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We report herein anti-proliferation effects of 4-arylthiosemicarbazides, with a cyclopentane substitution at N1 position, on highly virulent RH strain of Toxoplasma gondii. Among them, the highest in vitro anti-Toxoplasma activity was found with the meta-iodo derivative. Further experiments demonstrated inhibitory effects of thiosemicarbazides on tyrosinase (Tyr) activity, and good correlation was found between percentage of Tyr inhibition and IC50Tg. To confirm the concept that thiosemicarbazides are able to disrupt tyrosine metabolism in Toxoplasma tachyzoites, the most potent Tyr inhibitors were tested for their efficacy of T. gondii growth inhibition. All of them significantly reduced the number of tachyzoites in the parasitophorous vacuoles (PVs) compared to untreated cells, as well as inhibited tachyzoites growth by impeding cell division. Collectively, these results indicate that compounds with the thiosemicarbazide scaffold are able to disrupt tyrosine metabolism in Toxoplasma tachyzoites by deregulation of their crucial enzyme tyrosine hydroxylase (TyrH).

Approximately one-third of the human population is infected with the intracellular cosmopolitan protozoan Toxoplasma gondii (Tg), and a specific treatment for this parasite is still needed. Additionally, the increasing resistance of Tg to drugs has become a challenge for numerous research centers. The high selectivity of a compound toward the protozoan, along with low cytotoxicity toward the host cells, form the basis for further research, which aims at determining the molecular targets of the active compounds. Thiosemicarbazide derivatives are biologically active organic compounds. Previous studies on the initial preselection of 58 new 4-arylthiosemicarbazide derivatives in terms of their anti-Tg activity and selectivity made it possible to select two promising derivatives for further research. One of the important amino acids involved in the proliferation of Tg and the formation of parasitophorous vacuoles is tyrosine, which is converted by two unique aromatic amino acid hydroxylases to levodopa. Enzymatic studies with two derivatives (R: para-nitro and meta-iodo) and recombinant aromatic amino acid hydroxylase (AAHs) obtained in the E. coli expression system were performed, and the results indicated that toxoplasmic AAHs are a molecular target for 4-arylthiosemicarbazide derivatives. Moreover, the drug affinity responsive target stability assay also confirmed that the selected compounds bind to AAHs. Additionally, the anti-inflammatory activity of these derivatives was tested using THP1-Blue™ NF-κB reporter cells due to the similarity of the thiosemicarbazide scaffold to thiosemicarbazone, both of which are known NF-κB pathway inhibitors.

Mycobacterium tuberculosis (Mtb) is an intracellular pathogenic bacterium and the causative agent of tuberculosis. This disease is one of the most ancient and deadliest bacterial infections, as it poses major health, social and economic challenges at a global level, primarily in low- and middle-income countries. The lack of an effective vaccine, the long and expensive drug therapy, and the rapid spread of drug-resistant strains of Mtb have led to the re-emergence of tuberculosis as a global pandemic. Here, we assessed the in vitro activity of new imidazole-thiosemicarbazide derivatives (ITDs) against Mtb infection and their effects on mycobacterial biofilm formation. Cytotoxicity studies of the new compounds in cell lines and human monocyte-derived macrophages (MDMs) were performed. The anti-Mtb activity of ITDs was evaluated by determining minimal inhibitory concentrations of resazurin, time-kill curves, bacterial intracellular growth and the effect on biofilm formation. Mutation frequency and whole-genome sequencing of mutants that were resistant to ITDs were performed. The antimycobacterial potential of ITDs with the ability to penetrate Mtb-infected human macrophages and significantly inhibit the intracellular growth of tubercle bacilli and suppress Mtb biofilm formation was observed.

Two distinct intracellular pathogens, namely Mycobacterium tuberculosis (Mtb) and Toxoplasma gondii (Tg), cause major public health problems worldwide. In addition, serious and challenging health problems of co-infections of Tg with Mtb have been recorded, especially in developing countries. Due to this fact, as well as the frequent cases of resistance to the current drugs, novel anti-infectious therapeutics, especially those with dual (anti-Tg and anti-Mtb) modes of action, are needed. To address this issue, we explored the anti-Tg potential of thiazolidinedione-based (TZD-based) hybrid molecules with proven anti-Mtb potency. Several TZD hybrids with pyridine-4-carbohydrazone (PCH) or thiosemicarbazone (TSC) structural scaffolds were more effective and more selective than sulfadiazine (SDZ) and trimethoprim (TRI). Furthermore, all of these molecules were more selective than pyrimethamine (PYR). Further studies for the most potent TZD-TSC hybrids 7, 8 and 10 and TZD-PCH hybrid molecule 2 proved that these compounds are non-cytotoxic, non-genotoxic and non-hemolytic. Moreover, they could cross the blood–brain barrier (BBB), which is a critical factor linked with ideal anti-Tg drug development. Finally, since a possible link between Tg infection and the risk of glioblastoma has recently been reported, the cytotoxic potential of TZD hybrids against human glioblastoma cells was also evaluated. TZD-PCH hybrid molecule 2 was found to be the most effective, with an IC50 of 19.36 ± 1.13 µg/mL against T98G cells.

The increasing resistance of Toxoplasma gondii to drugs and side effects of therapy indicate that specific treatment for these parasites is still needed. The 4-arylthiosemicarbazide derivatives seem to be a solution to this challenge because they have low cytotoxicity against host cells and high anti-T. gondii activity. The molecular mechanism for these compounds is related to the inhibition of tyrosine amino acids involved in the proliferation and parasitophorous vacuole formation. The pharmacokinetic analysis shows that 1-(4-Methylimidazol-5-oyl)-4-(4-nitrophenyl)thiosemicarbazide and 4-(3-Iodophenyl)-1-(4-methylimidazol-5-oyl)thiosemicarbazide administered intragastrically pass into the bloodstream and cross the blood-brain barrier, and the absorption of both compounds is first-order absorption. Toxicity analysis shows that our derivatives possess lower toxicity than the routinely used drugs trimethoprim, sulfadiazine and pyrimethamine, as was observed in the level of liver enzymes and creatinine. Both derivatives are highly potent antiparasitic agents against T. gondii, prolonged survival and cure parasite-infected mice. Additionally, significant reductions in cyst formation in the brain and heart were observed, but the highest decreases were noted in muscle and the level of bradyzoites was similar to these observed in mice treated with commercially used drugs. Collectively, the obtained results support the conclusion that both compounds are highly efficacious in a mouse model of acute and chronic toxoplasmosis.

As a very successful pathogen with outstanding adaptive properties, Mycobacterium tuberculosis (Mtb) has developed a plethora of sophisticated mechanisms to subvert host defenses and effectively enter and replicate in the harmful environment inside professional phagocytes, namely, macrophages. Here, we demonstrated the binding interaction of Mtb with a major human acute phase protein, namely, serum amyloid A (SAA1), and identified AtpA (Rv1308), ABC (Rv2477c), EspB (Rv3881c), TB 18.6 (Rv2140c), and ThiC (Rv0423c) membrane proteins as mycobacterial effectors responsible for the pathogen-host protein interplay. SAA1-opsonization of Mtb prior to the infection of human macrophages favored bacterial entry into target phagocytes accompanied by a substantial increase in the load of intracellularly multiplying and surviving bacteria. Furthermore, binding of human SAA1 by Mtb resulted in the up- or downregulation of the transcriptional response of tubercle bacilli. The most substantial changes were related to the increased expression level of the genes of two operons encoding mycobacterial transporter systems, namely, mmpL5/mmpS5 (rv0676c), and rv1217c, rv1218c. Therefore, we postulate that during infection, Mtb-SAA1 binding promotes the infection of host macrophages by tubercle bacilli and modulates the functional response of the pathogen.

Congenital and acquired toxoplasmosis caused by the food- and water-born parasite Toxoplasma gondii (T. gondii) is one of the most prevalent zoonotic infection of global importance. T. gondii is an obligate intracellular parasite with limited capacity for extracellular survival, thus a successful, efficient and robust host cell invasion process is crucial for its survival, proliferation and transmission. In this study, we screened a series of novel 1,3,4-thiadiazole-2-halophenylamines functionalized at the C5 position with the imidazole ring (1b–12b) for their effects on T. gondii host cell invasion and proliferation. To achieve this goal, these compounds were initially subjected to in vitro assays to assess their cytotoxicity on human fibroblasts and then antiparasitic efficacy. Results showed that all of them compare favorably to control drugs sulfadiazine and trimethoprim in terms of T. gondii growth inhibition (IC50) and selectivity toward the parasite, expressed as selectivity index (SI). Subsequently, the most potent of them with meta-fluoro 2b, meta-chloro 5b, meta-bromo 8b, meta-iodo 11b and para-iodo 12b substitution were tested for their efficacy in inhibition of tachyzoites invasion and subsequent proliferation by direct action on established intracellular infection. All the compounds significantly inhibited the parasite invasion and intracellular proliferation via direct action on both tachyzoites and parasitophorous vacuoles formation. The most effective was para-iodo derivative 12b that caused reduction in the percentage of infected host cells by 44% and number of tachyzoites per vacuole by 93% compared to non-treated host cells. Collectively, these studies indicate that 1,3,4-thiadiazoles 1b–12b, especially 12b with IC50 of 4.70 µg/mL and SI of 20.89, could be considered as early hit compounds for future design and synthesis of anti-Toxoplasma agents that effectively and selectively block the invasion and subsequent proliferation of T. gondii into host cells.

The aim of this study was to evaluate the immunogenic and immunoprotective activities and to determine the neuroprotective capacity of the tetravalent vaccine containing selected recombinant T. gondii antigens (ROP2 + ROP4 + SAG1 + MAG1) administered with safe adjuvants (MPL and alum) using male and female inbred mice. The tested antigenic combination provided partial protection against brain cyst formation, especially in males (reduction in cyst burden by 72%). The decrease in cyst burden was observed for the whole brain as well as for specified brain regions associated with natural defensive behaviors, emotion processing and integration of motor and sensory stimuli. The vaccine triggered a strong, specific immune response, regardless of sex, which was characterized by the antigen-specific in vitro synthesis of cytokines (IL-2, IFN-γ and IL-10) and in vivo production of systemic IgG1 and IgG2a immunoglobulins. Immunization prior to the parasite challenge seemed to influence T. gondii – associated behavioral and neurochemical changes, although the impact of vaccination strongly depended on sex and time post-infection. Interestingly, in the vaccinated and T. gondii infected mice there was a significant delay in the parasite-induced loss of aversion toward cat smell (cats are the definitive hosts of the parasite). The regained attraction toward feline scent in vaccinated males, observed during chronic parasite invasion, correlated with the increase in the dopamine metabolism.

Synthesis and investigation of anti-Toxoplasma gondii activity of novel thiazoles containing benzo [b]thiophene moiety are presented. Among the derivatives, compound 3k with adamantyl group shows exceptionally high potency against Me49 strain with IC50 (8.74 μM) value which is significantly lower than the activity of trimethoprim (IC50 39.23 μM). In addition, compounds 3a, 3b and 3k showed significant activity against RH strain (IC50 51.88–83.49 μM). The results of the cytotoxicity evaluation showed that Toxoplasma gondii growth was inhibited at non-cytotoxic concentrations for the mammalian L929 fibroblast (CC30 ∼ 880 μM). The most active compound 3k showed tyrosinase inhibition effect, with IC50 value of 328.5 μM. The binding energies calculated for compounds 3a-3e, 3k are strongly correlated with the experimentally determined values of tyrosinase inhibition activity. Moreover, the binding energies corresponding to the same ligands and calculated for both tyrosinase and tyrosine hydroxylase are also correlated with each other, suggesting that tyrosinase inhibitors may also have an inhibitory effect on tyrosine hydroxylase. Compounds 3j and 3k have also very strong antioxidant activity (IC50 15.9 and 15.5 μM), respectively, which is ten times higher than well-known antioxidant BHT.

Toxoplasmosis is one of the most common parasitic diseases worldwide and it poses a serious challenge regarding prevention, diagnosis and therapy. The commonly used diagnostic methods are mostly based on the detection of specific antibodies in sera. Since they are not always accurate enough and do not allow precise definition of the phase of the Toxoplasma gondii infection, there is an urgent need to find specific molecular markers of acute or chronic infection stages. This study provides a comparative assessment of recombinant ROP5 and ROP18 T. gondii proteins in the serodiagnosis of human toxoplasmosis. We found that both ROP5 and ROP18 proteins allowed the detection of specific IgM and IgG antibodies with a relatively low sensitivity; however, ROP18 IgM ELISA proved to be more sensitive than the SAG1 assay. This study also points to a relatively weak potential of the corresponding native ROP5 and ROP18 kinases in the generation of a strong antibody response in humans.

Twelve 4-benzoyl-1-dichlorobenzoylthiosemicarbazides have been tested as potential antibacterials. All the compounds had MICs between 0.49 and 15.63 µg/ml toward Micrococcus luteus, Bacillus cereus, Bacillus subtilis and Staphylococcus epidermidis indicating, in most cases, equipotent or even more effective action than cefuroxime. In order to clarify if the observed antibacterial effects are universal, further research were undertaken to test inhibitory potency of two most potent compounds 3 and 11 on clinical isolates of Staphylococcus aureus. Compound 11 inhibited the growth of methicillin-sensitive S. aureus (MSSA) at MICs of 1.95-7.81 µg/ml, methicillin-resistant S. aureus (MRSA) at MICs of 0.49-1.95 µg/ml and MDR-MRSA at MIC of 0.98 and 3.90 µg/ml, respectively. Finally, inhibitory efficacy of 3 and 11 on planktonic cells and biofilms formation in clinical isolates of S. aureus and Haemophilus parainfluenzae was tested. The majority of cells in biofilm populations of MSSA and MRSA were eradicated at low level of 3, with MBICs in the range of 7.82-15.63 µg/ml.

The protozoan Toxoplasma gondii, an obligate intracellular parasite, is an etiological agent of human and animal toxoplasmosis. Treatment regimens for T. gondii-infected patients have not essentially changed for years. The most common chemotherapeutics used in the therapy of symptomatic toxoplasmosis are a combination of pyrimethamine and sulfadiazine plus folinic acid or a combination of pyrimethamine with lincosamide or macrolide antibiotics. To protect a fetus from parasite transplacental transmission, therapy of pregnant women is usually based on spiramycin, which is quite safe for the organism, but not efficient in the treatment of infected children. Application of recommended drugs limits replication of T. gondii, however, it may be associated with numerous an severe adverse effects. Moreover, medicines have no impact on the tissue cysts of the parasite located predominantly in a brain and muscles. Thus, there is urgent need to develop new drugs and establish "gold standard" treatment. In this review classical treatment of toxoplasmosis as well as potential compounds active against T. gondii have been discussed. For two last decades studies on the development of new anti-T. gondii medications have been focused on both natural and novel synthetic compounds based on existing chemical scaffolds. They have revealed several promising drug candidates characterized by a high selectivity, the low IC50 (the half maximal inhibitory concentration) and low cytotoxicity towards host cells. These drugs are expected to replace or supplement current anti-T. gondii drug arsenal soon.

Toxoplasma gondii, a protozoan parasite, is capable of infecting a broad range of intermediate warm-blooded hosts including humans. The parasite undergoes sexual reproduction resulting in genetic variability only in the intestine of the definitive host (a member of the cat family). The parasite seems to be capable of altering the natural behavior of the host to favor its transmission in the environment. The aim of this study was to evaluate the number of parasite cysts formed in the hippocampus and amygdala of experimentally infected mice as these regions are involved in defense behaviors control and emotion processing, and to assess the influence of the infection on mice behavior. The obtained results revealed the presence of parasite cysts both in the hippocampus and the amygdala of infected mice; however, no clear region-dependent distribution was observed. Furthermore, infected mice showed significantly diminished exploratory activity described by climbing and rearing, smaller preference for the central, more exposed part of the OF arena and engaged in less grooming behavior compared to uninfected controls.

The aim of this study was to test the potential diagnostic usefulness of recombinant Toxoplasma gondii rhoptry antigens, ROP2 and ROP4, with respect to toxoplasmosis detection and infection phase distinction in laboratory mouce by determining specific serum IgM and IgG antibodies with the use of indirect ELISA technique. The mice antibody response to ROP antigens was significantly higher in the IgM than in the IgG class with the peak on the turn of acute and latent infection, whereas the response to recombinant SAG1 antigen, used as control, revealed preferential synthesis of IgG antibodies with the highest absorbance values measured during latent toxoplasmosis.

Toxoplasmosis is a one of the most world-wide spread zoonosis representing a very serious clinical and veterinary problem. In the presented study, we evaluated the protective efficacy of a combined recombinant ROP2 and ROP4 subunit vaccine in a chronic Toxoplasma gondii infection in mice. The recombinant ROP2 (rROP2) and ROP4 (rROP4) proteins were cloned and expressed in Escherichia coli and then used for the immunization of C3H/HeJ mice. Both antigens generated a strong systemic mixed Th1/Th2 response polarized towards IgG1 antibody isotype. In contrast to rROP2 stimulating only the specific IL-2 release, rROP4 and crude toxoplasma lysate antigen (TLA) used as a source of native forms of the parasite proteins induced significant proliferation of splenocytes and specific production of IFN-γ as well as IL-2, the Th1-type cytokines. Challenge of rROP2 and rROP4-vaccinated mice with cysts of low virulent T. gondii DX strain resulted in a partial protection effect with a significantly lower brain parasites load when compared with control animals. In the immunized group of mice the brain cysts number was reduced by nearly 46% as was determined in two independent experiments. These results suggest that, similar to ROP2, rhoptry protein ROP4 could be a very good candidate for future anti-T. gondii multicomponent vaccine based on the recombinant forms of different parasite proteins.

Toxoplasmosis is one of the most common parasitic infections worldwide. An effective vaccine against human and animal toxoplasmosis is still needed to control this parasitosis. The polymorphic rhoptry proteins, ROP5 and ROP18, secreted by Toxoplasma gondii during the invasion of the host cell have been recently considered as promising vaccine antigens, as they appear to be the major determinants of T. gondii virulence in mice. The goal of this study was to evaluate their immunogenic and immunoprotective activity after their administration (separately or both recombinant proteins together) with the poly I:C as an adjuvant. Immunization of BALB/c and C3H/HeOuJ mice generated both cellular and humoral specific immune responses with some predominance of IgG1 antibodies. The spleen cells derived from vaccinated animals reacted to the parasite's native antigens. Furthermore, the immunization led to a partial protection against acute and chronic toxoplasmosis. These findings confirm the previous assumptions about ROP5 and ROP18 antigens as valuable components of a subunit vaccine against toxoplasmosis.

In the present article, we describe the inhibitory potency of nine thiosemicarbazide derivatives against bacterial type IIA topoisomerases, their antibacterial profile and molecular modelling evaluation. We found that one of the tested compounds, compound 7, significantly inhibits activity of Staphylococcus aureus DNA gyrase with an IC50 below 15 μM. Besides, this compound displays antibacterial activity on reference Staphylococuss spp. and Enterococcus faecalis strains as well as clinical S. aureus isolates at non-cytotoxic concentrations in mammalian cells with MIC values ranging from 16 to 32 μg/mL thereby indicating, in some cases, equipotent or even more effective action than standard drugs such as vancomycin, ampicillin and nitrofurantoin. The computational studies showed that both molecular geometry and the electron density distribution have a great impact on antibacterial activity of thiosemicarbazide derivatives.

Using murine chronic toxoplasmosis as an experimental model, we examined the utility of immunoenzymatic methods in recognizing reinfection in chronically infected individuals. Primary infection with avirulent Toxoplasma gondii DX strain (genotype II) induced strong immunity protecting the mice from mortality after inoculation with LD(100) of virulent BK strain (genotype I) and triggered highly expressed antibody production, within one new isotype detected by comparative immunoblots. The parasites multiplying at the site of reinfection were of BK origin as found by RAPD-PCR. The results revealed that the immunoblot assay seems to be a useful and reliable method for the monitoring of specific antibody profile in chronically infected individuals. In our opinion ELISA combined with immunoblot could enable the recognition of reinfection cases in humans, but earlier our experimental data should be verified in clinical laboratory.

Taking into account the literature reports on the involvement of prolactin (PRL) in the regulation of immunity against Toxoplasma gondii, we decided to check whether this parasite has the ability to bind the lactotrophic hormone. We examined T. gondii binding of sheep fluoresceine- and biotine-labeled prolactin isolated from pituitary (shPRL). In this work we announced for the first time that shPRL was bound to live tachyzoites of RH (type I) and ME49 (type II) strains. Furthermore, by use of competitive inhibition analysis, we confirmed that this binding was specific for both tested T. gondii strains.

The protozoan parasite Toxoplasma gondii has the ability to alter intermediate host behavior, most impressively the natural aversion to cat scent, to favor the predation by the definitive host. However, the underlying mechanism of the observed phenomenon still remains unknown. Since changes in the neurotransmitter level are postulated as a possible contributing factor, the aim of this work was to assess the monoamine systems activity in specified brain regions involved in the natural defense behaviors, emotion evaluation, and motor and sensory stimuli integration in experimentally T. gondii infected mice compared to uninfected controls. Taking into account the natural differences between genders, the experiments were carried out on both male and female mice. Our results revealed statistically significant changes in all tested monoamine systems with regard to both gender and time after T. gondii invasion. Acute toxoplasmosis was accompanied by a decrease in noradrenergic system activity in females and its slight increase in some brain areas of males. Acute invasion also induced a rise in serotonin system activity, mostly in males. The most striking observation was an increase in the dopamine release noted in acutely infected males. We discuss our results in terms of their possible contribution to T. gondii-induced intermediate host behavior alterations and parasite transmission and with regard to postulated relationship between T. gondii seroprevalence and occurrence of certain disorders such as schizophrenia in humans.

Toxoplasmosis is one of the world’s most widespread zoonoses caused by protozoan parasite Toxoplasma gondii. The development of an effective vaccine for controlling toxoplasmosis is an extremely important issue due to the serious clinical and veterinary outcomes of this parasitosis. The objective of this study was evaluation of vaccine potential of three trivalent subunit recombinant vaccines composed of rROP2 + rGRA4 + rSAG1, rROP2 + rROP4 + rGRA4 and rROP2 + rROP4 + rSAG1 against chronic toxoplasmosis in BALB/c (H-2d) mice. All tested vaccines provided a partial protection against challenge with tissue cysts of the low virulence DX T. gondii strain, but the strongest level of protection was induced by the mixtures of both rhoptry proteins (rROP2 and rROP4) administered with the dense granule rGRA4 antigen or the main surface rSAG1 protein. The average parasite burden in these groups of vaccinated BALB/c mice was reduced by 84% and 77%, respectively, compared to the control PBS-injected animals. The vaccine-induced protection was correlated with the development of cellular and humoral immune responses demonstrated by the antigen-specific in vitro proliferation of spleen cells, the specific antigen-induced in vitro synthesis of Th1-type cytokines, IFN-γ and IL-2, and the generation of the high titers of systemic antigen-specific IgG1 and IgG2a antibodies. This study completed and confirmed our earlier investigations in C3H/HeJ (H-2k) and C57BL/6 (H-2b) mouse strains on the utility of the tested trivalent recombinant antigen-cocktails as potential vaccines against chronic toxoplasmosis and showed that particularly rROP2 + rROP4 + rGRA4 and rROP2 + rROP4 + rSAG1 protein-combinations are very effective in the development of a high level of protection irrespective of the genetic backgrounds and innate resistance to toxoplasmosis of the laboratory mice. It makes these two mixtures of recombinant antigens very promising for further experiments.

During the development and effector phases of the anti-Toxoplasma response, the immunological system of a host is involved in several complex interactions with the endocrine system, and prolactin (PRL) is one of the most important hormones involved in immunoregulation. In this work, the influence of the recombinant human prolactin (rhPRL) on the viability, penetration, and intensity of intracellular proliferation of Toxoplasma gondii BK strain in vitro was evaluated. Using one murine (L929) and two human cell lines (Hs27 and HeLa), no toxic effect of the rhPRL on host cells was found (by determining cellular viability using MTT assay). A similar lack of rhPRL cytotoxic activity was found in the case of the extracellular tachyzoites of T. gondii BK. Replication of parasites in the presence of rhPRL was analyzed first by simultaneous addition of the hormone and the parasites into a microculture of the host cells (treatment during infection). No statistically significant changes in the intensity of parasite proliferation in all used host cells were found for a wide range of the hormone concentrations. However, pre-incubation of the tachyzoites with rhPRL resulted in a significant reduction (up to 36.15%) in the replication abilities of the parasite. Further experiments revealed that in fact, the inhibition of replication was caused by a limited capacity of the parasites to penetrate host’s cells as demonstrated by the reduced number of infected cells.

Recent studies have shown that hormones could induce anti-parasitic functions of the host immune system; thus, the aim of the present study was to estimate the seroprevalence of Toxoplasma gondii antibodies by an enzyme-linked immunosorbent assay in a Polish population of women and men with hyperprolactinaemia (n = 234) and hypoprolactinaemia (n = 41) and in a control group (n = 281) with the physiological level of prolactin (PRL). Women with hyperprolactinaemia revealed lower seroprevalence than those with normal PRL level (33.90% and 45.58%, respectively; p = 0.025). Detailed analysis of the results showed that twofold, threefold, fourfold and fivefold increase of the PRL concentration above the normal was correlated to the decrease of the T. gondii seroprevalence, but only in the group of women with a very high PRL level (>86 ng/ml) seroprevalence (12.50%) was significantly lower (p = 0.0004) than in the control subjects. These results confirm previously described suggestions on the relationship between hyperprolactinaemia and parasitic infection frequency. We postulate that a high level of PRL may be one of the important factors preventing T. gondii infection in women.

In vitro antifungal potency of a set of potassium N-acylhydrazinecarbodithioates was tested. Some of the studied salts displayed significant antifungal activity against Candida spp. at non-toxic concentration indicating a high selectivity of their anticandidal activity. In further study, on the example of conformational analysis, we have tested several force fields and semiempirical parametrizations in order to identify those that could be effectively used for modeling of this class of compounds.