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Biomedical subjects

E Pretorius

Publications and source records attributed to E Pretorius.

At least 19 recordsLinked to original sources

Investigation into the usability of geometric morphometric analysis in assessment of sexual dimorphism.

Understanding sexual dimorphism is very important in studies of human evolution and skeletal biology. Sexual dimorphic characteristics can be studied morphologically and metrically, although morphologic studies pose several problems such as difficulties with quantification and interobserver error. Geometric morphometrics is a relatively new method that allows better assessment of morphologic characteristics. This paper aims to investigate the usability of this method by assessing three different morphologic characteristics in a sample of South African blacks: shape of the greater sciatic notch, mandibular ramus flexure, and shape of the orbits. Relative warps, thin-plate splines, and canonical variates analysis (CVA) analyses were performed. As expected, the shape of the greater sciatic notch provided the best separation between the sexes. Surprisingly, however, the shape of the orbits performed better that ramus flexure. Several possible explanations for this result are possible, which include the possibility that orbit shape is more sexually dimorphic than previously expected, or that biological reality is not reflected by this technique. More research is, however, needed.

Black People↗

Cavernous sinus anatomy as a basis for interpretation of the clinical picture and radiological investigations in a case of Entomophthorales infection.

Several cranial nerves traverse the cavernous sinus producing the typical symptom complex seen during cavernous venous sinus thrombosis in Mucorales infection. Fungi of the order Entomophthorales display different pathological and histological characteristics although belonging to the same class of fungi. A case is presented, wherein the anatomy of the cavernous sinus forms the basis in explaining the presenting symptoms of a patient with Entomophthorales infection. The anatomical explanation for the presenting neurological symptoms is confirmed by radiological investigations and further supports the diagnosis of Entomophthorales infection.

Adult↗

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↗

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↗

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↗

Rhino-orbitocerebral entomophthoramycosis.

Conidiobolus coronatus is recognized as a human pathogen causing subcutaneous fungal infection of the face in immunocompetent patients. The disease process is usually benign. We report, what we believe to be the first case of intracranial extension of C. coronatus producing rhino-orbitocerebral syndrome, and subsequent dissemination of C. coronatus in an immunocompetent patient.

Adult↗

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↗

Geometric morphometric analysis of mandibular ramus flexure.

Many characteristics of the human skeleton can only be assessed morphologically, which may be problematic due to factors such as interobserver error and difficulties with standardization. Flexure of the mandibular ramus is one of these traits, and various researchers found widely differing results using this morphological feature. The aim of this study was to determine whether differences between male and female mandibular rami could be observed using the computerized method of geometric morphometrics, a valuable tool that helps quantify shape differences. Twenty-eight mandibular rami of black females and 43 of black males were photographed in a standard plane and assessed. It was found that the females were more scattered on the graph (more variable in shape), while the males clustered more around the center point where the two axes met (shape more constant). There was, however, considerable overlap between the sexes. Although different tendencies exist between the rami of males (being more flexed) and females (tending to be straight), the extent of these differences is not adequate to predict the sex of a single individual.

Adult↗

Mandibular landmarks as an aid in minimizing injury to the marginal mandibular branch: A metric and geometric anatomical study.

Iatrogenic injury to the marginal mandibular branch is an important reason for medicolegal actions. The aim of this study was to determine the distance of the marginal mandibular branch to the inferior border of the mandible as well as variation of nerve position in relation to this border. The marginal mandibular branch was dissected carefully in a number of 36 facial halves. Three points were identified on the inferior border of the mandibular ramus: Point A at the angle of the mandible, Point B just anterior to the facial artery, and Point C, 2 cm anterior to Point B. A metric and geometric morphometric analysis, including thin-plate spline and relative warp analysis was done to determine the variation of nerve position in relation to these three bony landmarks. The metric study indicated a median distance from Point A to the nerve 2.3 mm inferior to Point A, 2.4 mm superior to Point B, and 10.7 mm superior to Point C. The shape analysis indicated that variation in the position of the nerve occurs most commonly at Points A and B. We conclude that these mandibular landmarks may assist surgeons in minimizing marginal mandibular branch injury and patient discomfort.

Aged↗

Calcium-mediated aponecrosis plays a central role in the pathogenesis of estrogenic chemical-induced neurotoxicity.

Estrogen is traditionally associated with females but is also present in males, and influences aspects of brain chemistry and brain morphology in males, females and also during prenatal development. Humans as well as animals are additionally exposed to environmental products that mimic estrogen activity, also known as endocrine disrupters (EDCs). This hypothesis article investigates the role of estrogen (and also EDCs) in the brain and how it influences the Ca2+ pathway. Ca2+ and its movement in and out of the cell is an extremely important ion controlling normal cell physiology. Any dysfunction in the movement from outside to inside the cell or between organelles may have fundamentally negative effects and the disturbance may even lead to apoptosis and/or necrosis. Therefore we consider whether estrogen and EDCs may alter the Ca2+ physiology and whether these changes may be one of the main causes of interference in physiology that is seen when humans and animals are exposed to EDCs. We come to the conclusion that on a molecular level Ca2+ and Ca2+ fluxes ([Ca2+]i, endocrine disrupting chemicals, redox modulation, mitochondria and cytochrome c followed by apoptosis, necrosis or most likely aponecrosis may contribute to chemical-mediated developmental toxicity. Similarly, we hypothesize that calcium-mediated aponecrosis do not only play a central role in the pathophysiology of estrogenic chemical-induced neurotoxicity, but can contribute to chemical-mediated developmental toxicity in general, thereby affecting almost all cells and organs of the living organism.

Animals↗

Asthma medication may influence the psychological functioning of children.

Asthma is a global health problem with up to 15% of children suffering from the disease. It has been shown by various researchers that symptomatic asthmatic patients have increased levels of free serotonin in plasma when compared with asymptomatic patients. Thus, some researchers suggest that reducing the concentration of free serotonin in plasma might be useful in treating patients with asthma. Low levels of serotonin, has however, been linked to various psychological conditions like depression, oppositional defiant disorder, ADHD and even conduct disorder. Research has indicated that products like methylphenidate (also known by the brand names as e.g., Ritalin, Concerta, Metadate and others) and other stimulants used for these conditions, particularly ADHD, exert their paradoxical calming effects by boosting serotonin levels in the brain. Therefore, the hypothesis suggest that some children using asthma medication that lowers serotonin levels, might present with symptoms of depression ADHD, oppositional defiant disorder and even conduct disorder. They may be using asthma medication that lowers serotonin and additionally use methylphenidate that boosts serotonin levels for e.g., ADHD. The hypothesis therefore suggests that asthmatic children presenting with psychological complaints, be treated holistically and serotonin levels measured before coming to conclusions regarding their psychological functioning.

Anti-Asthmatic Agents↗

Geometric morphometric analysis of the greater sciatic notch in South Africans.

The width of the greater sciatic notch of the pelvis is a characteristic commonly used to determine sex in unknown individuals. Recent research on South African skeletal material indicated that this feature may not be so reliable, especially in South African white males. In this study the greater sciatic notches of 115 known skeletons of South African origin were analysed using geometric morphometrics. Geometric morphometrics is a relatively new method that helps to quantify shape. Using this method, it was observed that South African black males have the typical narrow shape, while both the black and white females have typical wide notches. The white males, however, showed a very wide variation and their shapes scattered across the range. The shape of the greater sciatic notch is therefore not reliable to use in sex determination in this population group. Geometric morphometric analysis proved to be a valuable and reliable method to verify morphological characteristics observed with more traditional methods.

Adult↗

Corticosteroids, depression and the role of serotonin.

Patients frequently use medications simultaneously for different complaints, without being aware of the interactions these products may have. An example of this is the simultaneous use of corticosteroids and medications for depression, defiant or aggressive behaviour. Research has also indicated that corticosteroids lower serotonin levels. However, lowered serotonin levels may result in depression, aggression and other psychological conditions. These secondary complaints, caused by the corticosteroids and other products that lower serotonin levels, may then be treated with selective serotonin reuptake inhibitors (SSRIs) or psycho-stimulants (that are known to indirectly increase serotonin levels). The current research takes a look at lowered serotonin levels when using corticosteroids, as well as the interactions with SSRIs and psycho-stimulants. Furthermore, evidence is presented to prove the hypothesis that some individuals with asthma (e.g. children using systemic corticosteroids that lower serotonin levels) might present with symptoms of depression, attention deficit hyperactivity disorder (ADHD), oppositional defiant disorder and even conduct disorder; and that treating these secondary complaints with SSRIs and psycho-stimulants will result in the upregulating of serotonin levels, and that, in turn, will trigger asthma.

Adrenal Cortex Hormones↗

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↗

An in vitro study of biological safety of condoms and their additives.

The use of condoms to prevent sexually transmitted diseases, especially HIV, is widely encouraged. Condoms contain latex, nonspermicidal lubricants (such as dimethylsiliconium) and other nonspecified compounds, such as colorants and flavorings. Latex causes allergy reaction in susceptible individuals but little is known regarding the cytotoxic effects of other additives. The objective of this study was to develop a sensitive in vitro system to determine the toxic effects of condom material. The modified L929 FDA method and a more specific cell type, such as the cervical epithelial tumor cell line HeLa, was used. Lubricated (LC), lubricated and flavored (LFC), and lubricated, flavored and colored condoms (LFCC) were evaluated. Washings containing condom surface material were prepared by washing condom fragments in medium for different time intervals. Changes in cell number, viability and lysosome integrity in the L929 and HeLa cell lines was determined using the Crystal Violet, MTT and Neutral Red assays, respectively. The condom type affected cell viability and lysosome integrity, with LC inducing an increase in cell viability and LFC a decrease in lysosome integrity. The HeLa cell line in combination with the MTT and NR assay was themost sensitive in vitro system to determine the toxic effects of condom material.

Animals↗

Presenting an in vitro cell culture model to determine the cytotoxic effect of benzoyl peroxide vapours.

Benzoyl peroxide (BP) is an initiator of polymerisation used in the synthesis of methyl methacrylate dental materials, and is a known allergen that causes allergic contact dermatitis during occupational exposure, especially in dentists and dental personnel. The eyes of dental technicians, dentists and even patients with an allergic history are the first level of exposure, and therefore complaints of allergic reactions of the eyes are usually noted. In this article the authors used a modification direct cell culture testing method to assess the cytotoxic potential of BP. L929 mouse fibroblasts as well as cells from human limbal eye rings were exposed to BP vapours in the experiments. The MTT and crystal violet assays were also employed to determine cell numbers and viability. Results indicated that there is an exponential decrease in cell viability. After exposure of five minutes, cell viability had already decreased by 20 and 40% for vapours derived from either a 10 or 20 microliters aliquot of BP, respectively. After a further five minutes, cell viability decreased by a further 10% with a statistical difference form the control of p < 0.01. Results indicated that BP vapours are cytotoxic to mouse L929 and human eye fibroblasts. Furthermore, the authors concluded that the permanent L929 mouse fibroblast cell line can provide valuable information regarding the cytotoxic effects of dental products and associated compounds that form toxic vapours.

Animals↗