Effect of special types of bread with select herbal components on postprandial glucose levels in diabetic patients.

BACKGROUND: Nutrition recommendations in patients with type 2 diabetes mellitus (T2DM) are to consume rye or integral bread instead of white bread. A positive effect on glucoregulation has been achieved by enriching food with various biologically active substances of herbal origin, so we formulated an herbal mixture that can be used as a supplement for a special type of bread (STB) to achieve better effects on postprandial glucose and insulin levels in patients with T2DM. AIM: To compare organoleptic characteristics and effects of two types of bread on postprandial glucose and insulin levels in T2DM patients. METHODS: This trial included 97 patients with T2DM. A parallel group of 16 healthy subjects was also investigated. All participants were given 50 g of rye bread and the same amount of a STB with an herbal mixture on 2 consecutive days. Postprandial blood glucose and insulin levels were compared at the 30th, 60th, 90th and 120th min. A questionnaire was used for subjective estimation of the organoleptic and satiety features of the two types of bread. RESULTS: Compared to patients who consumed rye bread, significantly lower postprandial blood glucose and insulin concentrations were found in T2DM patients who consumed STB. No relevant differences were found among the healthy subjects. Subjectively estimated organoleptic and satiety characteristics are better for STB than for rye bread. CONCLUSION: STB have better effects than rye bread on postprandial glucoregulation in T2DM patients. Subjectively estimated organoleptic and satiety characteristics are better for STB than for rye bread. Therefore, STB can be recommended for nutrition in T2DM patients.

Pharmacological effects of monoterpene carveol on the neuromuscular system of nematodes and mammals.

The control of parasitic nematode infections relies mostly on anthelmintics. The potential pharmacotherapeutic application of phytochemicals, in order to overcome parasite resistance and enhance the effect of existing drugs, is becoming increasingly important. The antinematodal effects of carveol was tested on the free-living nematode Caenorhabditis elegans and the neuromuscular preparation of the parasitic nematode Ascaris suum. Carveol caused spastic paralysis in C. elegans. In A. suum carveol potentiated contractions induced by acetylcholine (ACh) and this effect was confirmed with two-electrode voltage-clamp electrophysiology on the A. suum nicotinic ACh receptor expressed in Xenopus oocytes. However, potentiating effect of carveol on ACh-induced contractions was partially sensitive to atropine, indicates a dominant nicotine effect but also the involvement of some muscarinic structures. The effects of carveol on the neuromuscular system of mammals are also specific. In micromolar concentrations, carveol acts as a non-competitive ACh antagonist on ileum contractions. Unlike atropine, it does not change the EC50 of ACh, but reduces the amplitude of contractions. Carveol caused an increase in Electrical Field Stimulation-evoked contractions of the isolated rat diaphragm, but at higher concentrations it caused an inhibition. Also, carveol neutralized the mecamylamine-induced tetanic fade, indicating a possibly different pre- and post-synaptic action at the neuromuscular junction.

The occurrence of 40K and 137Cs radioactivity in mosses during 2015-2019 in the Djerdap National Park (E. Serbia).

The radiation status of the national park (NP) Djerdap (Eastern Serbia) is characterized using bioindicators (mosses). Mosses (16 species, 156 samples) were collected randomly within the area of NP Djerdap during the month of June, periodically from 2015 to 2019. Samples were collected in the regions of Dobra, Donji Milanovac, and Tekija. Within the mosses, the presence of 40 K and 137Cs is regarded as a good indicator of radionuclides present in the environment due to their easy interchangeability with 39 K highly present in living moss organisms. The activity concentrations of gamma ray-emmiting radionuclides in samples were determined using high-resolution gamma ray spectrometry, an HPGe-ORTEC/Ametek detector. The determining activity concentrations of 40 K and 137Cs in collected samples were as follows: for 40 K from 31.4 to 721 Bq kg-1and for 137Cs varied from 2.6 to 908 Bq kg-1. The average activity concentrations of 40 K and 137Cs (Bq kg-1) in mosses in the period 2015-2019 were the lowest in moss samples collected in the Dobra region, and the highest in the area of Donji Milanovac. The most prevalent collected moss species within the Djerdap National Park was Hypnum cupressiforme. The determined activity concentrations in H. cupressiforme of 137Cs for the whole region of NP Djerdap for all 5 years was 78.1 ± 70.3 Bq kg-1 and of 40 K was 181 ± 86.1 Bq kg-1.

Chemical, Analytical and Pharmacokinetic Characterisation of RO7304898, an API Consisting of Two Rapidly Interconverting Diastereoisomers.

PURPOSE: Exploration of the chemical, analytical and pharmacokinetic properties of the API, RO7304898, an allosteric EGFR inhibitor, intended to be developed as a mixture of two rapidly interconverting diastereoisomers with composition ratio of approximately 1:1. METHODS: Assessment of diastereoisomer stereochemistry, interconversion rates, binding to EGFR protein, metabolic stability and in vivo PK in Wistar-Han rats was conducted. RESULTS: The two diastereoisomers of the API undergo fast interconversion at physiologically relevant pH and direct EGFR binding studies revealed diastereoisomer B to be the active moiety. Pharmacokinetic studies in rat revealed a low-moderate total plasma clearance of the API along with similar plasma concentration-time profiles for diastereoisomers A and B, and the diastereoisomeric ratio reached stable equilibrium favoring formation of the potent diastereoisomer B. In in vitro incubations, the API was metabolically stable in plasma and hepatocyte suspension incubations in all species tested except that of rat hepatocytes. Additionally, only small species differences in the A:B composition were observed in vitro with the potent diastereoisomer B being the predominant form. CONCLUSIONS: We demonstrated that the API, a mixture of two diastereoisomers; A (impotent) and B (potent), undergoes rapid interconversion which is faster than the apparent distribution and elimination rates of the individual diastereoisomers in vivo in rat, serving to diminish concerns that separate diastereoisomer effects may occur in subsequent pharmacologic and pivotal toxicological studies. Whilst vigilant monitoring of the diastereoisomeric ratio will need to be continued, this data adds confidence on the development pathway for this API to the clinic.

Action of Carvacrol on Parascaris sp. and Antagonistic Effect on Nicotinic Acetylcholine Receptors.

Parascaris sp. is the only ascarid parasitic nematode in equids and one of the most threatening infectious organisms in horses. Only a limited number of compounds are available for treatment of horse helminthiasis, and Parascaris sp. worms have developed resistance to the three major anthelmintic families. In order to overcome the appearance of resistance, there is an urgent need for new therapeutic strategies. The active ingredients of herbal essential oils are potentially effective antiparasitic drugs. Carvacrol is one of the principal chemicals of essential oil from Origanum, Thymus, Coridothymus, Thymbra, Satureja and Lippia herbs. However, the antiparasitic mode of action of carvacrol is poorly understood. Here, the objective of the work was to characterize the activity of carvacrol on Parascaris sp. nicotinic acetylcholine receptor (nAChR) function both in vivo with the use of worm neuromuscular flap preparations and in vitro with two-electrode voltage-clamp electrophysiology on nAChRs expressed in Xenopus oocytes. We developed a neuromuscular contraction assay for Parascaris body flaps and obtained acetylcholine concentration-dependent contraction responses. Strikingly, we observed that 300 µM carvacrol fully and irreversibly abolished Parascaris sp. muscle contractions elicited by acetylcholine. Similarly, carvacrol antagonized acetylcholine-induced currents from both the nicotine-sensitive AChR and the morantel-sensitive AChR subtypes. Thus, we show for the first time that body muscle flap preparation is a tractable approach to investigating the pharmacology of Parascaris sp. neuromuscular system. Our results suggest an intriguing mode of action for carvacrol, being a potent antagonist of muscle nAChRs of Parascaris sp. worms, which may account for its antiparasitic potency.

Interaction of agonists of a different subtype of the nAChR and carvacrol with GABA in Ascaris suum somatic muscle contractions.

Resistance of parasitic nematodes to anthelmintic drugs is a growing problem in human and veterinary medicine. The molecular mechanisms by which nematodes become resistant are different, but certainly one of the possible processes involves changing the drug binding site on the specific receptor. The significance of changes in individual subtypes of nicotinic acetylcholine receptors (nAChRs) for the development of resistance has not been clarified in detail. This study investigates the interaction of antinematodal drugs, agonist of different types of nAChRs and carvacrol with gamma aminobutyric acid (GABA) on the contractions of parasitic nematode A. suum. In our study, GABA (3 µM) produced significant increase of contractile EC50 value for pyrantel, and nonsignificant for bephenium and morantel, from 8.44 to 28.11 nM, 0.62 to 0.96 µM, and 3.72 to 5.69 nM, respectively. On the other hand, the maximal contractile effect (R max) did not change in the presence of GABA. However, when A. summ muscle flaps were incubated with GABA 3 µM and carvacrol 100 µM, the EC50 value of pyrantel, bephenium, and morantel was increased significantly to 44.62 nM, 1.40 µM, and nonsignificantly to 7.94 nM, respectively. Furthermore, R max decreased by 70, 60, and 65%. Presented results indicate that the combined use of GABA receptor agonists and nicotinic receptor antagonists can effectively inhibit the neuromuscular system of nematodes, even when one of the nicotinic receptor subtypes is dysfunctional, due to the potential development of resistance.

Potential modulating effect of the Ascaris suum nicotinic acetylcholine receptor (nAChR) by compounds GSK575594A, diazepam and flumazenil discovered by structure-based virtual screening approach.

Parasitic infections are a widespread health problem and research of novel anthelmintic compounds is of the utmost importance. In this study we performed a virtual screening campaign by coupling ligand-based pharmacophore, homology modeling and molecular docking. The virtual screening campaign was conducted using a joined pool of the Drugbank database and a library of purchasable compounds in order to identify drug like compounds with similar pharmacological activity. Our aim was to identify compounds with a potential antihelmintic modulatory effect on nicotinic acetylcholine receptors (nAChR). We derived a 3D pharmacophore model based on the chemical features of known Ascaris suum nAChR modulators. To evaluate the in silico predictions, we tested selected hit compounds in contraction assays using somatic muscle flaps of the Ascaris suum neuromuscular tissue. We tested the modulatory effects of GSK575594A, diazepam and flumazenil hit compounds on nematode contractions induced by acetyl choline (ACh). The compound GSK575594A (3 µM) increased the Emax by 21 % with the EC50 dose ratio of 0.96. Diazepam (100 µM) decreased the Emax by 15 % (1.11 g to 0.95 g) with the EC50 ratio of 1.42 (shifted to the left from 11.25 to 7.93). Flumazenil decreased the EC50 value (from 11.22 µM to 4.88 µM) value showing dose ratio of 2.30, and increased the Emax by 4 % (from 1.54 g to 1.59 g). The observed biological activity was rationalized by molecular docking calculations. Docking scores were calculated against several binding sites within the Ascaris suum homology model. We constructed the homology model using the ACR-16 subunit sequence. The compound GSK575594A showed strong affinity for the intersubunit allosteric binding site within the nAChR transmembrane domain. The binding modes of diazepam and flumazenil suggest that these compounds have a comparable affinity for orthosteric and allosteric nAChR binding sites. The selected hit compounds displayed potential for further optimization as lead compounds. Therefore, such compounds may be useful in neutralizing the growing resistance of parasites to drugs, either alone or in combination with existing conventional anthelmintics.

The use of collagen porcine dermal matrix and connective tissue graft with modified coronally advanced tunnel technique in the treatment of multiple adjacent type I gingival recessions: A randomized, controlled clinical trial.

OBJECTIVE: To assess the clinical efficacy and esthetic outcome of porcine-derived dermal collagen matrix in comparison with connective tissue graft in the treatment of multiple adjacent gingival recessions (MAGR), 6 and 12 months after the surgery. MATERIALS AND METHODS: Twenty patients with bilateral type I MAGR were treated randomly with porcine-derived dermal collagen matrix (test site) or connective tissue graft (control site) in combination with a modified coronally advanced tunnel technique. The primary objectives were to evaluate the mean and complete root coverage. The secondary objectives were to assess keratinized tissue width, gingival thickness gain, and root coverage esthetic score. RESULTS: Six and 12 months postoperatively, both groups achieved significant improvements in all clinical parameters compared to baseline, with no statistically significant differences between the groups. Mean root coverage change (Δ12m - 6 m) was statistically significant between the groups in favor of connective tissue graft, and twice as many patients exhibited a complete coverage of all recessions in the control group than the test group. CONCLUSION: The porcine-derived dermal collagen matrix combined with a modified coronally advanced tunnel technique resulted in satisfactory clinical and esthetic outcomes, which were similar to connective tissue graft. CLINICAL SIGNIFICANCE: Porcine-derived dermal collagen matrix (XDM) may be proposed as a substitute for connective tissue graft in multiple adjacent recession treatment due to successful root coverage, a significant increase of gingival thickness, and high esthetic outcomes. The clinical benefits for the use of XDM could be: (a) second surgical wound avoidance, (b) patient discomfort decrease, and (c) lower complications' rate.

Publisher Correction: OpenSWATH enables automated, targeted analysis of data-independent acquisition MS data.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Carvacrol acts as a potent selective antagonist of different types of nicotinic acetylcholine receptors and enhances the effect of monepantel in the parasitic nematode Ascaris suum.

The neuromuscular system of parasitic nematodes has proven to be an efficient pharmacological target for antihelmintics. Some of the most frequently used antiparasitic drugs are agonists or antagonists of nicotinic acetylcholine receptors (nAChRs). The antinematodal mechanism of action of carvacrol involves the inhibition of parasite muscle contraction. We have examined the interaction of carvacrol with antinematodal drugs that are agonists of different subtypes of nAChRs and monepantel, which is a non-competitive antagonist of this receptor in A. suum. Additionally, we investigated the effect of carvacrol on the muscle type of nAChRs in the mammalian host. As orthosteric agonists of nAChR, pyrantel, morantel and befinijum lead to dose-dependent contractions of the neuromuscular preparation of Ascaris suum. Carvacrol 100 µM decreased the Emax of pyrantel, morantel and bephenium by 29%, 39% and 12 %, 39 % and 12 % respectively. The EC50 ratio was 3.43, 2.95 and 2.47 for pyrantel, morantel and bephinium, respectively. Carvacrol 300 u µM reduces the Emax of pyrantel, morantel and bephenium by 71%, 80% and 75 %, 80 % and 75 % respectively. The EC50 ratio for pyrantel, morantel and bephenium was 3.88, 3.19 and 4.83 respectively. Furthermore, carvacrol enhances the inhibitory effect of monepantel on A. suum contractions, which may have an effective clinical application. On the other hand, tested concentrations of carvacrol did not significantly affect the EFS-induced contractions of the rat diaphragm, indicating a lack of interaction with the postsynaptic nAChR at the muscle end plate in mammals, but the highest concentration (300 µM) caused a clear tetanic fade. Carvacrol exhibited a time and dose-dependent effect on the Rota-rod performances of rats with a high value of the ED50 (421.6 mg/kg). In our research, carvacrol dominantly exhibited characteristics of a non-competitive antagonist of nAChR in A. suum, and enhances the inhibitory effect of monepantel. The combination of monepantel and carvacrol may be clinically very effective, and the carvacrol molecule itself can be used as a promising platform for the development of new anthelmintic drugs.

An insight into chemical composition and bioactivity of 'Prokupac' red wine.

Autochthonous variety 'Prokupac' (Vitis vinifera L.) red wines with the addition of selected aromatic herbs (Artemisia absinthium, Cinnamomum zeylanicum, Glycyrrhiza glabra and Pimpinella anisum L.) were evaluated for chemical composition and biological activity. Furthermore, their polyphenolic profiles were determined by HPLC-DAD. While total phenolic (TPC) and flavonoid (TFC) contents, along with antioxidant activity, were significantly higher in all examined wine samples, the content of total anthocyanins was decreased, compared to a pure 'Prokupac' wine, used as the control one. On the other hand, 'Prokupac' wines with the addition of cinnamon (S. zeylanicum) and wormwood (A. absinthium) displayed highest antioxidant (EC50, 0.021 ± 0.001 mg/mL) and antibacterial (Enterococcus faecalis, MIC/MBC 15.63/62.50 µL/mL) activities, respectively. The study showed that 'Prokupac' wine with the addition of cinnamon was significantly enriched both with TPC and TFC, compared to control wine (p < 0.05), which may contribute to its market potential.

Solitary Fibrous Tumor of the Dorsal Tongue Area.

Solitary fibrous tumor (SFT) is a rare tumor occurring in pleura or extrapleural areas. The tongue is infrequently affected, in less than 25 published cases. A female patient, 35 years of age, noticed an oval mass in the posterior dorsal part of the tongue. The operated mass was nodule, 10 mm in size, sharply circumscribed, rather firm. The histology shows uniform CD34 positive spindle tumor cells. The diagnosis of benign SFT of the tongue was made.

Menthol acts as a positive allosteric modulator on nematode levamisole sensitive nicotinic acetylcholine receptors.

The ongoing and widespread emergence of resistance to the existing anti-nematodal pharmacopeia has made it imperative to develop new anthelminthic agents. Historically, plants have been important sources of therapeutic compounds and offer an alternative to synthetic drugs. Monoterpenoids are phytochemicals that have been shown to produce acute toxic effects in insects and nematodes. Previous studies have shown nicotinic acetylcholine receptors (nAChRs) to be possible targets for naturally occurring plant metabolites such as carvacrol and carveol. In this study we examined the effects of monoterpenoid compounds on a levamisole sensitive nAChR from Oesophagostomum dentatum and a nicotine sensitive nAChR from Ascaris suum. We expressed the receptors in Xenopus laevis oocytes and used two-electrode voltage-clamp to characterize the effect of various compounds on these cys-loop receptors. At 100 µM the majority of these compounds acted as antagonists. Interestingly, further experiments revealed that both 0.1 µM and 10 µM menthol potentiated acetylcholine and levamisole responses in the levamisole sensitive receptor but not the nicotine sensitive receptor. We also investigated the effects of 0.1 µM menthol on the contractility of A. suum somatic muscle strips. Menthol produced significant potentiation of peak contractions at each concentration of acetylcholine. The positive allosteric modulatory effects of menthol in both in vivo and in vitro experiments suggests menthol as a promising candidate for combination therapy with cholinergic anthelmintics.

Monepantel is a non-competitive antagonist of nicotinic acetylcholine receptors from Ascaris suum and Oesophagostomum dentatum.

Zolvix® is a recently introduced anthelmintic drench containing monepantel as the active ingredient. Monepantel is a positive allosteric modulator of DEG-3/DES-2 type nicotinic acetylcholine receptors (nAChRs) in several nematode species. The drug has been reported to produce hypercontraction of Caenorhabditis elegans and Haemonchus contortus somatic muscle. We investigated the effects of monepantel on nAChRs from Ascaris suum and Oesophagostomum dentatum heterologously expressed in Xenopus laevis oocytes. Using two-electrode voltage-clamp electrophysiology, we studied the effects of monepantel on a nicotine preferring homomeric nAChR subtype from A. suum comprising of ACR-16; a pyrantel/tribendimidine preferring heteromeric subtype from O. dentatum comprising UNC-29, UNC-38 and UNC-63 subunits; and a levamisole preferring subtype (O. dentatum) comprising UNC-29, UNC-38, UNC-63 and ACR-8 subunits. For each subtype tested, monepantel applied in isolation produced no measurable currents thereby ruling out an agonist action. When monepantel was continuously applied, it reduced the amplitude of acetylcholine induced currents in a concentration-dependent manner. In all three subtypes, monepantel acted as a non-competitive antagonist on the expressed receptors. ACR-16 from A. suum was particularly sensitive to monepantel inhibition (IC50 values: 1.6 ±â€¯3.1 nM and 0.2 ±â€¯2.3 µM). We also investigated the effects of monepantel on muscle flaps isolated from adult A. suum. The drug did not significantly increase baseline tension when applied on its own. As with acetylcholine induced currents in the heterologously expressed receptors, contractions induced by acetylcholine were antagonized by monepantel. Further investigation revealed that the inhibition was a mixture of competitive and non-competitive antagonism. Our findings suggest that monepantel is active on multiple nAChR subtypes.

In vitro and in vivo antimelanoma effect of ethyl ester cyclohexyl analog of ethylenediamine dipropanoic acid.

Melanoma, an aggressive skin tumor with high metastatic potential, is associated with high mortality and increasing morbidity. Multiple available chemotherapeutic and immunotherapeutic modalities failed to improve survival in advanced disease, and the search for new agents is ongoing. The aim of this study was to investigate antimelanoma effects of O,O-diethyl-(S,S)-ethylenediamine-N,N'di-2-(3-cyclohexyl) propanoate dihydrochloride (EE), a previously synthesized and characterized organic compound. Mouse melanoma B16 cell viability was assessed using acid phosphatase, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, sulforhodamine B, and lactate dehydrogenase assays. Apoptosis and autophagy were investigated using flow cytometry, fluorescence and electron microscopy, and western blotting. In vivo antitumor potential was assessed in subcutaneous mouse melanoma model after 14 days of treatment with EE. Tumor mass and volume were measured, and RT-PCR was used for investigating the expression of autophagy-related, proapoptotic, and antiapoptotic molecules in tumor tissue. Investigated organic compound exerts significant cytotoxic effect against B16 cells. EE induced apoptosis, as confirmed by phosphatidyl serine externalisation, caspase activation, and ultrastructural features typical for apoptosis seen on fluorescence and electron microscopes. The apoptotic mechanism included prompt disruption of mitochondrial membrane potential and oxidative stress. No autophagy was observed. Antimelanoma action and apoptosis induction were confirmed in vivo, as EE decreased mass and volume of tumors, and increased expression of several proapoptotic genes. EE possesses significant antimelanoma action and causes caspase-dependent apoptosis mediated by mitochondrial damage and reactive oxygen species production. Decrease in tumor growth and increase in expression of proapoptotic genes in tumor tissue suggest that EE warrants further investigation as a candidate agent in treating melanoma.

Two opposite dose-dependent effects of diazinon on the motor activity of the rat ileum.

Acute poisoning with OPs may lead to a range of neurological effects, which cannot be explained by AChE inhibition alone. Several OPs interact directly with cholinergic receptors in mammals, but such data does not exist for invertebrates. The aim of current study was to investigate the direct and indirect effects of diazinon on the contractions of rat ileum and to compare those effects on the nervemuscle preparation of the Ascaris suum. In the presence of increasing concentrations of diazinon (3, 10 and 30nM), EFS-induced ileal contractions were increased significantly. In the same preparation, diazinon 3nM, significantly increased contractions induced by EFS, but did not affect the contractions caused by 5MFI. Contrarily, 1µM of diazinon significantly and reversibly inhibited the EFS-induced ileal contractions. Diazinon exhibited competitive and non-competitive inhibitions of 5MFI induced contractions. The control EC50 of 5MFI was 2.48µM with Rmax=1.88g. In the presence of diazinon, EC50 was 12.45µM, while Rmax was reduced to 0.43g. After washing, the EC50 and Rmax values were again closer to the control level (3.80µM and 1.04g). Diazinon 1µM did not inhibit Ascaris suum contractions caused by ACh, but it increased the Rmax. Diazinon in our study exhibits two opposite effects on the motor activity of the ileum. In low nanomolar concentrations the dominat is its effect on AChE and the stimulation of contractions. Furthermore, in concentrations that approach micromolar values diazinon has a direct inhibitory effect on muscarinic receptors. The direct inhibitory effect of diazinon on A. suum contractions was not found.

DIAGNOSIS AND THERAPY OF LIVER FLUKE (FASCIOLOIDES MAGNA) INFECTION IN FALLOW DEER (DAMA DAMA) IN SERBIA.

Giant liver fluke ( Fascioloides magna ) infection is an important health problem of cervids in southeastern Europe. We measured the prevalence and intensity of infection with F. magna in a fenced area near the Danube River in the South Backa District of Serbia. Parasitologic, pathomorphologic, and histopathologic examinations were conducted from November 2007 to February 2008, beginning with a population of 127 adult fallow deer ( Dama dama ). After a positive diagnosis, therapy with triclabendazole-medicated corn was applied. Deer were treated at four baiting stations, using medicated feed providing triclabendazole at an estimated dose of 10-14 mg/kg of body weight per deer. Treatment lasted for 7 d in early February 2008 and an additional 7 d 2 wk later. For the complete success of pharmacotherapy it was necessary to prevent any contact of deer with the snail intermediate host ( Galba truncatula ). Intervention in the habitat, removing grass and low vegetation, and draining ponds reduces the possibility of contact. Six months after the treatment, livers of hunted deer were reddish, with fibrous tracks; pigmentation and cysts in the parenchyma were surrounded by a fibrous capsule and their fecal samples contained no eggs of F. magna . Over the following years, livers of hunted deer were negative, and the last control cull in March 2015 confirmed complete absence of infection. We reconfirmed the presence of giant liver flukes in fallow deer in Serbia, apparently the result of natural spread across the Danube from Hungary and Croatia. We also report that the treatment of deer with triclabendazole-medicated corn is an effective method for administration of therapeutic doses of drug in semicaptive deer. Interventions in the environment are necessary to prevent recontact of deer with habitats used by the snail intermediate host, and enable the success of the therapy.

The Association Between Periodontal Inflammation and Labor Triggers (Elevated Cytokine Levels) in Preterm Birth: A Cross-Sectional Study.

BACKGROUND: Periodontitis is considered to be a risk factor for preterm birth. Mechanisms have been proposed for this pathologic relation, but the exact pathologic pattern remains unclear. Therefore, the objective of the present study is to evaluate levels of four major labor triggers, prostaglandin E2 (PGE2), interleukin (IL)-1ß, IL-6, and tumor necrosis factor (TNF)-α, in gingival crevicular fluid (GCF) and serum samples between women with preterm birth (PTB) and full-term birth (FTB) and correlate them with periodontal parameters. METHODS: PGE2, IL-1ß, IL-6, and TNF-α levels were estimated using enzyme-linked immunosorbent assays in GCF and serum samples collected 24 to 48 hours after labor from 120 women (60 FTB, 60 PTB). RESULTS: Women with PTB exhibited significantly more periodontitis, worse periodontal parameters, and increased GCF levels of IL-6 and PGE2 compared with the FTB group; there were no significant differences in serum levels of measured markers. GCF levels of IL-1ß, IL-6, and PGE2 and serum levels of TNF-α and PGE2 were significantly higher in women with periodontitis compared with periodontally healthy women. Serum levels of PGE2 were positively correlated with probing depth (PD) and clinical attachment level (CAL) as well as with GCF levels of TNF-α in women with PTB. CONCLUSIONS: Women with PTB demonstrated worse periodontal parameters and significantly increased GCF levels of IL-6 and PGE2 compared with those with FTB. Based on significant correlations among serum PGE2 and PD, CAL, and GCF TNF-α in PTB, periodontitis may cause an overall increase of labor triggers and hence contribute to preterm labor onset.

Pharmacological and morphological characteristics of the muscular system of the giant liver fluke (Fascioloides magna - Bassi 1875).

Motility is required for feeding, reproduction and maintenance of the fluke in the host's liver. According to that, the neuromuscular system can be an attractive drugable target for chemotherapy. Musculature of the Fascioloides magna is organized into three layers, an outer circular layer, beneath this layer the longitudinal layer, and third, the oblique, or diagonal layer underlies the longitudinal layer. In our study, the administration of atropine or caffeine did not cause classic muscle contractions of F. magna muscle strips. However, the Electrical Field Stimulation (EFS) induced stable and repeatable contractions, which enabled us to examine their sensitivity to the various substances. Acetylcholine (ACh) (300 µM and 1 mM), caused only a slight relaxation, without affecting the amplitude of spontaneous contractions or the amplitude of contractions induced by EFS. Contrary to that, atropine (100 µM) caused a significant increase in the basal tone and an increase of EFS-induced contractions. If acetylcholine is an inhibitory neurotransmitter in trematodes, the described effects of atropine are achieved by the blockade of inhibitory neurotransmission. On the other hand, with respect to the process of excitation-contraction coupling, the plant alkaloid ryanodine (30 µM) significantly reduced the basal tone, as well as EFS-induced contractions of F. magna muscle strips. Ryanodine inhibited the potentiating effect of atropine on the basal tone and contractions caused by EFS, which indicates that the contractile effect of atropine is dependent on Ca(++) release from intracellular stores. Caffeine (500 µM) caused relaxation of fluke muscle strips and at the same time significantly enhanced the EFS-induced contractions. Both effects of caffeine can be explained by entry of extracellular Ca(++) into muscle cells. The muscle contractility of F. magna depends both on the entry of extracellular calcium, and calcium release from intracellular stores, which are under the control of RyRs. Our results also suggest that antitrematodal drugs could potentially be developed from substances with selective anti-cholinergic activity.

Clinical and CBCT-based diagnosis of furcation involvement in patients with severe periodontitis.

OBJECTIVE: The aim of this study was to compare the use of periodontal probing and cone beam computed tomography (CBCT) images in the diagnosis of furcation involvement (FI) in patients with chronic generalized severe periodontitis. METHOD AND MATERIALS: Fifteen patients with chronic generalized severe periodontitis were included in this study. In total, 174 furcation sites (all in molar teeth) were analyzed. FI was assessed at three sites (buccal, mesiopalatal, and distopalatal) of maxillary molars, and at two sites (buccal and oral) of mandibular molars. FI was assessed both clinically (periodontal probing) and on CBCT images, using a dichotomous scale (present/absent). The agreement between clinical and CBCT-based findings was calculated. RESULTS: FI were more often detected by means of CBCT than by means of clinical examination. Agreement between the evaluation methods was present in 46.9% of cases (63.3% in maxilla, 45.0% in mandible). FI detected clinically was confirmed by means of CBCT in 24% of the evaluated sites. The largest agreement (73.7%) in FI detection was found in the distopalatal maxillary sites between CBCT and clinical probing. The smallest agreement (36.6%) was found in the buccal sites of the mandibular molars, in which 63.3% of FI were detected using CBCT only, but not clinically. CONCLUSION: The number of FI detected by means of CBCT was larger than by means of periodontal probing. In those cases in which chronic generalized severe periodontitis is clinically diagnosed, and surgical treatment is necessary, CBCT may be suggested as an adjunct tool for FI assessment.