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Biomedical subjects

D F Du Toit

Publications and source records attributed to D F Du Toit.

At least 19 recordsLinked to original sources

Islet cell response in the neonatal rat after exposure to a high-fat diet during pregnancy.

Although pancreatic beta-cells are capable of adapting their mass in response to insulin requirements, evidence has shown that a dietary insult could compromise this ability. Fetal malnutrition has been linked to low birth weight and the development of type 2 diabetes later in life, while reduced beta-cell mass has been reported in adult rats fed a high-fat diet (HFD). Reported here are the effects of exposure to a HFD, during different periods of gestation, on neonatal rat weight and beta- and alpha-cell development. The experimental groups were composed of neonatal offspring obtained from Wistar rats fed a high-fat (40% as energy) diet for either the first (HF1), second (HF2), or third (HF3) week, or all three (HF1-3) weeks of gestation. Neonatal weights and circulating glucose and insulin concentrations were measured on postnatal day 1, after which the pancreata were excised and processed for histological immunocytochemical examination and image analysis. HF1 and HF2 neonates were hypoglycemic, whereas HF1-3 neonates were hyperglycemic. Low birth weights were observed only in HF1 neonates. No significant differences were detected in the circulating insulin concentrations in the neonates, although beta-cell volume and numbers were reduced in HF1-3 neonates. beta-cell numbers also declined in HF1 and HF3 neonates. alpha-cell volume, number and size were, however, increased in HF1-3 neonates. alpha-cell size was also increased in HF1 and HF3 neonates. In neonates, exposure to a maternal HFD throughout gestation was found to have the most adverse effect on beta-cell development and resulted in hyperglycemia.

Animals↗

Traumatic abdominal wall hernia--four cases and a review of the literature.

OBJECTIVE: To review blunt traumatic abdominal wall hernias (TAWHs) in our institution. METHOD: Retrospective review of blunt abdominal trauma cases over a 6-month period. RESULTS: Four patients with TAWH were identified. The mean age was 36 years. Three had been involved in vehicular collisions, and 1 had been assaulted with a large stone. All were diagnosed on presentation, 3 by computed tomography scan and 1 clinically. Two were repaired as emergencies, and 1 was repaired after 4 months. The 4th patient refused surgery. CONCLUSION: This uncommon injury requires a high index of suspicion and a low threshold for intervention. CT scan offers the best imaging potential.

Abdominal Injuries↗

Auriculo-temporal nerve. Clinicopathological relevance to facial-maxillary practice.

Anatomically, the auriculo-temporal nerve (ATN), a peripheral branch of the trigeminal nerve is in close relation to the parotid gland, neck of the mandible, temporal vessels, and sphenomandibular ligament. Fine branches of the ATN are at risk of division during surgical intervention of the parotid gland or condyle of the mandible. "Frey's syndrome", or abnormal gustatory sweating, may be a consequence of injury to the branches of the auriculo-temporal nerve. This uncommon syndrome can also occur with fractures of the temporo-mandibular joint (TMJ), due to the anatomic proximity of the nerve to the bone.

Cranial Nerve Injuries↗

Nervus lingualis: applied anatomical relevance to dental practice and oral surgery.

N. lingualis supplies general sensory branches to the mucosa of the anterior two-thirds of the tongue, sublingual mucosa and the mandibular lingual gingiva. From an oral surgery point of view, the course of the lingual nerve is critical due to the intimate medial relationship to the roots of the mandibular third molar. "Hitch-hiking" special sensory taste fibres from the chorda tympani (cranial nerve seven) are distributed to the mucosa of most of the anterior two-thirds of the tongue, together with the general sensory branches derived from the mandibular division of the trigeminal nerve. The circumvallate papilLae anterior to the sulcus terminalis are supplied by special sensory fibres (taste) of the glossopharyngeal nerve, latrogenic lingual nerve injury, subsequent to mandibular wisdom teeth removal, can result in irreversible gustatory deficits and somatosensory dysfunction. Patients undergoing oral surgery for impacted mandibular molars should be informed of the anatomical relationship of the lingual nerve to the roots, and the implications of denervation.

Humans↗

The non-human primate endocrine pancreas: development, regeneration potential and metaplasia.

An investigation into the development of the Vervet monkey endocrine pancreas revealed a sequence of occurrence of pancreatic peptides that differed from previous reports in mice, dog and human with PP and somatostatin occurring before glucagon and insulin. All four pancreatic peptides were identified, immunohistochemically, in only one of the pancreatic primordial buds, before fusion of the two buds to form the pancreas. This questions the hypothesis that the heterogeneous endocrine cell distribution seen in the adult pancreas is due to the contribution of only PP cells by the ventral bud and non-PP cells by the dorsal bud. Co-localization of glucagon and PP was observed extensively in the developing pancreas and the predominant expression of one over the other in an apparently organized non-random manner accounted for the glucagon- and PP-rich areas seen in the developing pancreas. A small number of cells immunoreactive to glucagon and PP were also observed in the adult. Reports of plasticity of differentiation of other pancreatic cells led us to investigate regeneration potential of the adult monkey pancreas. Partial obstruction of the Vervet monkey main pancreatic duct, by cellophane wrapping, resulted in duct cell proliferation and differentiation to form new endocrine tissue in a way that mimics normal organogenesis. Focal areas of hepatocytes were found in the regenerated pancreas of one monkey, illustrating further the latent developmental capabilities of adult pancreas cells. These findings could lead to interesting new therapies for pancreas and liver disease.

Animals↗

Do the pancreatic primordial buds in embryogenesis have the potential to produce all pancreatic endocrine cells?

A heterogeneity in the cellular composition of the endocrine pancreas, with a preponderance of pancreatic polypeptide cells in the lower head region, has been linked to the dual origin of the organ. The pancreas develops from a ventral bud thought to contain potential pancreatic polypeptide cells and a dorsal bud contributing the non pancreatic polypeptide cells. This does not explain, however, several anomalies including the results reported here of a homogenous distribution of non insulin cells in the foetal baboon whilst the adult pancreas exhibits a heterogenous distribution with the pancreatic polypeptide-rich area in the lower head of the pancreas. If this heterogeneity is associated with the dual origin of the pancreas, it would be expected to be more pronounced in the foetus. The anomalies could be explained if both primordial buds contained progenitor cells of all endocrine cell types which could be expressed to meet the requirements of the body at any particular time.

Animals↗

Endocrine function after hetero- and ortho-topic segmental pancreatic transplantation in primates.

This study assessed the early postoperative pancreatic endocrine function after intraperitoneal segmental hetero- and ortho-topic pancreatic allotransplantation in hemipancreatectomized, nonimmunesuppressed chacma baboons. Hemipancreatectomized animals remained normoglycaemic but rendered significantly reduced K values and insulin release during IVGTT, findings consistent with major pancreatic resection. Segmental hetero- or ortho-topic pancreatic transplantation did not improve reduced K values and hypoinsulinaemia following hemipancreatectomy although orthotopically sited grafts rendered the best glucose tolerance test curves. Glucagon output during IVGTT remained the same in both transplant models. It is concluded that the postoperative hormonal response was similar in both orthotopic and heterotopic transplant recipients, which indicates that drainage of graft venous effluent into the portal circulation has no advantage over systemic insulin drainage as reflected in this "diabetic" model.

Animals↗

Effect of cyclosporine and irradiation on experimental pancreatic allografts in the primate.

The present study assessed the effectiveness of cyclosporine (CSA) and subtotal marrow irradiation (TL1) alone, and CSA in combination with TL1 in a primate segmental pancreatic allotransplantation model. Continuous administration of CSA 25 mg/kg/day and 50 mg/kg/day resulted in mean graft survival of 21.5 days and 24.5 days, respectively. Administration of fractionated TL1 800 rad (8 Gy) and 1,000 rad (10 Gy) alone resulted in mean graft survival of 13.3 days and 14.5 days, respectively. Of 20 animals that received TL1 1,000 rad (10 Gy) and CSA 25 mg/kg/day orally for 5 days then 10 mg/kg/day intramuscularly indefinitely, 3 had graft survival of greater than 100 days. Likewise, of a group of 15 animals that received TL1 800 rad (8 Gy) and combined indefinite administration of CSA, 6 had graft survival of greater than 100 days. Although CSA and TL1 administration alone produced modest pancreatic allograft survival, a combination of IL1 (800 or 1,000 rad) and CSA resulted in highly significant segmental pancreatic allograft survival in the primate.

Animals↗

Islet cell function in long-term surviving primates after segmental pancreatic allotransplantation.

Islet cell function was studied in pancreatectomized primates with functioning segmental pancreatic allografts more than 100 days after transplantation. Segmental allograft recipients were immunosuppressed with total lymphoid irradiation (TL1) and cyclosporine (CSA). After 100 days, islet function was assessed, at which stage immunosuppression was terminated. Glucose, insulin, glucagon, and C-peptide response was assessed during intravenous glucose tolerance test (IVGTT) and during arginine and tolbutamide stimulation. In eight normoglycaemic primates in which immunosuppressive treatment had been stopped and with mean graft survival of 145 days, islet stimulation was associated with moderate glucose intolerance, reduced K-values, hypoinsulinaemia, and low C-peptide values. Postmortem findings in all animals intentionally killed revealed severe graft atrophy in the absence of significant rejection. Severe graft atrophy in normoglycaemic primates, together with significantly impaired graft function after segmental pancreatic transplantation compared to normal animals, suggest that transplantation of the whole pancreas may be mandatory if normal or near-normal function is to be achieved.

Animals↗

Significant prolongation of segmental pancreatic allograft survival in two species.

A study was conducted to assess the suppression of segmental pancreatic allograft rejection by cyclosporine (CSA) alone in baboons and dogs, and subtotal marrow irradiation (TL1) alone and TL 1 in combination with CSA in baboons. Total pancreatectomy in the dog and primate provided a reliable diabetic model, induced an absolute deficiency of insulin and was uniformly lethal if not treated. Continuous administration of CSA in baboons resulted in modest allograft survival. As in baboons, dogs receiving CSA 25 mg/kg/d rendered moderate graft prolongation but a dose of 40 mg/kg/d resulted in significant graft survival (greater than 100 days) in 5 of 8 allograft recipients. Irradiation alone resulted in minimal baboon pancreatic allograft survival of 20 baboons receiving TL1 1,000 rad and CSA, 3 had graft survival greater than of 100 days. Of 15 baboons receiving TL1 800 rad and CSA, 6 had graft survival of greater than 100 days. In conclusion, CSA administration in dogs and TL1 in combination with CSA in baboons resulted in highly significant segmental pancreatic allograft survival.

Animals↗

Distribution of cell types of the islets of Langerhans throughout the pancreas of the Chacma baboon.

Biopsies of the pancreas head, tail, and uncinate regions of four baboons were processed for immunocytochemical (ICC) studies by using avidin-biotin-peroxidase label for light microscopy (LM). Toluidine-blue- or methylene-blue-stained 0.5-micron sections of nonosmicated resin-embedded tissue were viewed to locate areas of suitable islets. For ICC investigations, batches 10 microns apart of ten consecutive 1-micron sections throughout ten islets from each of the three regions were immunolabelled for LM. Four slides in each batch were immunolabelled consecutively for insulin, glucagon, somatostatin, and pancreatic polypeptide, the fifth acting as one of the range of controls in each batch. The number of each of the four cell types was counted in at least ten immunolabelled islets from each of the pancreas heads, uncinate portions, and tails. The uncinate region and not the head, as in most mammals, was found to contain significantly higher numbers of pancreatic polypeptide (PP) cells and lower numbers of A (glucagon) and D (somatostatin) cells (P less than .001). The PP cells occurred in clumps and not as described in other mammals as part of the mantle of A, D, and PP cells. PP and A cell numbers were significantly different for each region (P less than .001), being lowest in the head for PP and in the uncinate process for A cells. D cell distribution was similar to that of the A cells whilst a significantly smaller number of B (insulin) cells was found in the tail compared with other regions (P less than .001).

Animals↗

The effect of ionizing radiation on the primate pancreas: an endocrine and morphologic study.

In this study we evaluated the endocrine, biochemical, and haematological derangements as well as pancreatic and histological changes of the bonemarrow in the primate following external fractionated subtotal marrow irradiation without bonemarrow reconstitution. The irradiation was administered in preparation for pancreatic transplantation. Two groups of animals (ten in each group) received 800 rad (8 Gy) and 1,000 rad (10 Gy) respectively over 4 to 5 weeks. A maximum of 200 rads (2 Gy) were administered weekly as photons from a 6 MV linear accelerator. During irradiation the animals remained normoglycaemic in the presence of transiently elevated liver enzymes and serum amylase values, which returned to normal on completion of the irradiation. Insulin release was significantly reduced in both groups during irradiation and was associated with minimally decreased K-values in the presence of mild glucose intolerance. Pancreatic light morphologic changes included structural changes of both exocrine and endocrine elements and included necrosis of the islet cells and acinar tissue. Islet histology demonstrated striking cytocavitary network changes of alpha and beta cells, including degranulation, vacuolization, mitochondrial destruction, and an increase in lysosomes. A hypoplastic bonemarrow ranging from moderate to severe was observed in all irradiated recipients. Near total fractionated body irradiation in the primate is therefore associated with elevated liver enzymes, pancytopenia, transient hyperamylasaemia, hypoinsulinaemia, a varying degree of pancreatitis, and bonemarrow hypoplasia.

Animals↗