Research 2008

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Faculty of Health Sciences
School of Medicine
Department of Anatomy

Selected Highlights from Research Findings

The murine Balb/c asthma model has been used successfully for a number of in vivo immunological applications and for testing novel therapeutics. It is a reliable, clinically relevant facsimile of the human disease. The researchers focused on whether or not this model could be used to study other components of the human body, for instance ultrastructure. They studied the effect of the phytomedicine Euphorbia hirta (used to treat asthma) on the ultrastructure of fibrin, as well as platelets and cellular structures that play an important role in the coagulation process. Hydrocortisone is used as a positive control. Ultrastructure of the fibrin networks and platelets of control mice were compared to asthmatic mice that were treated with two concentrations of hydrocortisone and one concentration of the plant material. Results indicated that control mice possessed major, thick fibres and minor thin fibres, as well as tight round platelet aggregates with typical pseudopodia formation. The minor fibres of the asthmatic mice had a netlike appearance covering the major fibres, while the platelets seemed to form loosely connected, granular aggregates. Both concentrations of hydrocortisone made the fibrin more fragile and the platelet morphology changed from a tight platelet aggregate to a more granular aggregate not closely fused to each other. The researchers concluded that E. hirta does not impact on the fragility of the fibrin and that it prevents the minor fibres from forming the dense netlike layer over the major fibres, as is seen in untreated asthmatic mice. This ultrastructural morphology might give researchers better insight into asthma and possible new treatment regimes
Contact person: Prof E Pretorius.

The use of the artificial sweetener, aspartame, has long been contemplated and studied by various researchers, as well as people concerned about its negative effects. Aspartame is composed of phenylanaline (50%), aspartic acid (40%) and methanol (10%). Phenylanaline plays an important role in neurotransmitter regulation, while aspartic acid is also thought to play a role as an excitatory neurotransmitter in the central nervous system. Glutamate, asparagines and glutamine are formed from their precursor aspartic acid. Methanol, which forms 10% of the broken-down product, is converted in the body to formate, which can either be excreted or can give rise to formaldehyde, diketopiperazine (a carcinogen) and a number of other highly toxic derivatives Previously, it has been reported that the consumption of aspartame could cause neurological and behavioural disturbances in sensitive individuals. Headaches, insomnia and seizures are some of the neurological effects that have been encountered, and this may be accredited to changes in regional brain concentrations of catacholamines, which include norepinephrine, epinephrin and dopamine. The aim of this study was to identify the direct and indirect cellular effects of aspartame on the brain. The researchers found that excessive aspartame ingestion might be involved in the pathogenesis of certain mental disorders, as well as in compromised learning and emotional functioning
Contact person: Prof E Pretorius.

Platelets and fibrin play an important role in the coagulation process where they are involved in the maintenance of haemostasis. Fibrin dysfunction is associated with the development of vascular complications, while proneness to the formation of tight and rigid fibrin networks is independently associated with thrombotic disease. Rabbits have long been used successfully as animal models, and are often the species of choice for models of antithrombotic efficacy. It was previously shown that rabbit and human platelet and fibrin morphology are very similar in ultrastructure and fibrin fibre thickness. It was also previously reported that the thin minor fibres form a thick, fine network cover over the major fibres during pregnancy. According to research, white blood cell counts also change during pregnancy and stay changed for up to six weeks post partum, where the number of neutrophils increased and the number of lymphocytes, basophils and eosinophils decreased. The researchers showed that the same ultrastructure and white blood cell count changes occurred in lactating rabbits (four weeks post partum). They found that a rabbit morphology model studying platelet and fibrin morphology can be used successfully, either to study the effect of pharmaceutical products to be used during lactation and pregnancy in humans, or in veterinary research. Furthermore, the effects of pharmaceutical products on immunology and white blood cell counts can possibly also be used successfully
Contact person: Prof E Pretorius.

Platelets form an integral part of the coagulation process and their ultrastructure can provide valuable information regarding diseases associated with haemostasis. During coagulation, platelets aggregate. This aggregation can be achieved in vitro by adding thrombin to platelet-rich plasma. Previous research showed that human thrombin could be used successfully to activate mouse platelets. When conservative changes are included, the amino acid similarity between human and mouse thrombin is approximately 75%. In this qualitative study, the researchers compared the ultrastructure of mouse platelet aggregates activated by human thrombin, as well as two concentrations of mouse thrombin, using the scanning electron microscope. Results show that both human and mouse thrombin activate platelets to form aggregates with typical pseudopodia formation. Magnification up to 250 000 times showed membrane morphology with the open canalicular system pores visible in both the mouse and human-activated platelets. It is, therefore, concluded that mouse platelets can be successfully aggregated using either mouse or human thrombin
Contact person: Prof E Pretorius.

Several haematological abnormalities associated with HIV have been documented. However, the mechanisms responsible for the cytopenias in AIDS patients are complex and not always completely understood. Thrombocytopenia, which occurs in about 40% of patients with HIV infection, may be caused by increased peripheral platelet destruction, a defect in platelet production due to the impaired formation of platelets by HIV-infected magakaryocytes, or a combination of these. The aim of this study was to compare the morphology of the platelet aggregates in platelet-rich plasma (PRP) clots prepared from HIV patients with those of controls without HIV. These platelet aggregates were studied using the scanning electron microscope to determine the effect of the virus on platelet ultrastructure. The results showed that although the platelets aggregate, the morphology was changed with membrane blebbing, as well as torn cellular membranes. Membrane blebbing is typically associated with apoptosis. It is concluded that the altered morphology of platelet aggregates in HIV patients may be related to thrombocytopenia as a result of peripheral platelet destruction
Contact person: Prof E Pretorius.

Examination of the histological structure of bone not only helps investigators estimate age at death, but can also aids in the diagnosis of palaeopathological lesions. The purpose of this research project was to assess whether histological features, as described in the literature, can confirm the macroscopic diagnoses of ossified subperiosteal haematomas, associated with healed scurvy, and syphilitic bone changes observed on the anterior tibiae of individuals from a 19th century mining community from Kimberley, South Africa. The frequent occurrence of these two diseases among the deceased was well established in related hospital and government documents. A section of bone was removed from lesions on the tibiae of 14 individuals. These bone changes were macroscopically diagnosed as being indicative of treponematosis, ossified subperiosteal haematomas or non-specific periostitis. Cross-sections were prepared for microscopic investigation, using a manual ground section technique. Ossified haematomas were histologically identified in seven individuals. These sections were characterised by normal cortical bone, an intact original periosteal surface and newly formed, radiating trabecular bone apposing it. Three phases of ossified subperiosteal haematoma formation and remodelling could be distinguished. Infectious bone changes, most likely associated with treponematosis, were observed in one individual. These were characterised by lysis and numerous resorption holes/channels. No clear distinction could be made between the internal spongy, cortical or newly formed bone. Histological features described by some authors as characteristic of this condition could not be identified. In addition, three individuals presented with microscopic features indicative of both the aforementioned bone affections, and three did not show any pathological changes on the microscopic level. It was concluded that, although specific pathological conditions can most likely not be diagnosed purely on the basis of histomorphological observations, broad distinctions could be made between lesions caused by the ossification of subperiosteal haematomas and bone changes due to infectious diseases
Contact person: Prof M Steyn.

Trauma is the result of violent, accidental or therapeutic events that cause physical or psychological injury. The frequencies and types of trauma in a population can give important information regarding their lifestyle, as well as the quantity and quality of medical care available to them. The purpose of this study was to assess the incidence of trauma in the Gladstone sample population with regard to the presence of interpersonal violence, a hazardous working environment, strenuous working requirements and the availability of medical care. The individuals studied were diamond miners from Kimberley, dating to the late 19th century. A total of 107 well-preserved skeletons were excavated from unmarked graves after accidental discovery. This sample included 86 males, 15 females and six individuals of unknown sex. The majority of individuals (71%) were between 19 and 45 years of age. The remains were most likely those of migrant mine workers of low socio-economic status who had passed away at local hospitals. All bones were visually assessed for macroscopic indications of traumatic bone alterations and compared to standard palaeopathological texts and photographs. A total of 27% (nž28) of the individuals in the sample presented with well-healed, healing or perimortem fractures. Fractures to the skull encompassed 49% (nž20) of all the fractures that were observed. A total of six (6%) amputations were noted. Spondylolysis was observed in 7% (nž7) of the individuals in the sample and longstanding subluxation was noted in two individuals. The high incidences of cranial fractures in this population suggest high levels of interpersonal violence, while long bone fractures, spondylolysis and evidence of longstanding subluxations are indicative of the strenuous work requirements and the high-risk environment to which these individuals were exposed. When considering the presence of well-reduced fractures and healed amputations, it seems that adequate medical care was available to at least some members of this community
Contact person: Prof M Steyn.

Throughout history, scurvy has been a well-known disease that develops due to restricted sources of fresh fruit and vegetables. The condition results from an extended limited intake of vitamin C. Although skeletal lesions associated with infantile scurvy have been well described by many authors, very little literature is available on adult scurvy and the resulting skeletal lesions. The purpose of this study was to investigate the skeletal remains of a 19th century mining population from Kimberley, South Africa, for any skeletal lesions that may be indicative of adult scurvy. Scurvy is well documented as being extremely prevalent in this population. The skeletal remains of 107 individuals, presumed to have died around 1898, were studied. The majority of these individuals were males between 19 and 45 years of age. It is likely that most individuals were migrant workers at the diamond mines. All bones were visually assessed for macroscopic indications of pathological bone alterations associated with healed scurvy. Bone samples were also taken from ambiguous lesions in order to perform histological investigations. Lesions indicative of possible healed adult scurvy were observed in 16 individuals. These lesions included bilateral ossified haematomas, osteoperiostitic bone changes and periodontal disease. Histological investigation confirmed the presence of ossified haematomas on the anterior tibiae of some individuals. Hospital records and historical documents describing the incidence of scurvy in the local hospitals and the daily diet of the black mine workers supported these findings
Contact person: Prof M Steyn.

Research on the life expectancy of the Venda population was published in 2008 and provides information on the mortality rates of rural South African groups from this region. The purpose of this study was to apply abridged life tables to estimate life expectancy from both skeletal remains and death registry information of modern South African communities. Comparisons were also made with prehistoric and contemporary groups to better evaluate life expectancy for this time period. The sample consisted of 160 skeletons of known Venda origin and burial registry information for 1 364 black South Africans from the Rebecca Street and Mamelodi cemeteries in Pretoria, South Africa. Standard anthropological techniques were applied to determine sex and estimate age from the skeletal remains. Both stationary and non-stationary life table models were used to analyse the data. A high rate of child mortality, low juvenile and adult mortality, with a steady increase in mortality after the age of 30 years was observed for both the Venda and the cemetery samples. Throughout the 20th century, life expectancy was shown to increase for black South Africans. However, due to the widespread HIV/AIDS infection of the 21st century, infant and young adult mortality rates continue to rise to the extent that the decline in mortality seen for South Africans in the last 50 years will most likely be lost in the next decade due to this disease
Contact person: Prof M Steyn.

 

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