group. Moreover, hypoxic animals showed hyperactivity in EPM and LD tests, and hypoxic females had reduced sociability compared to the control group. In conclusion, our results indicate a possible relationship between prenatal hypoxia and changes in sociability, activity, and impaired emotion regulation in ADHD, ASD, or anxiety disorders. The fact that changes in observed parameters are manifested mostly in males confirms that male sex is more sensitive to prenatal insults.
The Gram-negative, obligate intracellular tick-transmitted pathogen Anaplasma phagocytophilum can cause acute febrile diseases in humans and domestic animals. The expansion of the tick Ixodes ricinus (Linnaeus, 1758) in northern Europe due to climate change is of serious concern for animal and human health. The aim of the present study was to investigate the impact of A. phagocytophilum infection in moose Alces alces (Linnaeus) calves by evaluating the carcass weights of infected and non-infected animals and examining animal tissues samples for co-infections with either species of Babesia Starcovici, 1893 or bacteria of the genus Bartonella. The carcasses of 68 free-ranging moose calves were weighed by hunters during the hunting seasons from 2014 to 2017 in two regions in southern Norway and spleen samples were collected. Anaplasma phagocytophilum was detected in moose sampled from locations infected with ticks with a prevalence of 82% (n = 46). The carcass weights of A. phagocytophilum-infected calves (n = 46) and non-infected (n = 22) calves were compared. Although the average weight of infected calves (45.6 kg) was lower than that of non-infected calves (46.5 kg), the difference was not statistically significant. Three different variants of the bacterium 16S rRNA gene were identified. The average weight of animals infected with variant I was 49.9 kg, whereas that of animals infected with variant III was 42.0 kg, but the difference was not statistically significant (p = 0.077). Co-infections of A. phagocytophilum with Bartonella spp. or with Babesia spp. were found in 20 and two calves, respectively. A triple infection was found in two calves. Sequence analysis of the 18S rRNA gene of Babesia-positive samples revealed the presence of Babesia cf. odocoilei (Emerson et Wright, 1970). Strains of Bartonella closely related to Bartonella bovis (Bermond, Boulouis, Heller, Laere, Monteil, Chomel, Sander, Dehio et Piemont, 2002) were identified based on phylogenetic analysis of the gltA and rpoB genes. The loss of body mass in moose calves in the tick-infected site was probably influenced by multiple factors.
Animals, including human beings, tend to respond more strongly to stimuli that are associated with the highest relative rewards. This applies not only to food rewards but also to reproductive success. In the present review article this issue is discussed for insects in connection with intersexual communication and flower-visiting behaviour. Implications of the preference for supernormal visual releasing stimuli are examined from a sensory and evolutionary perspective, including a consideration of the choice of potential mates and recognition of the most rewarding flowers., Karl Kral., and Obsahuje bibliografii
We aimed to assess the importance of anthropogenic roosts for bats hibernating in the Roztocze National Park (south-east Poland), based on data collected from 2009 to 2021. We recorded 310 bats from nine species hibernating in 27 artificial underground roosts (root cellars and basements of buildings). The most abundant and constantly recorded species were Plecotus auritus (60.2%), Barbastella barbastellus (20.6%) and Myotis nattereri (14.2%), while the remaining species can be considered of secondary importance; Plecotus austriacus (1.3%), Myotis myotis (1.9%), Myotis bechsteinii (1.3%), M. daubentonii (0.3%), Myotis mystacinus sensu lato (0.3%) and Eptesicus serotinus (1.3%). An estimate of the Shannon diversity index gave a mean H = 0.947 (SD = 0.247, range 0.377-1.352), while the Buzas and Gibson´s evenness index gave values of E = 0.695 (SD = 0.125, range 0.551-0.940). The Shannon index was positively correlated with the number of recorded bats and varied substantially among years.
An increase in the renal resistive index (RRI) in patients with essential hypertension (EH) predicts deterioration in renal function. In patients with EH, changes in hemodynamic parameters significantly affect the RRI. This study aimed to define changes in Ambulatory Blood Pressure Monitoring (ABPM) parameters that are significantly associated with a change in RRI in patients with EH. We evaluated ABPM and the RRI in 96 patients with EH without organ extrarenal changes at baseline and after two years of follow-up. The relationships between changes in ABPM parameters and the RRI over the period were evaluated. After two years of follow-up, the increase in RRI was consequential. Simultaneously, 24-h systolic blood pressure increased significantly and 24-h diastolic blood pressure decreased. In the whole group and in the group with calculated cystatin C clearance (eGFRcyst) ≥90 ml/min/1.73 m2 , the change in RRI significantly negatively correlated with the change in the ratio of 24-h diastolic to systolic blood pressure (D/S ratio), but also with the change in 24-h pulse blood pressure. However, in patients with eGFRcyst˂90 ml/min/1.73 m2 , only the change in the 24-h D/S ratio significantly correlated with the change in RRI. Based on the backward stepwise regression analysis, the change in RRI was significantly dependent only on the change in 24-h D/S ratio and not on the change in 24-h pulse pressure. A change in the ratio of diastolic to systolic pressure better reflects a change in RRI than a change in pulse pressure.
An evaluation of possible interactions with enzymes of drug metabolism (cytochromes P450, CYP) is an important part of studies on safety and, in general, on the properties of any drug or biologically active compound. The article is focused on the preliminary metabolic study of selected 2,6,9-trisubstituted purine kinase inhibitors with significant anticancer activities which we have developed. The compounds BP-21 and BP-117 represent strong CDK inhibitors and the compound BPA-302 was developed as selective FLT3-ITD kinase inhibitor. Here, emphasis is placed on interactions of these compounds with the nine most important forms of CYP to evaluate the possibility of inhibition of these enzymes. The possibility of their inhibitory effect was studied in vitro on selected human liver microsomal CYP enzymes. The most affected enzyme was CYP2C19. Its activity dropped to 22 % of its original value by BPA-302, to 13 % by BP-21 and to 6 % by BP-117 at the highest concentration tested (250 µmol·l-1 ). The results suggest that the metabolism of concomitantly administered drugs should not be significantly affected at lower doses. Molecular docking of BPA-302 indicated that it can bind to active site of both CYP2C19 and CYP2D6 enzymes above the heme cofactor corroborating the experimental data.
Nickel is a ubiquitous environmental pollutant, which has various effects on reproductive endocrinology. In this study, human adrenocortical carcinoma (NCI-H295R) cell line was used as an in vitro biological model to study the effect of nickel chloride (NiCl2) on the viability and steroidogenesis. The cells were exposed to different concentrations (3.90; 7.80; 15.60; 31.20; 62.50; 125; 250 and 500 μM) of NiCl2 and compared with control group (culture medium without NiCl2). The cell viability was measured by the metabolic activity assay. Production of sexual steroid hormones was quantified by enzyme linked immunosorbent assay. Following 48 h culture of the cells in the presence of NiCl2 a dose-dependent depletion of progesterone release was observed even at the lower concentrations. In fact, lower levels of progesterone were detected in groups with higher doses (≥125 μM) of NiCl2 (P<0.01), which also elicited cytotoxic action. A more prominent decrease in testosterone production (P<0.01) was also noted in comparison to that of progesterone. On the other hand, the release of 17β-estradiol was substantially increased at low concentrations (3.90 to 62.50 μM) of NiCl2. The cell viability remained relatively unaltered up to 125 μM (P>0.05) and slightly decreased from 250 μM of NiCl2 (P<0.05). Our results indicate endocrine disruptive effect of NiCl2 on the release of progesterone and testosterone in the NCI-H295R cell line. Although no detrimental effect of NiCl2 (≤62.50 μM) could be found on 17β-estradiol production, its toxicity may reflect at other points of the steroidogenic pathway., Norbert Lukac, Zsolt Forgacs, Hana Duranova, Tomas Jambor, Jirina Zemanova, Peter Massanyi, Barbara Tombarkiewicz, Shubhadeep Roychoudhury, Zuzana Knazicka., and Obsahuje bibliografii
In order to clear airways and lungs defensive reflexes are
provoked rather by the dynamic phase of mechanical stimulus. It
is speculated that provocation of defensive response depends not
only on stimulus duration but also on stimulus velocity. Fourteen
adult rabbits were anaesthetized and tracheotomized. Mechanical
stimulus was provoked by a mechanical probe introduced
through the tracheotomy and rotated by a small electrical motor
using a rotational velocity of 40 rpm/s and 20 rpm/s. Threshold,
incidence and intensity of cough reflex (CR) were analyzed for
each animal. Statistical comparisons between two velocities were
performed using Friedman nonparametric test for repeated
measurements. Results are median (25-75 %). The threshold of
CR was significantly increased (p=0.005) from 350 ms (300-500
ms) to 550 ms (350-1150 ms) and the incidence of cough reflex
was significantly reduced (p=0.002) from 50 % (19-50 %) to
0 % (0-25 %) when the rotational velocity of the mechanical
probe was reduced by half. The findings of this study are of
interest as they show that protective reflex cough, an important
mechanism that allows clearing airways even during sleep or
anesthesia, is tuned by mechanical stimulus velocity.