PubMed Health⌕ Search

Biomedical subjects

J Marx

Publications and source records attributed to J Marx.

At least 19 recordsLinked to original sources
PubMed2006

Cortisol resistance in conditions such as asthma and the involvement of 11beta-HSD-2: a hypothesis.

The two types of corticosteroid hormones, the mineralocorticoids and glucocorticoids, act in a complementary manner and are functionally closely linked. Aldosterone and glucocorticoids express their functions through the glucocorticoid receptors (GRs; GRalpha and GRbeta) and the mineralocorticoid receptors (MRs). Commercially available steroidal drugs used in conditions such as asthma may act on both GR and MR receptors; although glucocorticoid-receptor agonists play a fundamental role in the treatment of inflammatory conditions, prolonged exposure may have adverse effects such as the development of resistance. Glucocorticoid resistance in such conditions has been observed to be accompanied by a downregulation of GRalpha, a twofold decrease in GR protein half-life, downregulation of GRalpha mRNA expression, and enhanced expression of GRbeta. Other suggestions for glucocorticoid resistance include alternative splicing of the GR gene with subsequent expression of the GRbeta protein isoform, defective regulation of gene transcription of the GR gene or GR mutations, defective DNA binding and transactivating domains of the GR. In addition, we would like to suggest that dysregulation of the MR enzyme 11beta-HSD-2 may be one of the causes of resistance. When expressed in cells with MRs, this enzyme's major role is to prevent permanent occupancy of MR by glucocorticoid hormones, allowing concentration-dependent binding of aldosterone to MR. However, deficiency of the 11beta-HSD isoforms (particularly 11beta-HSD-2) leads to the activation of MRs by glucocorticoids rather than the glucocorticoids interacting with its "normal" receptors, the GRs. We will substantiate on support for our hypothesis in the dysregulation of this enzyme, which is typically associated with significantly higher levels of circulating plasma cortisol and elevated levels of cholesterol, little or no response to systemic glucocorticoids, and problems associated with homeostasis primarily in the distal nephron and distal colon. These are some of the symptoms typically noted in cortisol resistance.

11-beta-Hydroxysteroid Dehydrogenase Type 2↗
PubMed2006

Ultrastructural effects of low dosage endocrine disrupter chemicals on neural cells of the chicken embryo model.

Previous research suggests that endocrine disrupters (EDCs) like nonylphenol cause apoptosis (both via the intrinsic and extrinsic pathway) and that ROS generation and Ca (2+) play a fundamental role in the process. We have investigated morphological changes induced by 17beta-estradiol, nonylphenol, 17alpha-ethynylestradiol and diethylstilbestrol on the IN OVO neural chick embryo model by using transmission and scanning electron microscopy (TEM and SEM). We found that estrogenic substances such as nonylphenol, diethylstilbestrol (DES) and 17alpha-ethynylestradiol, as well as 17beta-estradiol cause ultrastructural changes to developing neurons, resulting in damage to the plasma, mitochondrial as well as nuclear membranes. Furthermore, both apoptotic blebbing and necrotic (or oncotic) budding was seen in TEM and SEM micrographs. SEM shows that nonylphenol-exposed neurons have irregular cell surfaces with pseudopodia, cell shrinkage and breakages in the plasma membrane--typical of apoptosis. TEM indicated that plasma membranes and double nuclear membranes have structural changes, with apoptotic bodies (blebbing) and disrupted mitochondrial membranes. In 17alpha-ethynylestradiol-exposed neurons, disruption of the plasma membrane with cell swelling and vacuolization was present. No apoptotic bodies or budding were noted here. 17beta-Estradiol induced openings in the plasma membrane, while DES-exposed neurons did not show any morphological changes. Therefore we conclude that EDC damage is morphologically visible and the damage is recognized as apoptosis and oncosis. Estrogenic substances may hence modify hormonal actions thereby leaving the developing nervous system more susceptible to damaging events.

Animals↗
PubMed2005

The neurotoxic effects of prenatal cardiac glycoside exposure: a hypothesis.

Cardiac glycosides (CGs) are beneficial in treating cardiac conditions; depending on time and dosage, they can also be toxic as they regularly cross the blood brain barrier and the placenta and may affect the unborn baby. This paper therefore focuses on the effects of CGs administered to the mother on normal cellular physiology of the foetus with specific reference to neural tissue. CGs act by binding to the Na+/K+-ATPase and decrease or inhibit Na+-K+ pump activity. In the foetus, CGs may disrupt ion homeostasis. An over-dosage of CGs or when it is taken during pregnancy, can also affect the neuro-energy levels of brain tissue in particular. We conclude and hypothesize that CGs in this case will not only cause severe alterations in neuronal function due to disruption of membrane activity, but also in glutamate clearance, affecting neurotransmission in general. Furthermore, elevated cytosolic Ca2+ will lead to permeabilization of the mitochondrial membranes, resulting ultimately in mitochondrial dysfunction. This will result in neurotoxicity--ensuing in neural cell damage or death, and we propose the mechanism to be due to neuro-necrapoptosis.

Animals↗
PubMed2005

Effects of Urginea sanguinea, a traditional asthma remedy, on embryo neuronal development.

The Southern African plant, Urginea sanguinea Shinz (Hyacinthaceae) (US), is a well-known traditional herbal medicine and it is used for many different ailments, including asthma. Pregnant women also use this plant and little is known regarding the toxic effects of this plant material on the developing foetus. US contains the cardiac glycoside (CG) Transvaalin; CGs are known to cross the placenta and blood-brain barrier and therefore may have a negative effect on the foetal development. To address this, in vitro cytotoxicity of this preparation as well as its effect on chick embryo neural development was investigated. Water extracts of US were shown to be cytotoxic in cell cultures of L929 cell and primary embryonic neural cell cultures. Electron microscopy studies following in ovo exposure revealed altered neuron morphology with patterns of cell damage either associated with apoptosis or necrosis. CGs are known to inhibit membrane bound Na(+)/K(+)-ATPase in conducting tissues, causing disruption of the calcium pathways, mitochondrial calcium overload leading to either apoptosis or necrosis or where both occur, a process of necrapoptosis. The in ovo effects observed strongly indicate that US causes necrapoptosis in chick embryonic neurons.

Animals↗
PubMed2004

Direct and indirect effects of corticosteroids on astrocyte function.

Corticosteroids are used for a variety of conditions; among the most well-known uses are for asthma and eczema. We review here the direct and indirect effects of corticosteroids on astrocyte physiology. Astrocytes play an important role in communication between neural cells, as one astrocyte can communicate with many neurons. They are also central in bringing nutrients through the blood-brain barrier (BBB) to the brain areas they serve. Therefore, any chemical or pharmaceutical product entering the brain via the BBB will first come into contact with the astrocytes. We discuss the direct effects that corticosteroids have on astrocyte physiology and functioning; these include inhibited glucose transport, decreased glycogen synthesis and decreased glutamate uptake. Furthermore, the indirect effects of corticosteroids on astrocytes are also reviewed. We know that corticosteroids lower neural serotonin. Lowered serotonin affects astrocyte functioning, and particularly astrocytic cAMP activities, a decrease in cytokine activities and impaired GABA uptake. These can be seen as the indirect effects of corticosteroids on astrocyte physiology. Corticosteroids therefore have a pertinent effect on neuro-energetics due to astrocyte physiology impairment, and this may ultimately be the reason for memory impairment of patients who chronically use corticosteroids.

Adrenal Cortex Hormones↗
PubMed2002

Development and application of a standardized assay for chemical disinfection of coccidia oocysts.

The development and application of a standardized model for testing of anticoccidial disinfectants are described. Due to its economic impact, tenacity of oocysts, and reproducibility of the course of infection Eimeria tenella has been chosen as test organism. Oocysts of the Houghton strain were more susceptible to disinfection with 4% TP4 (Preventol) than oocysts of a field isolate (FI 292/1) as determined by sporulation inhibition and lysis. Scoring of intestinal lesions and of oocyst numbers in mucosal scrapings in chicken infected with various doses of oocysts were found unsuitable for assessment of disinfectants. Because strain differences were observed only Houghton strain oocysts were applied for further testing. Guidelines for standardized in vivo testing of disinfectants have been stipulated by the German Veterinary Society (DVG) on the basis of these studies. When applied for testing of Neopredisan (NP) in two separate laboratories similar results were obtained. Inhibitory activity (IA; proportion of inactivated oocysts) of 92.9 and 90.6% were calculated for 3% NP and of 95.2 and 96.8% for 4% NP after treatment with the disinfectant over 120 min. According to the guidelines IA of at least 95% is required for certification of sufficient disinfecting efficacy by the DVG.

Animals↗