Molecular mechanism of tualang honey on 12% cholesterol diet induced nonalcoholic steatohepatitis (NASH) animal model

This study aimed to examine the effects of tualang honey against the high cholesterol diet induced biochemical and histological changes in the kidney, liver and pancreas. Methods: Female Sprague-Dawley rats were used where the control group (n = 5) was fed with commercial rat pellet; the high cholesterol diet (HCD) group (n= 5) was given 12% cholesterol diet; while the HCD with tualang honey (HCD+TH) group (n =5) was fed with 12% cholesterol diet with daily 1.4 g/kg/day of tualang honey. Biochemical analyses for lipid profile and renal function test were performed at completed 48 hours, 7 days, and 6 weeks. The rats were sacrificed at completed 6 weeks and the kidneys were harvested and subjected to histopathological examination. Blood biochemical analysis were also analysed at 1 week and 6 weeks for liver function test, fasting insulin, fasting glucose and HOMA-IR. The liver and pancreas tissues were harvested at the end of 6 weeks for histological examination. Results: The cholesterol diet induction resulted in dyslipidaemia and abnormal liver function. The HCD+TH group have shown an increase in total cholesterol, LDL-c, ALP levels and decreased TG, HDL-c and AST levels significantly at the end of 6 weeks compared to HCD group. Consumption of 12% cholesterol diet for six weeks resulted in an increment of the mean serum creatinine level of the HCD and HCD+TH groups to 1.5 times the control level at the completed 7 days. Also overall both the mean serum creatinine and blood urea levels were higher in HCD group than the control group. With tualang honey supplementation, the mean serum creatinine level showed significant reduction at 48 hours in the HCD+TH group as compared to the HCD group. There was also a reduction in the mean serum creatinine level at the completed 6 weeks. . Histopathologically the kidneys exhibited segmental mesangial hypercellularity and mesangial matrix expansion of almost all the glomeruli in both HCD and HCD+TH groups. The mean plasma glucose level was elevated at 1 week in the HCD group. Plasma insulin levels were higher in HCD+TH group at both 1 and 6 weeks. The HOMA-IR was also higher at 1 week in the HCD+TH group. The liver histology of both HCD and HCD+TH groups showed steatohepatitis with minimal hepatocyte degeneration while the pancreatic sections revealed no abnormalities. Conclusion: The 12% cholesterol diet of 6 weeks duration in this study did induce some features of NASH with dyslipidaemia with abnormal liver profile and also acute kidney injury. The tualang honey exerts some degree of renoprotective effect against high cholesterol diet induced kidney injury, but exhibited no effect on dyslipidaemia and histopathological changes in liver and pancreas

Smoker desaturation during general anaesthesia: a case report

We report a case of sudden hypoxaemia after intubation in a patient who had smoked a few hours prior to a surgical procedure. The cause of his desaturation was not related to bronchial secretions, bronchospasm or obstruction of the upper airways but most likely due to reduced oxygen saturation in the body prior to surgery. We managed to secure the airway and prevent prolonged desaturation by instituting remedial measures. Our conclusion is that cessation of smoking is very important and need to be emphasized in all patients having surgery under general anaesthesia. This applies to emergency cases as well

The effect of low dose organic arsenic exposure on inflammatory genes expression in rat’s kidney

Monosodium methylarsonate (MSMA) is an organic arsenical pesticide widely used in agriculture. Exposure to arsenic has been linked with multiple health problems. Inflammatory genes such as interleukin 6 (IL-6) and interleukin 8 (IL-8) play an important role in the pathophysiology of exposure to an acute high dose arsenic-mediated nephrotoxicity, which led to the proximal tubular injury. However, studies focusing on low dose organic arsenic exposure and its adverse effects on kidneys are limited. This study aimed to evaluate the effects of low dose arsenic exposure on the inflammatory genes expression in rats’ kidneys at three different duration intervals; 2 months, four months and six months. Thirty-six male Sprague-Dawley rats were randomly divided into six groups (n=6); a treatment group and its control for each interval. The treatment groups were given daily oral gavage of MSMA at 63.0 mg/kg body weight (BW) which is equivalent to 1/20 LD50 of MSMA. While control groups received distilled water via oral gavage. At the end of study intervals, the kidney tissues were harvested for arsenic level analysis and molecular analysis. The RNA integrity was confirmed with Qiaxcel analysis. The expressions of inflammatory genes were analysed using RT2 SYBR Green qPCR Mastermix. Tissue arsenic concentration was higher in all treated group. Both IL-6 and IL-8 showed a similar pattern of expressions. Organic arsenic down-regulated IL-6 and IL-8 in 2-month (both fold change -1.03) and 6-month groups (fold change -1.36,-1.15). However, in the 4-month group, both IL-6 and IL-8 were up-regulated (both fold change 1.31). Interestingly, these findings suggest that low dose arsenic exposure has shown the anti-inflammatory effect at 2-month and 6-month. However, 4-month paradoxically demonstrated a pro-inflammatory effect consistent with the tissue arsenic levels

Oral Analgesia 24 hours after major operation: A Comparative Study Of Oral Calecoxib and Tramadol in Patients Undergoing Major Gynaecological Operation

Adequacy of postoperative pain control is one of the most important factors in determining when a patient can be safely discharged from a surgical facility. Furthermore, it has a major influence on the patient’s ability to resume the normal activities of daily living. Tramadol is a weak opioid analgesic that acts mainly on μ-opioid receptor and has been proven to provide effective and safe analgesic to post-operative patients. Celecoxib (celebrex) is a highly selective COX-2 inhibitor. It belongs to nonsteroidal anti-inflammatory drugs (NSAIDs) group which reduces inflammation and pain while minimizing gastrointestinal adverse reaction. This selectivity feature makes celecoxib an attractive alternative to opioids for the control of postoperative pain. The purpose of this study was to evaluate the effectiveness of oral celecoxib, in comparison with oral tramadol, in term of analgesic properties and the need for additional tablet acetaminophen as rescue pain reliever in patients undergoing elective gynecological operation. A randomized, single-blinded study was conducted on 100 ASA I and II patients who were randomized into two groups: tramadol or celecoxib. Following major gynaecological surgery, all patients were given standard patient-controlled analgesia (PCA) regime with intravenous morphine. Patients either received oral tramadol 100 mg 8 hourly or oral celecoxib 200mg 12 hourly for analgesia 24 hours post operation. Tablet acetaminophen was available as a rescue analgesic. Patients were monitored for pain according to Modified Pain Score, haemodynamic changes and side effects. They were evaluated at 24, 32, 40 and 48 hours post operation. The mean pain score at 24, 32, 40 and 48 hours post operation were 0.86 ± 0.45, 0.68 ± 0.47, 0.42 ± 0.50, and 0.14 ± 0.35 in celecoxib group and 0.92 ± 0.44, 0.78 ± 0.41, 0.46 ± 0.54 and 0.18 ± 0.39 in tramadol group respectively. There were no significant differences in the mean pain score and between the two groups at each point of assessment (p>0.05). None of the patients requested for tablet acetaminophen. Patient satisfaction was similar in both study groups. This study indicates that oral celecoxib 200 mg 12 hourly is adequate and suitable to be used as an alternative to oral tramadol 100 mg 8 hourly in controlling pain 24 hours following major operation without the need for additional tablet acetaminophen

Chronic organic arsenic induced liver ultra structural damage

Introduction: Inorganic arsenic is one of the environmental toxins that has been associated with increased risk of cardiovascular diseases and vascular contributions to liver diseases. It has generally been thought to be more toxic than organic arsenic. In human liver, inorganic arsenic promotes vascular remodelling, portal fibrosis and hypertension. The purpose of the current study was to determine whether chronic exposure to organic arsenic impair liver ultrastructure as in inorganic arsenic exposure. Materials and Methods: Twenty eight male SpragueDawley rats were divided into 2 groups with their own control group. They received oral intubation of monosodium- methylarsonate (MSMA) at 63.30 mg/kg body weight for 4 and 6 months duration respectively while the control groups received distilled water. The liver of euthanized rats were perfused- fixed with glutaraldehyde for transmission electron microscopy processing. Results: TEM revealed a marked reduction in the number of mitochondria in both treatment groups. Some typical features of apoptosis are present with pyknotic nuclei of hepatocytes and disintegrated hepatic cytoplasm in 4- month groups. The microvilli of hepatocyte are almost completely absent with the presence of many fibre bundles (collagen fibres) widening the space of Disse. In 6-month treatment group, disintegrated cytoplasms are more prominent with degrading mitochondria of varying stages. Liver sinusoidal endothelial cells (LSEC) of 6-month treatment group are noted to have chromatin condensation with few caveolae seen. Conclusion: Chronic exposure of MSMA leads to necrotic changes of hepatocytes and apoptotic changes in LSEC and collagenisation in the space of Disse

Liver Sinusoidal Endothelial Cell (LSEC) isolation following a liver perfusion technique

Introduction: Liver perfusion has been the standard method to digest and isolate liver cells including liver sinusoidal endothelial cells (LSEC). Poor cannulating skills through portal vein results in a waste of animal resource. Familiarization of both liver perfusion technique and adhering strictly to aseptic technique during cell handling ensure high cell yield, minimum morphology disruption and cell contamination. We aimed to present a method of liver perfusion procedure followed by the isolation of LSEC. Materials and method: The study was conducted with the approval of IACUC committee. Seven Sprague Dawley rats underwent these procedures under anaesthesia. Liver perfusion was done as previously described. Briefly, LSEC were isolated by liberase enzyme perfusion of the liver, isopycnic sedimentation in a two- step Percoll gradient and selective adherence. The purification and cultivation of LSEC was evaluated by light and electron microscopy. Results: Purity and viability of LSEC after selective adherence was 80.5 ± 3.5% and ≥ 95 %, respectively. The average concentration of the cells ranged from 32 - 75 x 106 per 400 gm rat. After 8 hours of culture, LSEC monolayers were contaminated with less than 5% of other cells. Conclusion: This method is reliable and reproducible for the isolation of LSEC to enable the study of structure and function of these cells in vitro. However, improvement on the perfusion skills and isolation technique are vital to ensure better cell purity

Paraoxonase-1 activities and procalcitonin levels in sepsis and non-infectious systemic inflammatory response syndrome patients in a tertiary intensive care unit

Sepsis and septic shock remain to be a leading cause of death in the intensive care unit (ICU), including in Malaysia. Distinguishing early sepsis from non-infectious systemic inflammatory response syndrome (SIRS) may be difficult upon presentation. Thus, research has been ongoing in finding a specific and effective marker for sepsis, where paraoxonase-1 (PON1) has shown to be a promising contender. PON1 is a high density lipoprotein associated enzyme, where early researches have shown that its activities decrease as oxidative stress increases in intensity during sepsis. This study aimed to compare PON1 activities between sepsis and non-infectious SIRS patients, as well as comparing its activities in patients who ultimately survived or died as a result of their ordeal. In addition, this study looked into the diagnostic and predictive performance of PON1 for sepsis and mortality as well as the correlation between PON1 activities and a known sepsis marker, procalcitonin (PCT). This prospective observational study, recruited ICU patients above the age of 18 with SIRS and divided them into sepsis and non-infectious SIRS based on clinical assessment with or without positive cultures. PON1 activities; paraoxonase (PON) and arylesterase (ARE) activities, and PCT levels were measured daily over the first three days of ICU admission. Out of the 239 patients recruited, 164 (69%) had sepsis and 68 (28.5%) died in hospital. Results showed significantly lower PON1 activities in sepsis compared to non-infectious SIRS throughout the three-day. PON1 activities were also significantly lower in non-survivors compared to the survivors Further analysis also showed that ARE activity to be a slightly better detector of sepsis than PON activity (PON AUC 0.64-0.65 versus ARE AUC 0.67-0.69), but similar in power in predicting mortality (ARE AUC 0.61-0.64, PON AUC 0.62-0.64). PON1 activities and PCT levels were all significantly correlated with weak to moderate correlation with r-values between 0.207- 0.476. We concluded that PON1 activity measured early on ICU admission has a big potential to be a biomarker in distinguishing sepsis from non-infectious SIRS and in prediction of mortality. A larger scale study, involving multiple centres could be done to further confirm or refute these findings

A Study of Paraoxonase (PON-1) Activity and Concentration in Coronary Artery Disease Patients in Kuantan, Pahang

Introduction: Paraoxonase 1 (PON1) is a high density lipoprotein (HDL) associated enzyme that is known to inhibit oxidative modification of low density lipoprotein (LDL), thus implicated in the pathogenesis of atherosclerosis and coronary artery disease (CAD). It has been suggested that the variability in this enzyme activity is attributed to polymorphism in PON-1 gene. Nevertheless, even within the same genotype, PON-1 activity and concentration has been shown to vary widely between the different individuals. Therefore, recent studies in various populations have emphasized on the importance of measuring the PON1 activity and concentration in assessing the risk of CAD. The data of such study is however scarce in Malaysia. Objective: The aim of this study was to compare the PON-1 activities and concentration between the healthy controls and CAD patients. Methods: A comparative cross sectional study was carried out on 187 CAD patients in Tengku Ampuan Afzan Hospital, Kuantan and 188 healthy controls. Serum samples were analyzed for PON-1 activities towards paraoxon and phenylacetate as well as for HDLcholesterol. PON1 concentration was expressed as PON1 activity per mmol of HDL. Results: Serum PON-1 activities as well as concentration were found to be lower in CAD patients than in the healthy controls but the results were not significant (p > 0.05). Conclusion: Our finding suggested that PON1 activities and concentration were similar between healthy control and CAD patients in Kuantan, Pahang. A multicentre study may be required to confirm our findings in Malaysian population

Effect of Tualang honey in acute kidney injury animal model

BACKGROUND: Many researches have proven that there exists a complex association between progressive renal damage and hypercholesterolemia. However, there was little information about the early effect of hypercholesterolemia on the kidney. Additionally, although there is a growing insight into the causes and mechanisms of these diseases, preventive and therapeutic measures are still few. Hence, the aim of this study is to determine the acute and sub-acute effects of high cholesterol diet on the kidney, and to examine the protective role of tualang honey against these disease. METHODOLOGY: Fifteen female Sprague-Dawley rats were randomly divided into three groups: control group, fed with commercial rat pellet; high cholesterol diet group (HCD), fed with 12% cholesterol diet with 0.3% cholic acid, and HCD with tualang honey supplements at 1.4 g/kg/day orally group (HCD+TH). Biochemical analyses for lipid profile and renal function test were performed at completed 48 hours (day 3), day 7, and day 42 of the experiment. The rats were sacrificed at completed day 42 and the kidneys were harvested and subjected to histopathological examination. The data were analysed using ANOVA and LSD Post-Hoc test. RESULTS: Consumption of 12% cholesterol diet for six weeks resulted in an increment of the mean serum creatinine level of HCD and HCD+TH groups to 1.5 times the control level at the completed day 7. Also overall both the mean serum creatinine and blood urea levels were higher in HCD group than the control group. The mean TC showed an increasing trend throughout the experiment with the level being significantly higher than the control group at the completed day 42. A significantly higher mean serum LDL-c in the HCD group as compared to the control at the completed day 42 was also documented. The mean serum TG levels were higher than that of the control group at the completed 48 hours and day 7. The mean serum HDL-c showed a significant reduction in HCD group than the control group at the completed day 42. With tualang honey supplementation, the mean serum creatinine level showed significant reduction at 48 hours in the HCD+TH group as compared to the HCD group. There was also a reduction in the mean serum creatinine level at the completed day 42. As for the lipid profile, honey supplementation significantly reduced the mean TG and vLDL-c at the completed day 7 as compared to HCD group. Histopathologically the kidneys exhibited segmental mesangial hypercellularity and mesangial matrix expansion of almost all the glomeruli in both HCD and HCD+TH groups. CONCLUSION: The 12% cholesterol diet utilized in this study caused acute and sub-acute kidney injuries in the animal model while tualang honey at 1.4 g/kg/day orally exhibited lipid lowering activities and some degree of renoprotective effect against high cholesterol diet induced kidney injury

Retention of Knowledge in Preclinical Disciplines by Clinical Students in the IIUM Medical Programme

Introduction: A thorough knowledge in the various disciplines of the basic sciences is a major importance for the practice of clinical medicine. Many basic sciences teachers share a common concern that much of what they teach in preclinical phase is soon forgotten when students move to clinical years. Objective: To examine the retention of such knowledge by clinical students in the Medical Programme of International Islamic University Malaysia (IIUM). Methods: Sixty seven Year 3 and 64 Year 5 students undergoing the Paediatric posting rotation of the academic sessions 2011/2012 were included into this study. Open-ended, short-answer questions of the completion type in the disciplines of anatomy, physiology, biochemistry and general pathology constructed by experts were used. These questions were used to test the retention of the above stated knowledge. Self-administered questionnaire was also designed to obtain the perceptions of students on the learning of basic medical sciences. Results: A significant difference was seen between the mean total scores for the Year 3 and Year 5 students in the basic medical sciences knowledge tests (31.9% vs. 37.7%; p = 0.002). Year 5 students showed significantly higher retention of knowledge on anatomy and biochemistry (p<0.001 and p=0.021). Overall in approximately 50% of the questions students indicated that they knew the answers but could not recall. Seventy percent of students stated that they only attempted to retain facts that they perceived as important. Almost all the students (96.2%) agreed that they remembered information better due to vertical integration in the curriculum. Conclusions: This study did not see deterioration in the retention of knowledge in basic medical sciences as the clinical students progress through clinical years. Students stated that the integration of knowledge in basic medical sciences disciplines into the clinical sciences during the preclinical years helped them remember facts better