Veterinary drug Trametin obtained on the basis of Trametes pubescens xylotroph fungi: its effect on the biosynthesis of interferons and its prophylactic activity against calf respiratory diseases

Given the spread of bacterial and viral diseases in young farm animals, the use of interferons and drugs to stimulate their biosynthesis has gained relevance. In a previous study, we examined the effect of a veterinary drug Trametin produced on the basis of Trametes pubescens (Shumach.: Fr.) Pilat. on the biosynthesis of interferons in the blood of mice. The present work is aimed at studying the biosynthesis dynamics of α- and γ-interferons when using Trametin and studying its prophylactic activity in calves. It is shown that a single oral administration of Trametin in doses ranging from 15 to 60 mg/kg causes a dose-dependent induction and production of γ-interferon in the blood of mice, whose maximum content reaches 1337.0±93.0 pg/mL at 48 h after administering a dose of 30 mg/kg. With a Trametin dose increase from 15 to 30 mg/kg, the level of α-interferon production rises to 1388.0±84.0 pg/mL at 48 h after administration. At a Cycloferon dose of 4.5 mg/kg, the production level of α-interferon and γ-interferon amounts to 1455.47±84.2 and 1447.0±90.0 pg/mL, respectively. The immunostimulatory properties of Trametin are confirmed by a scientific and economic experiment conducted using immunocompromised calves. In our studies, an immunological test of calf blood performed prior to and following the administration of Trimetin and Cycloferon constitutes criteria for the prophylactic activity of these drugs. The prophylactic efficacy of Trametin is confirmed by an increase in phagocytic activity by 10.5%, phagocytic index by 61.8%, and phagocytic number by 52.8%. After Trametin administration, the bactericidal activity of the serum increases by 60%. Cycloferon exhibits a similar immunostimulatory effect. Nonspecific prophylaxis using Trametin is shown to reduce the incidence of bacterial and viral respiratory diseases in young calves and generally improve their immunity.

Evaluation of toxicological profile of methanol leaf extract of Waltheria indica (Sterculiaceae)

Waltheria indica has been claimed to be used in managing several diseases in traditional medicine, although substantial scientific data are not available as regards its safety despite its pronounced efficacy in management of some ailments. Therefore, methanol leaf extract of W. indica was evaluated for its effects on some toxicological parameters using experimental animals. However, acute and sub-acute toxicity were carried out using experimental animals as described by standard methods. Absence of death reported after 24 hours of single oral administration of W. indica indicated that the crude drug is safe orally and the sample also had no effect on both hematological and biochemical parameters, with mild toxicity observed with some vital enzymes and organs upon continuous oral administration of W. indica for 21 days. However, it can be concluded that prolong usage of the plant for disease management should be discouraged, which implies that usage of the pant for short time usage in disease management.

Study of the pharmacokinetics of various drugs under conditions of antiorthostatic hypokinesia and the pharmacokinetics of acetaminophen under long-term spaceflight conditions

Objectives To study the pharmacokinetics and relative bioavailability of drugs of different chemical structure and pharmacological action under conditions simulating the effects of some factors of spaceflight, as well as the peculiarities of the pharmacokinetics of acetaminophen under long-term spaceflight conditions. Methods The pharmacokinetics of verapamil (n=8), propranolol (n=8), etacizine (n=9), furosemide (n=6), and acetaminophen (n=7) in healthy volunteers after a single oral administration under normal conditions (background) and under antiorthostatic hypokinesia (ANOH), the pharmacokinetics of acetaminophen in spaceflight members under normal ground conditions (background) (n=8) and under prolonged spaceflight conditions (SF) (n=5) were studied. Results The stay of volunteers under antiorthostatic hypokinesia had different effects on the pharmacokinetics and bioavailability of drugs: Compared to background, there was a decreasing trend in Vz for verapamil (−54 Δ%), furosemide (−20 Δ%), propranolol (−8 Δ%), and acetaminophen (−9 Δ%), but a statistically significant increase in Vz was found for etacizine (+39 Δ%); there was an increasing trend in Clt for propranolol (+13 Δ%) and acetaminophen (+16 Δ%), and a decreasing trend in Clt for etacizine, verapamil, and furosemide (−22, −23 and −9 Δ% respectively) in ANOH. The relative bioavailability of etacizine, verapamil, and furosemide in ANOH increased compared to background (+40, +23 and +13 Δ%, respectively), propranolol and acetaminophen decreased (−5 and −12 Δ% accordingly). The relative rate of absorption of etacizine and furosemide in ANOH decreased (−19 and −20 Δ%, respectively) while that of verapamil, propranolol, and acetaminophen increased (+42, +58 and +26 Δ%, respectively). A statistically significant decrease in AUC0-∞ (−57 Δ%), Cmax (−53 Δ%), relative bioavailability of acetaminophen (−52 Δ%) and a sharp increase in Clt (+147 Δ%), Tmax (+131 Δ%) as well as a trend towards a significant decrease in T1/2 (−53 Δ%), MRT (−36 Δ%) and a moderate increase in Vz (+24 Δ%) were found under control compared to background. Unidirectional changes in AUC0-∞, Clt, T1/2, MRT and relative bioavailability of acetaminophen, which are more pronounced in SF and opposite dynamics for Cmax, Tmax, Vz were found in ANOH and SP compared to background studies. Conclusions The data obtained allow recommending the studied drugs for rational pharmacotherapy in the possible development of cardiovascular disease in manned spaceflight.

Evaluation of Antidiarrheal Activity of 80% Methanolic Extract of the Leaves of Cordia africana (Lamiaceae) in Mice

Background. Diarrheal disease is a major cause of morbidity and mortality throughout the world, particularly in developing countries. Currently available drugs are linked with adverse effects, contraindications, and risk of resistance. Traditionally, the leaf concoction of Cordia africana is claimed to be used for diarrhea. However, the safety and efficacy of the leaf extract have not been scientifically approved yet. Therefore, the study was conducted to validate its antidiarrheal activity and safety profile in mice. Method. The hydromethanolic extract was obtained by the cold maceration technique in 80% methanol. Phytochemical screening tests were done for secondary metabolites by using standard tests. The antidiarrheal activity of the test extract at the doses of 100, 200, and 400 mg/kg was evaluated by using castor oil-induced diarrheal, gastrointestinal transit, and enteropooling models in mice. Result. In an acute toxicity study, there were no visible signs of toxicity and mortality following a single oral administration of 2000 mg/kg. Phytochemical screening tests revealed the presence of alkaloids, saponins, flavonoids, terpenoids, phenols, and tannins. The hydromethanolic extract significantly prolonged the onset of diarrhea and reduced the weight of wet and total feces at 100 ( P < 0.01 ), 200 ( P < 0.001 ), and 400 mg/kg ( P < 0.001 ) in the castor oil-induced diarrheal model. However, in the gastrointestinal transit model, a significant ( P < 0.001 ) reduction in the charcoal meal travel was observed in the middle (200 mg/kg) and higher (400 mg/kg) test doses. Similarly, the extract produced a significant ( P < 0.001 ) reduction in the weight and volume of intestinal contents at the aforementioned doses. Conclusion. The study demonstrated that the test extract showed promising antidiarrheal activity. Hence, this study supports its antidiarrheal use in Ethiopian folklore medicine.

Beneficial Effects of Slow-Release Large Neutral Amino Acids after a Phenylalanine Oral Load in Patients with Phenylketonuria

The mainstay of phenylketonuria treatment is a low protein diet, supplemented with phenylalanine (Phe)-free protein substitutes and micronutrients. Adhering to this diet is challenging, and even patients with good metabolic control who follow the dietary prescriptions in everyday life ignore the recommendations occasionally. The present study explores the ability of slow-release large neutral amino acids (srLNAAs) to prevent Phe increase following a Phe dietary load. Fourteen phenylketonuric patients aged ≥13 years were enrolled in a 6-week protocol. Oral acute Phe loads of 250 and 500 mg were added to the evening meal together with srLNAAs (0.5 gr/kg). Phe and tyrosine were dosed before dinner, 2h-after dinner, and after the overnight fast. After oral Phe loads, mean plasma Phe remained stable and below 600 µmol/L. No Phe peaks were registered. Tyrosine levels significantly increased, and Phe/Tyrosine ratio decreased. No adverse events were registered. In conclusion, a single oral administration of srLNAAs at the dose of 0.5 gr/kg is effective in maintaining stable plasma Phe during acute oral loads with Phe-containing food and may be added to the dietetic scheme in situations in which patients with generally good adherence to diet foresee a higher than prescribed Phe intake due to their commitments.

Lyme disease: Modern approaches to prevention, diagnosis and treatment

Lyme disease (LD) or tick-borne borreliosis affects thousands of people every year in different regions of the world, primarily the United States and Europe. In endemic areas, early LD is a common disease that requires high medical vigilance. Considering the extreme relevance of this problem for public health, in November 2020, the committee of experts of three American scientific societies published an updated version of the clinical guidelines for the prevention, diagnosis and treatment of LD, the main provisions of which are presented in this article. It is emphasized that in the absence of vaccines, the risk of LD and other diseases transmitted by ticks can be reduced by using personal protective equipment and repellents. Antibiotic prophylaxis is carried out by a single oral administration of doxycycline. In the laboratory diagnosis of LD, the determination of antibodies to B. burgdorfery in the blood serum is a first-line study. At the second stage, serum samples are examined using an immunoblot for IgM and IgG. The basis of treatment of LD is rational antibiotic therapy. The choice of an antibiotic depends on a number of factors, including the presence of extracutaneous manifestations of LD (neuroborreliosis, carditis, arthritis). The most commonly used are doxycycline, amoxicillin, cefuroxime-axetil and ceftriaxone.

Inhibition of serotonergic signaling induces higher consumption of both sucrose solution and toxic baits in carpenter ants

Biogenic amines play an important role in the regulation of appetitive responses in insects. Among them, serotonin (5-HT) regulates feeding-related processes in numerous insect species. In carpenter ants, 5-HT administration has been shown to depress feeding behavior, thus opening the possibility of using 5-HT modulation in control strategies against those species considered as pest. Here we studied if administration of a 5-HT antagonist, ketanserin, promotes feeding of a sucrose solution and a toxic bait in carpenter ants Camponotus mus. We found that 3 h after a single oral administration of ketanserin, the mass of sucrose solution consumed by carpenter ants increased significantly. A similar effect was found after a chronic administration that lasted 5 days. Yet, ketanserin did neither affect the intake rates nor the activity of the pharyngeal pump that mediates feeding dynamics. In addition, ketanserin promoted the consumption of a toxic bait based on boric acid. Our results thus show that feeding motivation and consumption of both sucrose solution and a toxic bait can be enhanced via prior administration of ketanserin. We discuss the possible mechanisms underlying these effects and conclude that understanding basic physiological and neural principles that underlie feeding motivation allows establishing more efficient control strategies for pest insects.

Study of Antiulcer activity of a hydrogel based on chitosan

In this study, the antiulcer activity of a gel based on high-viscosity chitosan was studied in models of NSAID and ethanol-induced ulcerogenesis. To simulate damage to the gastric mucosa in the NSAID model, diclofenac sodium was administered to experimental animals at a dose of 50mg/kg. An antiseptic intestinal and astringent agent was chosen as reference drug: bismuth tripotassium dicitrate at a dose of 0.017g/kg. The studied gel was used in 3 doses (0.08, 0.16 and 0.24ml/100g of body weight). In ethanol model, ulcers were induced by a single administration of ethanol 96% at a dose of 5ml/kg. Omeprazole at a dose of 20mg/kg was used as reference drug in this model. Chitosan-based gel was administrated in this model at a dose of 0.16ml per 100g of animals, which corresponds to the minimum available dose with antiulcer activity in the NSAID model. All investigated substances were injected intragastrically using a gastric tube. As a result of this research, it was found that the chitosan-based gel is effective in the NSAID gastropathy model but not effective in the ethanol model. In the NSAID gastropathy model, after a single oral administration of chitosan-based gel at doses of 0.16 and 0.24ml/ 100g, sufficient antiulcer activity was revealed, which was 2.4 and 4.694, respectively, and exceeded the effect of the reference drug, bismuth tripotassium dicitrate. In the ethanol model, the results of experimental studies showed that the reference drug, omeprazole, provides antiulcer activity with a calculated value of the antiulcer activity index of 2.18. After the administration of a chitosan-based gel at a dose of 0.16 ml per 100g of body weight of animals, compared with the control, the calculated value of antiulcer activity was 1.18, which characterizes the absence of an antiulcer effect.