[Study of structure-activity relationship in series of Gsb-106 analogues-dipeptide mimetics of brain-derived neurotrophic factor].

In previous work we have obtained a dimeric dipeptide mimetic of 4th loop of BDNF - hexamethylenediamide bis-(N-monosuccinil-L-seryl-L-lysine) (GSB-106), having a neuroprotective activity in vitro in a concentration range 10(-5)-10(-8) M and an antidepressant activity in vivo at doses 0.1 and 1 mg/kg i.p. in rats. We have investigated the structural and functional relationships among analogues of GSB-106. Glycine scan was performed and a number of appropriate compounds were synthesized: GT-105 (here lysine is replaced by glycine), GT-107 (here serine is replaced by glycine), GT-106Ac (here monosuccinic radical is replaced by acetyl group). We have studied the dependence of activity of following compounds from the configuration of amino acid residues: GT-107D (D-enantiomer of the GT-107), GT-106DL (L-serine was replaced by D-serine), GT-106LD (L-lysine was replaced by D-lysine). The investigation of these compounds using the HT22 cell culture in conditions of oxidative stress has approved only two analogues of GSB-106 to have a neuroprotective effect: in the case of replacement of serine to glycine and of replacment of succinic radical to acetic group. A disappearance of this effect was observed in event of the replacement of lysine residue to glycine in GT-105, L-lysine residue to D-lysine and also by conversion of serine configuration. These results show that lysine residue is crucial for the neuroprotective activity of GSB-106. L-Configuration of the lysine and serine residues required. Configuration of lysine residue becomes critical in absence of serine side group. Thus, the the following fragment is a minimum pharmacophore of beta-turn of 4 loop of BDNF: HOOC-CH2-CH-CO-NH-(S)-CH(CH2OH)-CO-NH-(S)-CH((CH2)4NHz)-CO-NH-(CH2)3-. Only one (GT-106Ac) out of two analogues of GSB-106 with neuroprotective activity possesses antidepressant activity too. This fact indicates about a necessity of more stringent structural requirements for exposure of antidepressant activity. The results obtained can be useful for designing of new active mimetics of BDNE

[The epizootology and epidemiology of echinococcosis and paecilomycosis].

Fungi of the genus Paecilomyces, a causative agent of the fungal disease paecilomycosis, have been found in the blood of productive animals (sheep, cattle, pigs, goats) that are carriers of Echinococcus larvocysts. In the Republic of Uzbekistan, the echinococcosis affection of sheep, cattle, pigs, and goats continues to remain high. Domestic fowls (chickens, turkeys, and gooses) have been established to be blood carriers of Paecilomyces fungi, which is also true for wild birds, such as my-lady's-belts, quails, chukars, and crows. The degree of fungal affection has been also established for birds.

[Study of the pathogenesis of paecilomycosis-complicated echinococcosis].

Experiments were carried out on 35 lambs infected with echinococcus eggs taken from canine donors, 5 lambs with echinococcosis, 5 lambs with echinococcosis + paecilomycosis, 5 lambs with coenurosis, 5 with cysticercosis ovis, 5 with alveococcosis, 5 with paecilomycosis, inoculated by the material taken from patients; and 5 healthy lambs formed a control group. Cystic hydatidosis was found to induce substantial cardiovascular changes.

[Procedure for Latrodectus reproduction in the laboratory setting and the preparation of the first Russian matrix from its venom to manufacture homeopathic remedies with antiparasitic activity].

The investigation was undertaken to study the biology and ecology of Latrodectus, the possibilities of its importation to Russia from other countries, to breed Latrodectus in the laboratory setting, and to design the first homeopathic matrix of Latrodectus to manufacture homeopathic remedies. The authors were the first to devise a method for Latrodectus breeding in the laboratory setting of Moscow and its vicinities. The Latrodectus bred in the laboratory is suitable to manufacture drugs and in captivity they do not lose its biological activity. The authors were the first to prepare a homeopathic Latrodectus matrix for homeopathic medicines, by using the new Russian extragent petroleum. Chromatography mass spectrometry was used to identify more than a hundred chemical compounds in the Russian petroleum. The biological activity of the petroleum Latrodectus matrix for the manufacture of homeopathic remedies was highly competitive with that of the traditional Latrodectus venom matrix made using ethyl alcohol. The homeopathic Latrodectus matrix made using glycerol lost its biological activity because of glycerol. The biological activity of homeopathic matrixes made from Latrodectus inhabiting the USA, Uzbekistan, and the south of Russia and from that bred in the laboratory was studied. The homeopathic matrix made from the Latrodectus living in the Samarkand Region, Republic of Uzbekistan, has the highest biological activity.

[The agent Latrodectus and canine paecilomycotic eclampsia as a laboratory model in the survey of treatment for mycoses and parasitic diseases].

The extragent used to prepare a Latrodectus mactans hydrocarbon extract is a multicomponent system composed of alkanes, alkenes, and arenes. More than 100 compounds were identified in the hydrocarbon extract (petroleum). The petroleum matrix of Latrodectus mactans was first obtained to manufacture homeopathic remedies. The authors could prepare the first Russian homeopathic medicine from Latrodectus mactans, which proved to be effective in treating canine eclampsia. Canine experiments provide a rationale for the authors' choice as the only homeopathic remedy among thousand known drugs to treat female eclampsia. It is Latrodectus mactans that is in the list of homeopathic medicines permitted for use in accordance with Order No. 335 (Supplement 2) of the Ministry of Health and Medical Industry of Russia, issued on November 29, 1995. It is manufactured from Latrodectus mactans living in the USA.

[Development of a new hydrocarbon extract from the medicinal raw material of Circassian walnut (Juglans regia) and study of its antiparasitic activity].

The authors developed a technology for preparing a hydrocarbon extract from the medicinal raw material of Circassian walnut (Juglans regia), including its green fruits, green leaves, and fresh roots. To prepare the preparation, they obtained for the first time a new extragent called petroleum Russia that was found to contain more than hundred chemical compounds by chromatography mass spectrometry. The new agent was named irillen. Experiments on albino mice and albino rats established that the new agent was low toxic. The lethal doses of irillen were calculated: LD50 was 16377 +/- 457.5 mg/kg; LD16 = 12986.4 mg/kg; LD84 was 18976.6 mg/kg for albino mice; LD50 was 16998.0 +/- 535.4 mg/kg; LD16 = 12875.3 mg/ kg; LD84 = 18583.4 mg/kg for albino rats. The irillen prepared by the authors should be referred to as a low toxic and practically nontoxic agent (Toxicity Class IV and V). Irillen has a broad spectrum of antiparasitic activity. It is effective in treating toxocariasis in dogs, larval alveolar echinococcosis, ascaridiasis, and eimeriasis in chickens, and siphachiasis.

[Amino acid exchange in paeci lomycosis-complicated echinococcosis].

The authors have detected atypical paecilomycosis-associated myocarditis with impaired amino acid exchange and pain syndrome for the first time. At first, pain occurs in the chest and radiates into the axilla, to the left arm to the finger tips, by paralyzing the arm. In some patients, pain manifests itself in both arms with radiation to the belly, by accompanying by fainting. The skin is wet, cold; the pulse is frequent and of poor volume and difficult-to-count. Heart pain spreads into the armpit and down the arm, by making the fingers numb. Attempts to use current analgesics (movalis, sirdalud, nimesil, morphine) in combination with fungicides (diflucan, mycosist, orungal) have failed to yield positive results. The homeopathic drug Latrodectus mactans, prepared from caracurt venom, in combination with the authors' designed diet and other homeopathic agents have relieved pain syndrome and normalized amino acid exchange, which offered possibilities for successful surgical treatment for echinococcosis with later recovery.