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Biomedical subjects

D Maysinger

Publications and source records attributed to D Maysinger.

90 records · Page 5Linked to original sources
PubMed1980

Biologically active Mannich bases derived from nitroxoline.

A series of compounds with various basic side chains were derived from 5-nitro-8-hydroxyquinoline (nitroxoline). Aminomethylation of nitroxoline led exclusively to the formation of o-substituted phenolic Mannich bases. Depending on the kind of the primary or secondary amine participating in the Mannich reaction differently substituted compounds were prepared in order to study the influence of the basic side chain on their biological activity. The compound with N-bis(2-hydroxyethyl)amino group exhibited the highest mitodepressant activity determined in a phyto test on Lepidium sativum L. Preliminary test for antibacterial and antifungal activities using standard test microorganisms indicate rather strong antimicrobial properties of several synthesized compounds.

Amines↗
PubMed1980

Antibacterial and antifungal activities of nitroxoline Mannich bases.

The in vitro activity of nitroxoline and its Mannich bases against bacteria and fungi was investigated. Nitroxoline and its derivative with diisopropylamine as an amino component, exhibited the highest antimicrobial activity. The optimum hydro/lipophilic properties (log P), both for antibacterial and antifungal activity, are about log P values of 2. The least effective compound was this nitroxoline Mannich base which has diethanolamine as an amino component.

Amines↗
PubMed1980

Effects of isatin N-Mannich bases on HeLa cells.

A congeneric series of 5-haloisatins was synthesised and tested for biological activity. Mannich bases and hydrazones of 5-chloro- and 5-iodoisatin were prepared and their structures were determined spectrophotometrically. Morphological deformations and inhibition of radiolabelled precursor incorporation into DNA were studied in HeLa cell culture; antimitotic activity was examined using a phyto test with Lepidium sativum L. I50 values were determined for the most interesting compounds. The results obtained can be interpreted in terms of the group contributions to the parent molecule. Introduction of iodine into the aromatic moiety of isatin (position 5) considerably increased inhibitory potency of the parent molecule. Furthermore, N-bis-(2-chloroethyl) and N-bis-(2-hydroxyethyl) groups, respectively, as amino components of some of the N-Mannich bases, markedly enhance the biological activities studied in this work.

Amines↗
PubMed1980

Structure-activity relationship of isatin Mannich bases and hydrazones.

35 isatin Mannich bases and hydrazones were tested fore their mitodepressant activity applying a phyto test with Lepidium sativum L. The obtained results were subjected to the Free-Wilson's analysis. Although calculated and experimentally determined mitodepressant activities differ considerably in some cases, there is a correlation (r = 0.94) between the studied structures and mitodepressant activities.

Amines↗
PubMed1980

Structural analogues of isatin and their antimicrobial activity.

A series of 5-haloisatins were aminomethylated in position 1 and hydrazino groups were introduced in position 3. Synthesized N-Mannich bases and hydrazones were biologically tested against various kinds of bacteria and fungi. Results from these in vitro studies showed a considerable growth inhibition of some gram negative bacteria caused by chlorinated N-Mannich bases of isatin. Comparing the inhibition zones of the halogenated isatin N-Mannich bases with structural analogues of nonhalogenated ones as well as with isatin itself, an increase in antimicrobial activity was observed, thus, indicating the importance of both substituents, namely, halogen in position 5 and an amino moiety in position 1. The most biologically active compound was found to be diisopropylamino-N-Mannich base of 5-chloroisatin.

Anti-Bacterial Agents↗
PubMed1979

Antibacterial and antifungal activities of isatin N-Mannich bases.

The antimicrobial and antifungal activities of 29 congeneric isatin N-Mannich bases were investigated by testing against standard test microorganisms and 21 pathogenic Gram-negative microorganisms. Considerable growth inhibition of Gram-negative bacteria and yeasts and slight inhibition of Gram-positive bacteria resulted when they were treated with the various N-Mannich bases of isatin and 5-nitroisatin, respectively.

Anti-Bacterial Agents↗
PubMed1979

[Biologically active azomethines. Delépine reaction with 1-chloromethylisatin; preparation of some 1-aminomethylisatinazomethines (author's transl)].

The authors describe the synthesis of I-aminomethylisatin (3) from [I-chloromethylisatin] (1) by means of the Delépine reaction. On condensation with aromatic aldehydes, 3 yields the azomethines 5--7. The azomethine 5 is converted into the corresponding thiosemicarbazone 9. Testing for mitodepressive activity showed that the compounds 5--7 are active. On testing in vitro for tuberculostatic effects, the compound 9 proved exceptionally potent.

Antitubercular Agents↗
PubMed1979

[Biologically active N-Mannich bases of isatin-3-(phenyl)-imines (author's transl)].

By the condensation of isatin and 5-nitroisatin with substituted aromatic amines, isatin- and 5-nitroisatin-3-(phenyl)-imines (azomethines) are formed which are converted into N-Mannich-bases by aminomethylation and may be formulated as azomethines with E configuration. A biotest of Lepidium sativum L. was used to prove mitodepressive properties. Some compounds showed a significant growth-inhibiting activity. It was found that a change in activity is produced by condensation on the carbon atom in position 3 and by aminomethylation on the nitrogen atom in the isatin nucleus.

Imines↗
PubMed1977

Preparation and high-performance liquid chromatography of iodinated diethylstilbestrols and some related steroids.

Diethylstilbestrol and estradiol have been converted to their mono- and poly-iodinated derivatives by electrophilic substitution of positive iodine into the activated aromatic rings. Both chemical and electrochemical procedures have been employed for the iodination, and the latter procedure proved to be superior. These iodinated derivatives have been purified by preparative high-performance liquid chromatography, and characterized by ultraviolet and mass spectroscopy.

Chemical Phenomena↗
PubMedDate not supplied

The hematopoietic cytokine, colony-stimulating factor 1, is also a growth factor in the CNS: congenital absence of CSF-1 in mice results in abnormal microglial response and increased neuron vulnerability to injury.

In this study we used op/op mice, which are deficient in the hematopoietic cytokine, colony-stimulating factor 1 (CSF-1), to determine the effect of CSF-1 on neuronal survival and microglial response in injury. In normal mice microglia express the CSF-1 receptor and are primarily regulated by CSF-1, produced mainly by astrocytes. The CSF-1 deficiency in op/op mice results in a depletion in the number of monocytes and macrophages but does not affect the number or morphology of microglia. We produced an ischemic lesion in the cerebral cortex of mice by disrupting the pia-arachnoid blood vessels in a defined area. Using Nissl stain and astrocyte- and microglia-specific antibodies, we determined the number of viable neurons in such injury and the intensity of glial reaction. The cellular response to injury on the operated side of op/op mice was compared to that on the non-operated contralateral side and to the cellular response in similar lesions in CSF-1 producing C3H/HeJ mice. We found that the systemic lack of CSF-1 in op/op mice results in a significant increase in neuron vulnerability to ischemic injury and considerably reduced microglial response to neuron injury. Remedying the CSF-1 deficiency, either by grafting CSF-1 secreting astroglia into the brain or by implanting encapsulated CSF-1 secreting fibroblast-like cells into the peritoneum, partially restores the microglial response to neuron injury and significantly potentiates neuronal survival in cerebral cortex ischemic lesions. Astroglial reaction was approximately the same in the lesions in op/op mice, grafted and implanted op/op mice and C3H/HeJ mice, indicating that CSF-1 modulates microglia, but not the response of astrocytes to injury. The degree of neuronal survival was not correlated to the degree of microglial proliferation and intensity of their reaction. We report some indications that CSF-1, in addition to modulation of microglia, may also act directly on neurons.

Animals↗
PubMedDate not supplied

Perspectives on reproductive senescence and biological aging: studies in genetically altered follitropin receptor knockout [FORKO] mice.

Increased life expectancy leads to increased age-associated health issues in both sexes. For menopausal women the most important of these appear to result from the severe estrogen deficiency caused by ovarian dysfunction. The consequences among others include hot flashes, osteoporosis, obesity, impaired memory, higher incidence of Alzheimer's disease and cardiovascular disease. Ovarian function and steroidogenesis are influenced by pituitary gonadotropins, including follicle-stimulating hormone (FSH), whose actions are mediated through ovarian receptors. This article highlights our recent data pertinent to aging as derived from a novel genetically modified animal model [the FORKO mouse (FOllitropin Receptor KnockOut) lacking the FSH receptor. FORKO female mice experience a chronic depletion of estrogen (E2) from early development, and have phenotypes similar to aging women, with ovarian failure, obesity, skeletal changes, and ovarian tumors. A variety of findings support the conclusion that E2 deficiency in FORKO mice is responsible for their neural impairments associated with glial cell hypertrophy, region-specific brain cells loss, and abnormal behavior. Findings from mice with FSH receptor haploinsufficiency mice ('menopausal mice') are also shedding light on the molecular basis of menopausal conditions that include degeneration of the hippocampus. Many phenotypes noted in the null condition also occur in +/- females but in an age related manner. Thus, the FORKO mouse becomes an excellent model to investigate mechanisms underlying age-related changes especially when these events are accelerated, as in menopausal women. Opportunities abound to assess the potential benefits/adverse effects of hormone replacement regimen on various targets.

Aging↗
PubMedDate not supplied

Polycaprolactone-b-poly(ethylene oxide) block copolymer micelles as a novel drug delivery vehicle for neurotrophic agents FK506 and L-685,818.

Micelles formed from polycaprolactone-b-poly(ethylene oxide) (PCL-b-PEO) diblock copolymers were investigated as a novel drug delivery system. The affinity of the micelles for hydrophobic solubilizates was assayed by determining the partition coefficient for the lipophilic compound, pyrene, between the micelles and water; the partition coefficient was found to be on the order of 10(2). The Trypan blue and Alamar blue survival assays were used to assess the in vitro biocompatibility of the micelles with PC 12 cells, MCF-7 breast cancer cells, and primary cultures of human microglia, astrocytes, and cortical neurons. The micelles were then studied as a delivery vehicle for the neurotrophic agents FK506 and L-685,818 in PC 12 cell cultures. In both cases, the micelle-incorporated drugs, in the presence of nerve growth factor (5 ng/mL), were able to promote the degree of differentiation of the PC 12 rat pheochromocytoma cells.

Animals↗
PubMedDate not supplied

PCL-b-PEO micelles as a delivery vehicle for FK506: assessment of a functional recovery of crushed peripheral nerve.

The aim of this work was to test in vivo a new block copolymer-based delivery system containing lipophilic drug FK506, known as Tacrolimus. Tacrolimus is currently used in clinics as an immunosupressant agent, and more recently it has been shown that it can exert neurotrophic effects. We prepared, characterized, and assessed polycaprolactone-b-polyethylenoxyde (PCL-b-PEO) micelles containing FK506 in vitro and in vivo. By using well-established animal model of peripheral nerve injury (crushed sciatic nerve), we show that the rate of functional recovery of injured nerve is significantly enhanced in rats treated with micellar FK506. These findings support the notion that PCL-b-PEO is a suitable polymer material for FK506 and suggest its wider applicability as a delivery vehicle for other biologically active, poorly soluble therapeutic agents.

Animals↗
PubMedDate not supplied

Microencapsulation and the grafting of genetically transformed cells as therapeutic strategies to rescue degenerating neurons of the CNS.

A number of approaches have been developed to deliver growth factors within the central nervous system of adult mammals. Initially a variety of neurotrophic factors were administered either by single intracerebroventricular or local injections directly into brain tissues or via permanently installed cannulae for chronic administrations. More recently delivery systems including conjugates, biodegradable and non-biodegradable implants and microspheres as well as genetically engineered cells have been introduced in order to provide a prolonged supply of neurotrophic factors and to prevent their enzymatic degradation. In this review we examine a variety of means of delivering neurotrophic factors (mainly nerve growth factor) with the primary focus upon the use of microencapsulated neurotrophins and cells genetically modified to produce them. In addition, this review highlights some difficulties and future trends in the development of novel delivery systems hopefully more suitable for investigations in different areas of neuroscience.

Animals↗
PubMedDate not supplied

Microencapsulated monosialoganglioside GM1: physical properties and in vivo effects.

The prevention of the decrease of choline acetyltransferase (ChAT) enzymatic activity was achieved by applying GM1 in an animal model for studying retrograde degenerations of cholinergic neurons. Devascularizing lesions of the rat cortex led to a significant decrease in activity of ChAT in the nucleus basalis magnocellularis (NBM), but this decrease was effectively prevented by GM1 administration either centrally or locally in a microencapsulated form. Compared with the relatively large dose of GM1 which has to be given when the drug is administered. i.p. microencapsulated GM1 applied locally and directly over the lesioned cortical surface seems to be effective in much lower doses.

Animals↗
PubMedDate not supplied

Microparticles with neuroactive agents.

An overview of biodegradable and biocompatible microcapsules and microspheres loaded with neuroactive substances, or cells producing neuroactive substances, and their role as drug delivery systems (DDS) for drug administration to the central nervous system (CNS) is given. In addition, closely related systems are also summarized.

Animals↗