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Biomedical subjects

B K Tan

Publications and source records attributed to B K Tan.

At least 19 recordsLinked to original sources

Upregulation of adiponectin receptor 1 and 2 mRNA and protein in adipose tissue and adipocytes in insulin-resistant women with polycystic ovary syndrome.

AIMS/HYPOTHESIS: Polycystic ovary syndrome (PCOS) is a multifaceted metabolic disease linked with insulin resistance (IR) and obesity. Adiponectin, which is lower in IR states, exerts its glucose-lowering and anti-inflammatory effects by activating two receptors, ADIPOR1 and ADIPOR2. There are no data on the relative expression of these receptors in adipose tissue of PCOS women. METHODS: We investigated the expression of adiponectin receptors from corresponding s.c. and omental (o.m.) adipose tissue in women with PCOS compared with matched non-PCOS women. As there is a disturbance in the steroid milieu in PCOS women, we also assessed the effects of testosterone and oestradiol on adiponectin receptors using adipocytes and adipocyte explants. Real-time RT-PCR and western blotting were used to assess the relative adiponectin receptor mRNA expression and protein production, respectively. Biochemical measurements were performed in our hospital's laboratory. RESULTS: We are the first to describe adiponectin receptor expression and production, in corresponding s.c. and o.m. human adipose tissues at the mRNA and protein level. We demonstrate the upregulation of mRNA expression and protein production of adiponectin receptors in women with PCOS, in s.c. and o.m. adipose tissue. Treatment of adipose tissue explants and adipocytes with testosterone and oestradiol induced the expression of adiponectin receptor mRNA and protein. There was a significant positive association between ADIPOR1/R2 expression and homeostasis model assessment, testosterone, oestradiol and triglycerides and a negative relationship with sex hormone-binding globulin. CONCLUSIONS/INTERPRETATION: The precise reason for the upregulation of adiponectin receptors seen in PCOS women, a pro-diabetic state, is unknown, but it appears that sex steroids may play a role in their regulation in adipose tissue.

Adipocytes↗

Effects of hormone replacement therapy type and route of administration on plasma matrix metalloproteinases and their tissue inhibitors in postmenopausal women.

BACKGROUND: Matrix metalloproteinases (MMPs) are implicated in numerous disease states including cardiovascular disease and cancer. Because recent studies have shown a detrimental effect of hormone replacement therapy on cardiovascular disease and breast cancer, we investigated whether there are any differences in the concentrations of MMPs and their tissue inhibitors (TIMPs) in women receiving various forms of postmenopausal therapy. MATERIAL AND METHODS: A total of 195 healthy postmenopausal women were assessed: 46 were taking tibolone, 47 were taking transdermal estradiol, 46 were taking conjugated equine estrogens (CEE), and 56 were not taking any menopausal therapy (CTR). Plasma levels of MMP-2 and -9 and TIMP-1 and TIMP-2 were measured by ELISA methods. RESULTS: MMP-9 levels were significantly higher in the CEE group in comparison with healthy women not receiving menopausal therapy (P < 0.05). In contrast, MMP-9 levels in the tibolone group were significantly lower than in any other group (P < 0.01, compared with transdermal estradiol and CTR, and P < 0.001, compared with CEE). MMP-9 to TIMP-1 ratio was also significantly higher in the CEE, compared with CTR (P < 0.05), and lower in the tibolone group (P < 0.01, compared with all groups). MMP-2 levels were higher in the CEE group, compared with healthy women not receiving any menopausal therapy, and women taking tibolone (P < 0.05). CONCLUSIONS: Our study demonstrates differential effects of various forms of postmenopausal therapy on serum levels of MMP-9 and MMP-2. It remains to be established whether these differences might be associated with differences in risks of cardiovascular disease and cancer in these women.

Administration, Cutaneous↗

Increased circulating levels of matrix metalloproteinase-2 and -9 in women with the polycystic ovary syndrome.

INTRODUCTION: Matrix metalloproteinases (MMPs) have been implicated in various pathological processes including inflammatory response, cardiovascular disease, and recently also in ovarian dysfunction. Polycystic ovary syndrome (PCOS) is the most common endocrinopathy in women of reproductive age and is characterized by chronic anovulation, insulin resistance, and increased prevalence of cardiovascular risk factors. Circulating levels of MMPs and their tissue inhibitors (TIMPs) so far have not been assessed in the PCOS. MATERIALS AND METHODS: Serum levels of MMP-2, MMP-9, TIMP-1, and TIMP-2 were measured in 23 women with PCOS [age (mean +/- sd), 30.5 +/- 6.7 yr; body mass index, 35.8 +/- 7.5 kg/m2] and 22 healthy, regularly menstruating women (age, 29.4 +/- 5.6; body mass index, 31.7 +/- 9.2 kg/m2). RESULTS: Women with PCOS had significantly higher concentrations of MMP-2 (999.8 +/- 155 vs. 521.8 +/- 242 ng/ml; P < 0.001), MMP-9 (592.4 +/- 279 vs. 345 +/- 309; P = 0.007), and TIMP-1 levels (823.8 +/- 145 vs. 692 +/- 210 ng/ml; P = 0.02) than control healthy women. There was no difference in TIMP-2 levels (47.3 +/- 30 vs. 44.4 +/- 39.7 ng/ml; P = 0.21) between women with PCOS and controls. CONCLUSIONS: Obese women with PCOS have elevated serum concentrations of MMP-2 and -9. It might be hypothesized that elevated MMP concentrations may be related to increased cardiovascular risk in PCOS and/or menstrual irregularities associated with this syndrome.

Adult↗

Emerging technologies for the identification of therapeutic targets for the management of pre-eclampsia.

Pre-eclampsia is a common and serious complication of pregnancy characterised by hypertension and proteinuria. Genetic and environmental factors influence the occurrence and progression of the disease. Emerging experimental systems and increasingly specific analytical methods for the study of differences between normal and pre-eclamptic placentae are close to identifying specific indicators of disease, which may allow early diagnosis and intervention and reveal targets against which therapeutic agents can be developed.

Adult↗

Flap prefabrication - the bridge between conventional flaps and tissue-engineered flaps.

Flap prefabrication is one of the most exciting areas in Plastic Surgery because of its bridging role between conventional reconstructive surgery and tissue engineering. Using this technique,tissues such as bone, cartilage, skin and muscle can be preassembled to form precise composites that will fit any defect. In pre-lamination, for example, an ear may be created by burying cartilage underneath forearm skin and later harvested as a skin-cartilage composite free flap to replace the missing part. Vascular induction is yet another means of customising flaps where new blood supply is introduced to create transplantable tissue. For example, bone chips wrapped in avascular carrier such as muscle can become vascularised grafts. Our experiment describes jejunal prefabrication in a rat model using the same technique. Intestinal segments wrapped in muscle flaps become independent of their mesenteric blood supply by "parasitising" on the muscle's blood supply. This idea arose from our initial observations that intestinal segments transferred to the neck to reconstruct the oesophagus could survive accidental disruption of the pedicle if sufficient time had elapsed. Clearly, the bowel had picked up new blood supply from its bed. Subsequently, jejunal prefabrication was used to reconstruct the oesophagus in a patient in whom there were no recipient vessels for free jejunal transfer. The pedicled latissimus dorsi muscle flap was used as a carrier for the jejunum. Another application of this idea could be in the area of allogeneic trachea or pancreatic transplantation, since present-day techniques have yet to overcome problems such as insufficient vascularity and unpredictable transplant survival. Future applications incorporating biomaterials and cultured cells will usher in the era of tissue-engineered flaps.

Animals↗

The mechanism of hypoglycemic action of the semi-purified fractions of Averrhoa bilimbi in streptozotocin-diabetic rats.

In the present study, we have examined the possible mechanism of the hypoglycemic action of the semi-purified fractions of an ethanolic extract of Averrhoa bilimbi Linn (Oxalidaceae) leaves (ABe) in streptozotocin-diabetic male Sprague-Dawley (SD) rats. The ABe was partitioned with water and butanol to yield a butanol-soluble fraction (BuF) and a water-soluble fraction (AF). The AF was further partitioned with ethyl acetate and hexane to obtain ethyl acetate (EF) and hexane (HF) soluble fractions. The hypoglycemic property of each fraction was assessed by the oral glucose tolerance test (OGTT) at a dose of 125-mg/kg-body weight in streptozotocin (STZ)-diabetic rats (STZ 60 mg/kg i.p.). Fractions AF, BuF and the reference drug metformin (500 mg/kg body weight), produced significant blood glucose-lowering effect in the diabetic rats when compared to the vehicle (distilled water). In the long-term study, the diabetic rats were randomly divided into 4 groups and treated orally by gavage with vehicle, AF (125 mg/kg body weight), BuF (125 mg/kg body weight), and metformin (500 mg/kg body weight) respectively twice a day for 14 days. On day 7 and day 14, AF and BuF, like the reference drug, metformin, lowered the fasting blood glucose concentration significantly (P < 0.05) when compared with the vehicle. The serum insulin level was significantly increased in the AF-treated rats only on day 14 when compared to that in the vehicle-treated rats on day zero (P < 0.05). The serum insulin level in BuF-treated rats was also significantly higher (P < 0.05) on both day 7 and day 14 compared to that on day zero. Hepatic glucose-6-phosphatase activity was significantly lower (P<0.05) in AF- and metformin-treated groups, but not in BuF-treated groups, compared to that in vehicle-treated group. However, there was no change in hepatic glycogen content in AF-, BuF- and metformin-treated group compared to the vehicle-treated group. These results indicate that AF is more potent than BuF in the amelioration of hyperglycemia in STZ-diabetic rats and is a potential source for the isolation of new orally active agent(s) for anti-diabetic therapy.

Animals↗

Mimicking lip features in free-flap reconstruction of lip defects.

This paper introduces a technique of lip reconstruction using free flaps in which recognisable landmarks are mimicked by strategic placement of flap junctions. The technique was applied in 15 patients undergoing reconstruction of combined cheek and lip defects using single (n= 9) or double (n= 6) free flaps. Attention to flap design and strategic placement of flap junctions successfully created the vermilion-cutaneous junction, oral commissure and labiomental groove. The presence of these distinguishing features improved the appearance of the reconstructed lip.

Adult↗

Repair of composite zygomatico-maxillary defects with free bone grafts and free vascularized tissue transfer.

INTRODUCTION: Three-dimensional repair of the zygomatico-maxillary defect calls for an elaborate technique to achieve facial symmetry and correct globe position. We present a technique, which combines the use of a free vascularized soft tissue flap and free bone grafts for repair of composite zygomatico-maxillary defects. PATIENTS: Three patients that underwent radical resection of the maxilla and the zygoma have undergone facial reconstruction using this technique. The mean follow up was 9 months. METHODS: The key points of this technique are: (1) precise reconstruction of the zygomatico-maxillary complex including the orbit; (2) creation of a skeletal framework for canthopexy and suspension of the free flap; (3) repair of through-and-through soft tissue defects with a folded musculocutaneous free flap; and (4) simultaneous harvesting and reconstruction using two surgical teams to reduce the duration of surgery. RESULTS: Reconstruction of the zygomatico-maxillary complex could be successfully accomplished in a single surgical procedure. CONCLUSION: This paper presents a method of repairing zygomatico-maxillary defects with free bone grafts and vascularized soft tissue. However, this concept has yet to be reviewed in the long term.

Aged↗

Digital replantations including fingertip and ring avulsion.

To reduce ischemic time and yet achieve a high-quality repair, the replantation team should be well organized. The team should be conversant with microvascular techniques and employ efficient methods of tendon repair and bone fixation. Developments in instrumentation and technique in recent years have improved success rates and consequently enlarged the indications for replantation surgery. Nevertheless, the economics of care and long-term functional outcome should not be overlooked, and these issues remain unresolved in the replantation versus terminalization question. The authors address topics relevant to replantation, including techniques and complications of digital replantation, ring avulsion injuries, and distal replantation.

Amputation, Traumatic↗

Lipid peroxidation in small and large phospholipid unilamellar vesicles induced by water-soluble free radical sources.

The susceptibility of small and large egg yolk phosphatidylcholine unilamellar vesicles to Fe(2+)/histidine-Fe(3+)- and Fenton reagent (Fe(2+)-H(2)O(2))-induced lipid peroxidation was evaluated by measuring the formation of thiobarbituric acid reactive substances (TBARS). It has been found that surface curvature or phospholipid packing exerts significant effect on the oxidative susceptibility of the unsaturated lipid bilayers and the highly curved and loosely packed small unilamellar vesicles (SUVs) exhibit much less resistance to the oxidative stress induced by the water-soluble free radical sources. The presence of lipid hydroperoxides in sonicated vesicles was excluded as the cause for higher level of lipid peroxidation in the phospholipid SUVs. Instead, the experimental results can be explained by the difference in ability of the water-soluble oxidants to penetrate the two types of lipid membranes. This hypothesis is supported by data obtained from fluorescence lifetime and quenching studies.

Animals↗

The mechanism underlying the hypocholesterolaemic activity of aqueous celery extract, its butanol and aqueous fractions in genetically hypercholesterolaemic RICO rats.

Drinking aqueous celery extract for 8 weeks caused a significant reduction in serum total cholesterol (TC) level in growing genetically hypercholesterolaemic (RICO) rats. In addition, administration of butanol fraction (Fbu) and aqueous fraction (Faq) of celery extract for 7 days by intraperitoneal (i.p.) infusion effectively decreased the serum TC and high-density lipoprotein cholesterol (HDL-C) levels of adult RICO rats. The 8-week study showed that oral intake of celery extract could enhance the 14C-cholesterol/metabolites excretion. The liver and small intestinal sterol synthesis were not affected. Also, long term drinking of aqueous celery extract did not lead to any undesirable side effects on liver functions. The Fbu and Faq lowered serum TC level mainly through increased bile acid excretion but not by modulating the activity of the rate-limiting enzyme for cholesterol biosynthesis, HMG-CoA reductase. Hence, the mechanism elucidated supports that suggested by the 8-week study. A preliminary chemical characterisation of Fbu and Faq fractions by thin layer chromatography (TLC) showed the presence of sugars and amino acids. There is a possibility that polar compounds with sugar or amino acid side chains(s) could contribute to the hypocholesterolaemic action of celery extract.

Alanine Transaminase↗

Effects of cis-unsaturated fatty acids on doxorubicin sensitivity in P388/DOX resistant and P388 parental cell lines.

It has been reported that several cis-unsaturated fatty acids (c-UFAs) could increase doxorubicin (DOX) accumulation in cancer cells and hence elevate its cytotoxicity. However, some researchers showed that c-UFA pretreatment did not affect its cytotoxicity in special cell lines. It is possible that the different results occurred due to different cellular characteristics. We hypothesized that c-UFA treatment might modulate the activities of some antioxidant enzymes to affect the resistance of cells to DOX. In the present study, we examined how c-UFA pretreatment affected DOX cytotoxicity on mouse leukemia cell line, P388, and its resistant subline, P388/DOX, which we found to have significantly higher glutathione peroxidase (GPx) activity as well as P-glycoprotein (p-gp) overexpression. We chose two c-UFAs, gamma-linolenic acid (GLA) (18:3n-6) and docosahexaenoic acid (DHA) (22:6n-3). Cytotoxicity was measured by MTT (3-(4.5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) and trypan blue exclusion assays. DOX accumulation and p-gp expression were measured by flow cytometry. The activities of catalase (CAT), superoxide dismutase (SOD), glutathione S-transferase (GST), and GPx were determined for both cell lines with and without treatment with GLA or DHA. Significant DOX accumulation occurred in both cell lines with GLA or DHA pretreatment, but without any change in p-gp expression in either cell line. Sensitivity to DOX cytotoxicity was improved by GLA or DHA pretreatment in P388/DOX in which only SOD activity was significantly increased, but not in the parental cell line P388 in which both SOD and CAT were significantly increased by the pretreatment. However, combined pretreatment of GLA or DHA with antioxidants, pyrrolidinedithiocarbamate (PDTC) or Vitamin C, could sensitize not only P388/DOX but also P388 cells to DOX. We conclude that the effects of c-UFA pretreatment on the sensitivity of cancer cells to DOX not only depend on the change in drug accumulation but also the change in the levels of antioxidant enzyme activities, and suggest that combined administration of c-UFAs, antioxidants, and DOX may be more effective in treating leukemia.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

Effects of Averrhoa bilimbi leaf extract on blood glucose and lipids in streptozotocin-diabetic rats.

The present study was designed to investigate the hypoglycemic and hypolipidemic activities of an ethanolic extract of Averrhoa bilimbi Linn. leaves (Oxalidaceae, Common name: Bilimbi) in streptozotocin (STZ)-diabetic rats. The optimal hypoglycemic dose (125 mg kg(-1)) was determined by performing the oral glucose tolerance test (OGTT) in both normal and STZ-diabetic rats. To investigate the effect of repeated administration of an ethanolic extract of Averrhoa bilimbi (ABe) leaves, diabetic rats were treated with vehicle (distilled water), ABe (125 mg kg(-1)) or metformin (500 mg kg(-1)) twice a day for 2 weeks. Like metformin, ABe significantly lowered blood glucose by 50% and blood triglyceride by 130% when compared with the vehicle. ABe also significantly increased the HDL-cholesterol concentrations by 60% compared with the vehicle. ABe thus significantly increased the anti-atherogenic index and HDL-cholesterol/total cholesterol ratio. However, like metformin, ABe did not affect total cholesterol and LDL-cholesterol concentrations, but significantly reduced the kidney lipid peroxidation level. These data show that ABe has hypoglycemic, hypotriglyceridemic, anti-lipid peroxidative and anti-atherogenic properties in STZ-diabetic rats.

Animals↗

Cytotoxic and immunopotentiating effects of ethanolic extract of Nigella sativa L. seeds.

In-vitro cytotoxic screening of extracts of Nigella sativa L. seeds (Ranunculaceae) indicated cytotoxicity in the ethyl-acetate fraction (EAF) against different classes of cancer cell lines, P388, Molt4, Wehi 164, LL/2, Hep G2, SW620 and J82, as measured by 3-(4, 5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The ethyl-acetate column chromatographic fraction (CC-5) showed selectivity against Hep G2, Molt4, and LL/2. CC-5 was relatively non-toxic against human umbilical cord endothelial cells at 50 microg/ml. CC-5 had no stimulatory effect on mouse splenocytes as such. CC-5 and water fraction, however, enhanced the proliferative response in the presence of ConA (3 microg/ml), but not LPS (1 and 6 microg/ml). These data indicate that CC-5 possesses a potent cytotoxic effect as well as a potentiating effect on the cellular immune response. The mechanism whereby it produces this needs to be resolved.

Adjuvants, Immunologic↗