Report of XXV congress of the international academy of pathology Brisbane convention and exhibition centre, Queensland, Australia

Introduction The International Academy of Pathology (lAP) annual meeting plays an important role in updating the standard pathological diagnoses, encouraging the study of obscure disease etiologies and promoting active debate on controversial disease entities. In addition, it provides a platform for dynamic exchange of academic information and mutual collaboration between countries necessary for the prevention of diseases, especially communicable disease outbreak (such as the recent SARS and Bird flu epidemics), and in the subjugation of malignant diseases. Member countries take turn to host the meeting. Last year's meeting was in Thailand, this year is Australia and next year it will be in Beijing. Malaysian pathologists enthusiastically take part in these meetings, either as delegates, presenting research findings or as invited lecturers.(see. enclosed Program book). Conclusion On the whole, it was a very fruitful congress, and the participation was very rewarding. The amount of knowledge gained was tremendous. Further, it is always inspiring to listen to and be in presence of authorities in a particular field. This inspiration is necessary for one to continue to aim for excellence. The paper presentation was a success, although no awards was won, since it led to formation of new links and open new door of opportunity for further studies and collaboration to be performed

The expressions of Ret/PTC and p53 in normal, benign and malignant thyroid lesions

Goiter is a highly prevalent problem in the local population. Studies at HUSM have found high percentage of papillary carcinoma within this lesion. Ret/PTC is a recently discovered oncogene which is solely related to papillary carcinoma. It has been proven to play a major role in the pathogenesis of this malignant lesion. P53 gene is a well known tumour suppressor gene, usually associated with the undifferentiated thyroid carcinoma. Immunohistochemistry is able to demonstrate p53 mutation in well differentiated thyroid carcinoma. This study aims to investigate the expression of ret and p53 in the local normal, benign and malignant thyroid lesions in order to shed light on the pathogenesis of papillary carcinoma and explain the high prevalence of this condition among the nodular hyperplasia ( multinodular goiter) cases. From the records of HUSM pathology department, archival blocks from 50 follicular adenomas, 66 nodular hyperplasia cases and 53 papillary carcinoma cases were retrieved. They were studied by immunohistochemistry method for the presence of ret/PTC and p53 mutant protein within the follicular cells. Normal thyroid tissues from 74 of the cases were utilized as controls. Ret/PTC is expressed by 5.4% of normal thyroid tissue, 18% of follicular adenomas, 22.7% of nodular hyperplasia cases and 71.7% of papillary carcinomas. There is no statistically significant difference of ret expression between pure nodular hyperplasia and the ones with coexisting papillary carcinoma

THE EFFECTS OF LEPTIN ADMINISTRATION ON RENAL FUNCTION IN SPONTANEOUSLY HYPERTENSIVE RATS

Objective: Elevated levels of leptin may be responsible directly for progression and severity of renal disease in obesity and hypertension. It may exert its effects by promoting fibrosis through the actions of transforming growth factor-β1 (TGF-β1) and the Smad pathway. This study determines the effect of leptin administration on the development of renal fibrosis in nonobese spontaneously hypertensive rats (SHRs).Methods: Male SHRs, aged 12-14 weeks, were injected with either leptin (60 µg/kg/day) or saline (for the control group) subcutaneously daily for42 days. At the end of the experimental period, animals were euthanized and their kidneys were removed. The right kidney was harvested for the determination of messenger ribonucleic acid (mRNA) expression of TGF-β1, Smad2, Smad3, and bone morphogenic protein 7 (BMP7). The left kidneys were stored in neutral buffered 10% formalin until they were processed and stained with hematoxylin and eosin. Prepared slides were examined under light microscopy. 30 consecutive glomeruli were examined for the cell counts based on the number of nuclei seen and the total area of glomeruli.Results: No significant difference was evident in renal function between control and leptin-treated rats. Cellularity and area of glomeruli were also not different between the two groups. mRNA expression of TGF-β1, Smad2, and BMP7 were, however, higher in leptin-treated rats.Conclusion: It appears that 6 weeks of leptin administration increases renal TGF-β1 and Smad2 levels but with little morphological changes in the kidney. Whether the elevated BMP7 expression was responsible for lack of effect of leptin on renal morphological changes remains unclear.Keywords: Leptin, Renal function, Hypertension, Glomerulus, Transforming growth factor-β1, Smad, Spontaneously hypertensive rats

Preventive effects of tocotrienol-enriched mixed fraction on plaque formation and stability in early and established atherosclerosis

Atherosclerosis is the underlying pathology for cardiovascular disease. The preventive effects of tocotrienol-enriched mixed fraction (TEMF) on atherogenesis remain unclear. Objective: To investigate the preventive effects of TEMF supplementation on early and established atherosclerosis. Methods: Twenty New Zealand white rabbits were divided into TEMF (n=10) and placebo (n=10) groups. Treatments were given by oral gavage for 8 weeks followed by a 1% high cholesterol diet (HCD) for another two (to induce early atherosclerosis) or eight weeks (established atherosclerosis). At the end of the study, the aorta was dissected, stained with Sudan IV, and qualitatively analyzed for the atherosclerotic lesion. Immunohistochemistry was performed to detect expression of interleukin-6 (IL-6), CRP, nuclear factor kappa beta, E-selectin, intercellular adhesion molecule-1 (ICAM- 1), vascular cell adhesion protein-1 (VCAM-1), smooth muscle actin (SMA), and matrix metalloproteinase-12 (MMP-12). Results: In both early and established atherosclerosis groups, there was a significant reduction of atherosclerotic lesions in TEMF compared to placebo. Atherogenic biomarkers; IL-6, CRP, E-selectin, SMA, and MMP-12 were reduced with TEMF supplementation in established atherosclerosis (p<0.05). Neutral effects were seen in the early atherosclerosis group. Conclusion: TEMF supplementation in the preventive setting decreased atherosclerosis formation and reduces endothelial inflammation in established atherosclerosis lesions while increasing plaque stability

Alpha-mangostin (Garcinia mangostana Linn.) and its potential application in mitigating chronic wound healing

Wound healing is a complex and dynamic cellular process to restore tissue function. Current treatments for chronic wounds especially diabetic ulcers are expensive, with adverse effects. Recently, numerous researchers have focused on the potential effect of natural products on wound healing. One of them is mangosteen (Garcinia mangostana Linn). It is a well-known tropical fruit that is native to Southeast Asia. The active ingredient of mangosteen pericarp contains xanthones that exhibit a wide range of pharmacological activities, including anti-inflammatory and anti-bacterial properties which are the core elements needed in wound healing. Firstly, this review discusses the concepts of abnormal and normal wound healing mechanisms. Then an in-depth observation of the pharmacological activities of mangosteen and its derivatives was presented to study their potentially beneficial applications in the treatment of chronic wound healing which is a contemporary medical issue

The invisible evil twin of an adrenal adenoma / Aimi Fadilah M … [et al.]

Primary aldosteronism (PA) causes a persistently elevated blood pressure (BP) due to excessive release of the hormone aldosterone from the adrenal glands. Classically, it is called Conn’s syndrome and is described as the triad of hypertension and hypokalemia with the presence of unilateral adrenal adenoma. It can be cured with surgical resection of the aldosterone-secreting adenoma leading to resolution of hypertension, hypokalemia and increased cardiovascular risk associated with hyperaldosteronism. We present a case of a man with previous ischemic heart disease (IHD) who presented with resistant hypertension. Investigations for secondary causes of hypertension revealed an elevated aldosterone level and saline suppression test confirmed the diagnosis of PA. Radiological examination revealed a left adrenal adenoma and a normal right adrenal gland. However, adrenal venous sampling showed lateralization of aldosterone secretion towards the right. He subsequently underwent a laparoscopic right adrenalectomy which improved his BP control promptly. This case highlights the importance of recognizing the need to investigate for secondary causes of hypertension. It also underscores the importance of dynamic tests, which may not be easily accessible to most clinicians but should pursue, to allow a definitive diagnosis and effective treatment

Ficus deltoidea var. kunstleri extract administration in Hypercholesterolaemic, atherosclerotic rabbits: effects on organ function, morphology, and atherosclerosis development

Ficus deltoidea (FD) is used in traditional Malay medicine to treat various ailments and has been shown to be safe in toxicity studies. However, the information on the safety and efficacy of FD in the atherosclerosis-induced animal model is limited. This study aims to investigate the safety of FD var. kunstleri (FDK) extract on high cholesterol diet (HCD)-induced atherosclerotic rabbits and its efficacy in treating atherosclerosis. New Zealand White rabbits were randomly divided into two groups: G1 (1% HCD for 4 weeks) and G2 (1% HCD for 8 weeks). Each group was randomised into FDK700 (700 mg FDK/kg/day for G1 and G2), FDK800 (800 mg FDK/kg/day for G2), simvastatin (5 mg/kg/day) and placebo. The body weight, blood pressure, serum biochemistry and histopathological examination were obtained to assess any toxicity signs. Fasting lipid profile, soluble c-reactive protein (sCRP) level and atherosclerotic plaque formation were compared between treated and placebo groups to evaluate treatment efficacy. Results: No significant differences were observed in all safety parameters between the treated and placebo groups (p<0.05). FDK treatment did not show significant differences in all parameters evaluated in both treatment arms. In conclusion, FDK extract up to 800 mg/kg is safe for use in atherosclerotic rabbits. It has neutral effects on lipid profile, inflammation and atherosclerosis formation

Development of custom lead shield and strainer for targeted irradiation for mice in the gamma cell chamber

We presented a development of a custom lead shield and mouse strainer for targeted irradiation from the gamma-cell chamber. This study was divided into two parts i.e., to (i) fabricate the shield and strainer from a lead (Pb) and (ii) optimize the irradiation to the mice-bearing tumour model with 2 and 8 Gy absorbed doses. The lead shielding was fabricated into a cuboid shape with a canal on the top and a hole on the vertical side for the beam path. Respective deliveries doses of 28 and 75 Gy from gamma-cell were used to achieve 2 and 8 Gy absorbed doses at the tumour sites

Which is the best method of sterilization for recycled bone autograft in limb salvage surgery: a radiological, biomechanical and histopathological study in rabbit

Background: Limb salvage surgery is a treatment of choice for sarcomas of the extremities. One of the options in skeletal reconstruction after tumour resection is by using a recycled bone autograft. The present accepted methods of recycling bone autografts include autoclaving, pasteurization and irradiation. At the moment there is lack of studies that compare the effectiveness of various sterilization methods used for recycling bone autografts and their effects in terms of bone incorporation. This study was performed to determine the effects of different methods of sterilization on bone autografts in rabbit by radiological, biomechanical and histopathological evaluations. Methods: Fresh rabbit cortical bone is harvested from the tibial diaphysis and sterilized extracorporeally by pasteurization (n = 6), autoclaving (n = 6), irradiation (n = 6) and normal saline as control group (n = 6). The cortical bones were immediately reimplanted after the sterilization process. The subsequent process of graft incorporation was examined over a period of 12 weeks by serial radiographs, biomechanical and histopathological evaluations. Statistical analysis (ANOVA) was performed on these results. Significance level (Α) and power (Β) were set to 0.05 and 0.90, respectively. Results: Radiographic analysis showed that irradiation group has higher score in bony union compared to other sterilization groups (p = 0.041). ANOVA analysis of 'failure stress', 'modulus' and 'strain to failure' demonstrated no significant differences (p = 0.389) between treated and untreated specimens under mechanical loading. In macroscopic histopathological analysis, the irradiated group has the highest percentage of bony union (91.7 percent). However in microscopic analysis of union, the pasteurization group has significantly higher score (p = 0.041) in callus formation, osteocytes percentage and bone marrow cellularity at the end of the study indicating good union potential. Conclusions: This experimental study shown that both irradiation and pasteurization techniques have more favourable outcome in terms of bony union based on radiographic and histopathological evaluations. Autoclaving has the worst outcome. These results indicate that extracorporeal irradiation or pasteurization of bone autografts, are viable option for recycling bone autografts. However, pasteurization has the best overall outcomes because of its osteocytes preservation and bone marrow cellularity

Cellular events and biomarkers of wound healing

Researchers have identified several of the cellular events associated with wound healing. Platelets, neutrophils, macrophages, and fibroblasts primarily contribute to the process. They release cytokines including interleukins (ILs) and TNF-α, and growth factors, of which platelet-derived growth factor (PDGF) is perhaps the most important. The cytokines and growth factors manipulate the inflammatory phase of healing. Cytokines are chemotactic for white cells and fibroblasts, while the growth factors initiate fibroblast and keratinocyte proliferation. Inflammation is followed by the proliferation of fibroblasts, which lay down the extracellular matrix. Simultaneously, various white cells and other connective tissue cells release both the matrix metalloproteinases (MMPs) and the tissue inhibitors of these metalloproteinases (TIMPs). MMPs remove damaged structural proteins such as collagen, while the fibroblasts lay down fresh extracellular matrix proteins. Fluid collected from acute, healing wounds contains growth factors, and stimulates fibroblast proliferation, but fluid collected from chronic, nonhealing wounds does not. Fibroblasts from chronic wounds do not respond to chronic wound fluid, probably because the fibroblasts of these wounds have lost the receptors that respond to cytokines and growth factors. Nonhealing wounds contain high levels of IL1, IL6, and MMPs, and an abnormally high MMP/TIMP ratio. Clinical examination of wounds inconsistently predicts which wounds will heal when procedures like secondary closure are planned. Surgeons therefore hope that these chemicals can be used as biomarkers of wounds which have impaired ability to heal. There is also evidence that the application of growth factors like PDGF will help the healing of chronic, nonhealing wounds