Synthesis of N-heterocyclic amides based on (+)-camphoric acid and study of their antiviral activity and pharmacokinetics.

Efficient conditions for the synthesis of nitrogen-containing heterocyclic derivatives of (1R,3S)(+)-camphoric acid were selected. A series of heterocyclic compounds based on (+)-camphoric acid bearing pharmacophoric fragments was synthesized using the developed methodology. The compounds were tested for their antiviral activity against SARS-CoV-2 and H1N1 influenza viruses, and efficient inhibitors were identified that are of significant interest for further studies. The stability of the compounds and pharmaco-kinetics of the leader compound were studied when administered intragastrically and intramuscularly to mice at a dose of 200 mg kg-1 using the HPLC-MS/MS method.

Complex resistance of spring and winter bread wheat lines to biotic and abiotic stresses.

An original initial material of spring and winter bread wheat with group resistance to stem and leaf rust was developed using new donors of resistance to stem rust: winter soft wheat GT 96/90 (Bulgaria) and accession 119/4-06rw with genetic material of the species Triticum migushovae and (Aegilops speltoides and Secale cereale), respectively, a line of spring wheat 113/00i-4 obtained using the species Ae. triuncialis and T. kiharae, as well as spring accession 145/00i with genetic material of the species Ae. speltoides resistant to leaf rust. The transfer of effective Sr- genes to progeny was monitored using molecular markers. New lines underwent a f ield assessment of resistance to leaf and stem rust in the epiphytotic development of diseases in the Central Region of the Russian Federation, as well as in the North Caucasus and Western Siberia, and showed high resistance to these pathogens. Fourteen genotypes of spring wheat with group resistance to these diseases and parental forms that participated in the origin of the lines were evaluated for resistance to spot blotch (Cochliobolus sativus) and tan spot (Pyrenophora tritici-repentis) using isolates from Kazakhstan and Omsk in laboratory conditions. A highly resistant parental form of winter soft wheat from "Arsenal" collection 119/4-06rw (wheat-Ae. speltoides-rye hybrid 2n = 42) with group resistance to two spots, four medium-resistant genotypes to both isolates of tan spot from Kazakhstan and Omsk populations of the pathogen, as well as genotypes resistant to the Omsk isolate of P. tritici-repentis (parental form 113/00i-4 and lines 1-16i, 6-16i, 9-16i) were isolated. Among the lines of winter wheat, four were identif ied with group resistance to spot blotch and tan spot. Additionally, the stress resistance of the lines to NaCl salinization and prolonged f looding of seeds with water was evaluated at the early stages of ontogenesis in laboratory conditions. Lines 33-16i, 37-16i, 32- 16i and 9-16i showed a high ability to withstand excess moisture. Lines 33-16i, 37-16i, 32-16i and 3-16i were characterized by high salt tolerance, exceeding the average of 49.7 %. Among the winter genotypes, lines were identif ied with increased resistance to hypoxia (37-19w, 32-19w, 16-19w, 90-19w) and with increased salt tolerance (20- 19w, 9-19w, 37-19w, 90-19w), signif icantly exceeding the standard cv. Moskovskaya 39. The listed lines are of interest as sources of resistance to anaerobic and salt stress, as well as donors of resistance to a group of fungal diseases: leaf and stem rust and tan spot. We attribute the increased level of resistance of the new initial material to the presence of alien translocations in the original parental forms involved in the origin of the lines.

[Immunomodulatory effect of levamisole and administration of amitraz in dogs with uncomplicated generalized demodicosis]. / Imunomodulacný efekt levamizolu pri pouzití amitrazu u psov s nekomplikovanou generalizovanou demodikózou.

The immunomodulatory effect of levamisole (Decaris tbl.) in the course of acaricide therapy with amitraz (Taktic) on the functional activity of blood neutrophils (% of phagocytizing cells and ingestion capacity) and lymphocytes (blastogenic response to Con A) in dogs with uncomplicated generalized demodicosis (NGD) was studied. The level of examined parameters was evaluated before treatment, week 3 and 7 after the first application of these preparations; and compared with the values of NGD dogs treated only with amitraz and with those in clinically healthy dogs. In comparison with healthy dogs the initial level of examined activities of both cell populations was significantly depressed. A significantly earlier (4 weeks earlier) increase (when compared with values before treatment) of investigated activities of neutrophils and lymphocytes occurred in dogs treated with amitraz and levamisole in comparison with those in dogs treated only with amitraz. It was manifested especially significantly in phagocytosis, the ingestion capacity of neutrophils at this time of therapy has reached the level of those in healthy dogs. Functional activity of lymphocytes in both groups of NGD dogs has not reached a comparable value with that in healthy dogs either at the end of observation. The presented results indicate that significantly earlier improvement of functional activity of phagocytes and lymphocytes in demodectic dogs treated with amitraz and levamisole was connected with the immunorestorative effect of levamisole.

Lymphocyte blastogenesis to concanavalin A in dogs with localized demodicosis according to duration of clinical disease.

The aim of the study was to determine the degree of Con A induced lymphocyte blastogenesis in dogs with localized demodicosis (LD) within 1-3 and 6-8 weeks from appearance of the clinical signs. Ethidium bromide fluorescence assay was used for evaluation. In observation 9 clinically normal dogs, 6 dogs with LD a 4 dogs with generalized demodicosis (GD) were used. The results showed a statistically significant depression (P < 0.01) of blastogenesis in the LD dogs in comparison with that in the healthy dogs (Fig. 1). Responses to Con A were normal in dogs with LD in 1-3 weeks. However, a significantly depressed response to Con A (P < 0.025-0.001) was demonstrated in the LD dogs in 6-8 weeks (average 6.7 weeks) and it was comparable with that in the GD dogs with the duration of clinical disease on average for 8.7 weeks (Fig. 2; Tab. II). Thus, immunosuppression is not a necessary condition for dogs to develop spontaneous clinical LD and immunosuppression develops with the clinical signs of disease.

Evaluation of canine lymphocyte blastogenesis prior and after in vitro suppression by dog demodicosis serum using ethidium bromide fluorescence assay.

The mitogen induced blastogenic response of lymphocytes from normal dogs and dogs with generalized demodicosis (GD) was measured by the ethidium bromide (EB) fluorescence assay. Serum from GD dogs significantly suppressed the in vitro reactivity to Con A of peripheral blood lymphocytes (PBL) from normal dogs and GD dogs, however with a different percentage of suppression 40.6 and 81.2%, respectively. As a result, the degree of lymphocyte blastogenesis suppression in GD dogs did not parallel the immunosuppressive potency of their serum (Tab. IV). The data indicate that PBL obtained from GD dogs did not respond to Con A as well in the presence of serum from normal dogs as did PBL from normal dogs (Tab. IV). In one third of examined GD dogs a similar situation was described also by Hirsh et al. (1975). The basis for this cellular modified response is unknown. It does not appear that the age or the chronicity of the disease are related to this observation. Further studies are necessary to elucidate this relation. The GD dogs showed not only a significant depression of the lymphocyte response to Con A but also enhancement of the ability of unstimulated cells to proliferate was also observed (Tab. IV). Similar observation was reported by others (Barriga et al., 1992). The meaning of this is not clear at present. This finding is discussed in the light of proposed different effects of the parasite or the host's reactivity to the parasite on different subsets of lymphocytes. No significant difference of PBL responsiveness to Con A between healthy dogs with respect to the age (Tab. III) and the time of examination (compare results in Tabs. I and IV) was observed. Autologous serum showed a better responsiveness of normal canine lymphocytes to Con A than fetal calf serum (FCS). It is suggested that the use of FCS might lead to an erroneous judgement (Tab. I). Both lectins, Con A and PHA induced cell proliferation of healthy dogs in very similar amount (Tab. II). Our results indicated that EB fluorescence assay is a useful method for detection a respondence of canine lymphocyte blastogenesis.

[Seasonal effect on serum levels of thyroid hormones in German shepherds and dachshunds and their health status]. / Sezónnost a jej vplyv na hladiny tyroidných hormonóv v krvnom sére nemeckých ovciakov, jazvecíkov a ich zdravotný stav.

A relatively frequent prevalence of dermatoses in summer has drawn our attention. Dermatoses of endocrine origin occur very often. We have noticed the deterioration of skin changes in animals with hypothyroidism. Bubeník et al. (1983), Webster et al. (1991), Reiter et al. (1988) reported that changes in concentrations of thyroid hormones were found in fallow-deer, sheep and hamsters due to the effect of temperature and season. Based upon this knowledge we have decided to observe the health status and function of the thyroid gland in two randomly selected groups of various size dogs--German shepherd and dachshund during four seasons. We observed following parameters: concentration of triiodothyronine (T3), thyroxine (T4), cholesterol (Chol) and total lipids (TL) in the blood serum, average temperatures in individual seasons. Blood was always withdrawn fasting in the morning from vena antebrachii. Concentrations of T3 and T4 were determined by the commercial kits RIA-test-T4 and RIA-test-T3 (Human-Lab, Kosice, Slovak Republic). The levels of cholesterol and total lipids were determined by the BIO-LA-tests (Lachema, Brno, Czech Republic). March, April, May were included into spring season; June, July, August into summer; September, October, November into autumn; and December, January, February into winter. The Slovak Hydrometeorologic Institute in Kosice provided the values of average temperatures in observed seasons. The average temperatures in individual seasons were the following: spring +9.8 degrees C, summer +18.4 degrees C, autumn +8.5 degrees C, winter -1.2 degrees C. During the observed period concentrations of cholesterol and total lipids ranged within the reference values in both breeds.(ABSTRACT TRUNCATED AT 250 WORDS)

[Electron microscopy immunolocalization of ribosomal ribonucleoproteins using autoantibodies from patients with systemic lupus erythematosus]. / Elektrónovomikroskopická imunolokalizácia ribozomálnych ribonukleoproteínov autoprotilátkami pacientov so systémovým lupus erythematosus.

Serum of patients against rRNP was tested by Western blot method. Four ribonucleoproteins (15, 16, 36 and 38 kDa) specifically reacted with the antiserum used. The autoantibodies were used for immunolocalization of antigenic structures by immunogold method on ultrathin cryosections of hepatocytes, cumulus cells of antral follicle and spermatocytes. Mice and hamsters were used. The cytoplasm appeared to be labelled most intensively. Gold particles were loosely arranged in the cytoplasm (cumulus cells) or they were associated with endoplasmatic reticulum (hepatocytes). Nucleoli were labelled by a lower incidence of the marker. Gold particles were found over the dense fibrillar component bordering on the granular component. In the cytoplasm individual gold particles were observed. (Fig. 7, Ref. 31.).