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Biomedical subjects

J Lachowicz

Publications and source records attributed to J Lachowicz.

13 recordsLinked to original sources
PubMed2001

Muscarinic agonists and antagonists in the treatment of Alzheimer's disease.

Alzheimer's disease (AD) is a neurodegenerative disease characterized by cognitive impairment and personality changes. The development of drugs for the treatment of the cognitive deficits of AD has focused on agents which counteract loss in cholinergic activity. Although symptoms of AD have been successfully treated with acetylcholinesterase inhibitors (tacrine, donepezil. rivastigmine, galanthamine), limited success has been achieved with direct M1 agonists, probably due to their lack of selectivity versus other muscarinic receptor subtypes. Muscarinic M2 antagonists have been reported to increase synaptic levels of acetylcholine after oral administration to rats (e.g. BIBN-99, SCH-57790), but their selectivity versus other muscarinic receptor subtypes is modest. Exploration of a series of piperidinylpiperidines has yielded the potent and selective M2 antagonist SCH-217443. This antagonist has excellent bioavailability in rats and dogs and shows activity in a rat model of cognition.

Alzheimer Disease↗
PubMed2001

[Infection of red deer with lung nematodes in Polish and Belorussian parts of Białowieza Forest].

Fecal samples from red deer from polish and belorussian parts of Białowieza Forest were examined by Baermann method. First stage larvae of three species of lung nematodes were found. In polish part in 100% of samples were larvae of E. cervi, in 50% V. sagittatus and in 21% D. noerneri, and in belorussian the level of infection was lower and larvae were in 92%, 36% and 12% of samples respectively. In significant part of samples were met mixtured invasion of two or three species. Finding of larvae of E. cervi is the first registration of this species in belorussian part of Białowieza Forest, and V. sagittatus is a new species for the fauna of Byelorussia. Nematodes E. cervi are dangerous for domestic ruminants.

Animals↗
PubMed2000

ADP is the cognate ligand for the orphan G protein-coupled receptor SP1999.

P2Y receptors are a class of G protein-coupled receptors activated primarily by ATP, UTP, and UDP. Five mammalian P2Y receptors have been cloned so far including P2Y1, P2Y2, P2Y4, P2Y6, and P2Y11. P2Y1, P2Y2, and P2Y6 couple to the activation of phospholipase C, whereas P2Y4 and P2Y11 couple to the activation of both phospholipase C and the adenylyl cyclase pathways. Additional ADP receptors linked to Galpha(i) have been described but have not yet been cloned. SP1999 is an orphan G protein-coupled receptor, which is highly expressed in brain, spinal cord, and blood platelets. In the present study, we demonstrate that SP1999 is a Galpha(i)-coupled receptor that is potently activated by ADP. In an effort to identify ligands for SP1999, fractionated rat spinal cord extracts were assayed for Ca(2+) mobilization activity against Chinese hamster ovary cells transiently transfected with SP1999 and chimeric Galpha subunits (Galpha(q/i)). A substance that selectively activated SP1999-transfected cells was identified and purified through a series of chromatographic steps. Mass spectral analysis of the purified material definitively identified it as ADP. ADP was subsequently shown to inhibit forskolin-stimulated adenylyl cyclase activity through selective activation of SP1999 with an EC(50) of 60 nM. Other nucleotides were able to activate SP1999 with a rank order of potency 2-MeS-ATP = 2-MeS-ADP > ADP = adenosine 5'-O-2-(thio)diphosphate > 2-Cl-ATP > adenosine 5'-O-(thiotriphosphate). Thus, SP1999 is a novel, Galpha(i)-linked receptor for ADP.

3T3 Cells↗
PubMed2000

Diphenylsulfone muscarinic antagonists: piperidine derivatives with high M2 selectivity and improved potency.

Piperidine analogues of our previously described piperazine muscarinic antagonists are described. Piperidine analogues show a distinct structure-activity relationship (SAR) that differs from comparable piperazines. Compounds with high selectivity and improved potency for the M2 receptor have been identified. The lead compound, 12b, increases acetylcholine release in vivo. Compounds of this class may be useful for the treatment of cognitive disorders such as Alzheimer's disease (AD).

Acetylcholine↗
PubMed2000

[Travassosius rufus (Trichostrongylidae)--new for Poland nematode of beavers and comments about helminthfauna of these animals].

Two females of beaver from north-east Poland were necropsied. Moreover, 15 samples of feaces were examinated. Both necropsied beavers were infected with 46 and 362 specimens of trematode Stichorchis subtriquetrus (RUDOLPHI 1814). In stomach of one beaver were found 2800 specimens of nematode Travassosius rufus Khalil, 1922. It was the first registration of this species in Poland. Coproscopical examination showed eggs of S. subtriquetrus in all 15 fecal samples and eggs T. rufus in 5 samples.

Animals↗
PubMed2000

[Helminth fauna of free living European bison Bison bonasus (L.) in Bieszczady Mountains (Karpatian Mountains, Poland)].

Four free living European bison from Białowieza/Caucasus line shot in February 1997 within Lutowiska Forestry District in the Bieszczady Mountains were used in investigations. All examined animals were infected with helminths. There were found 10 species of parasites. Five species of them Ostertagia leptospicularis, O. kolchida, Spiculopteragia boehmi, Cooperia pectinata and Ashworthius sidemi are thypical parasites of Cervides, and from them were infected bison in Bieszczady. In all necropsied animals was found invasion of nematode A. sidemi, with mean intensity 1542 specimens. It is the first registration of A. sidemi in Poland and European bison is a new host for this parasite. It seems that the source of infection A. sidemi in European bison in Bieszczady is the local population of deer, which during their migrations could bring this parasite from neighbouring Ukraine and Slovakia, where this nematode have been introduced together with deer Cervus nippon. There are also presented results of coproscopic examinations of 17 fecal samples from free living European bison in Bieszczady.

Adaptation, Biological↗
PubMed1999

[Attempt of deworming of red and fallow deer in deer farm with rintal premix].

Rintal 2.4% premix (Bayer) in single dose 7.5 mg of active substance on kg body weight was given to the calves of red and fallow deer. Effectiveness of deworming against nematodes from family Trichostrongylidae was 85.2% in red and 97.8% in fallow deer. Against namatodes from genus Trichocephalus the effectiveness was higher extending in red deer 98.1%, and in fallow deer 99.5%. Anthelmintic was not effective against nematodes Varestrongylus sagittatus and Elaphostrongylus cervi.

Animals↗
PubMed1990

[Large-intestinal nematoda in bison].

In the Białowieza Forest the parasitological autopsy of large intestine of 6 bisons was made at the beginning of winter of 1987-1988, and 9 dissections were made in the latter part of both seasons. Four species of nematodes were found to occur together: Chabertia ovina, Oesophagostomum radiatum, Oe. venulosum and Trichocephalus ovis. At the end of wintering in bisons the invasion of Ch. ovina appeared in high percent of animals, but the intensity of it was low. However, the extensity and intensity of invasion of three remaining species of nematodes distinctly arose. In comparison with bisons in closed reserves, free living bisons assimilated Oe. venulosum and Ch. ovina. It is likely that the winter quarters are the source of invasion. It can be explained by the permanent accumulation of feaces with invasive forms of nematodes, and by feeding bisons on the great amount of hay, in which the invasive forms of nematodes may also occur.

Animals↗
PubMed1989

[Harboring of helminth parasites by the European bison (Bison bonasus L.) and deer (Cervidae) in the Białowieza forest].

Parasitological autopsy of 31 european bison , 9 red-deer and 3 roe-deer was made in Białowieza Forest in the period 1983-1988. Together 20 species of nematodes were found, from them as much as 18 in bison , 6 in red-deer and 8 in roe-deer . The highest intensity and 100% of extensity was shown by nematodes from subfamily Ostertagiinae. Four species of this subfamily (O. leptospicularis, O. kolchida, S. boehmi i S. mathevossiani) have been permanently adapted by bison from cervids, however two species of nematodes typical for bison and cattle (O. ostertagii and O. lyrata) have not been adopted by deer . Besides, bison adopted from deer the following species of nematodes: T. capricola, C. pectinata, N. roscidus, N. europaeus and from moose N. alcidis. Bison gave to red-deer only C. bilobata, and roe-deer have not adopted any nematodes from bison . B. trigonocephalum and S. dagestanica found in roe-deer are in Poland typical parasites of moose .

Adaptation, Biological↗
PubMed1988

Effects of prenatal dexamethasone on development of ornithine decarboxylase activity in brain and peripheral tissues of rats.

The use of glucocorticoids in the management of neonatal respiratory distress syndrome may be associated with abnormalities of growth and neurologic development. In our study, pregnant rats received either 2 or 0.2 mg/kg of dexamethasone on gestational days 17, 18, and 19 and tissues of the offspring were examined for ornithine decarboxylase activity, a marker enzyme for perturbations of cellular maturation. Acutely, the higher dose of dexamethasone suppressed ornithine decarboxylase activity in all tissues except lung, where a short-term stimulation was obtained. Repeated administration of 2 mg/kg resulted in an ornithine decarboxylase pattern consistent with delayed cellular development in all tissues (suppressed activity followed by prolonged postnatal elevations), accompanied by impaired viability and general growth. Lowering the dose of dexamethasone to 0.2 mg/kg eliminated all the adverse effects on viability but still produced perturbations of tissue ornithine decarboxylase, most notably a prolonged suppression of activity across all brain regions. These data suggest that administration of glucocorticoids even at the threshold for effects on respiratory function, may compromise neural development.

Animals↗
PubMed1980

The rate of absorption of synthetic lysine and dietary protein in the upper half of the small intestine of pigs.

The aim of the present work was to estimate the rate of lysine absorption in the upper part of the small intestine as related to the absorption of total nitrogen and other amino acids in pigs given feed (barley + sesame meal) supplemented with lysine and fed once or 4 times daily. The experiments were carried out on 6 pigs fitted with reentrant cannulas sited in 3 of them about 4 m and in an other 3 about 9 m distal to the pylorus (mean intestine length was about 18 m). The frequency of feeding influenced the rate of flow of total nitrogen and lysine through the intestine. The content of lysine in the digesta (g/16 g N) during the first 5 hours after morning feeding, and particularly between 8.00-10.00 h, was much higher with once daily than with four times daily feeding while during the subsequent 15 hours the reverse was true. The absorption of lysine occurred at a faster rate than that of the other amino acids and was closest to that of arginine and methionine. On the whole, the net absorption rate of essential amino acids in the upper part of the intestine of pigs was as follows: Lys, Met greater than His, Phe, Leu greater than Trp, Ile, Val greater than Thr (Cys). It seems that the more uniform passage through and absorption from the alimentary tract of synethetic lysine and dietary protein, observed at frequent feeding could contribute to their better utilization for protein synthesis in the organism.

Animals↗