Astaxanthin, a natural antioxidant, lowers cholesterol and markers of cardiovascular risk in individuals with prediabetes and dyslipidaemia.

AIM: To determine the effects of astaxanthin treatment on lipids, cardiovascular disease (CVD) markers, glucose tolerance, insulin action and inflammation in individuals with prediabetes and dyslipidaemia. MATERIALS AND METHODS: Adult participants with dyslipidaemia and prediabetes (n = 34) underwent baseline blood draw, an oral glucose tolerance test and a one-step hyperinsulinaemic-euglycaemic clamp. They were then randomized (n = 22 treated, 12 placebo) to receive astaxanthin 12 mg daily or placebo for 24 weeks. Baseline studies were repeated after 12 and 24 weeks of therapy. RESULTS: After 24 weeks, astaxanthin treatment significantly decreased low-density lipoprotein (-0.33 ± 0.11 mM) and total cholesterol (-0.30 ± 0.14 mM) (both P < .05). Astaxanthin also reduced levels of the CVD risk markers fibrinogen (-473 ± 210 ng/mL), L-selectin (-0.08 ± 0.03 ng/mL) and fetuin-A (-10.3 ± 3.6 ng/mL) (all P < .05). While the effects of astaxanthin treatment did not reach statistical significance, there were trends toward improvements in the primary outcome measure, insulin-stimulated, whole-body glucose disposal (+0.52 ± 0.37 mg/m2 /min, P = .078), as well as fasting [insulin] (-5.6 ± 8.4 pM, P = .097) and HOMA2-IR (-0.31 ± 0.16, P = .060), suggesting improved insulin action. No consistent significant differences from baseline were observed for any of these outcomes in the placebo group. Astaxanthin was safe and well tolerated with no clinically significant adverse events. CONCLUSIONS: Although the primary endpoint did not meet the prespecified significance level, these data suggest that astaxanthin is a safe over-the-counter supplement that improves lipid profiles and markers of CVD risk in individuals with prediabetes and dyslipidaemia.

Ultra high-Performance Liquid Chromatography (UHPLC) method development and validation for the identification of oxidized product of Epigallocatechin-3-Gallate (EGCG).

OBJECTIVE: In the present study we reported oxidation of epigallocatechin-3-gallate (EGCG) and validation of oxidized product by a validated ultra high-performance liquid chromatography (UHPLC) method. METHODS: Two hundred milligrams of EGCG was oxidized in 5 mL of hydrogen peroxide (H2O2) and was identified by a validated UHPLC method with precision and robustness. Confirmation of parameters like C-H stretching and mass was carried out using infrared spectroscopy and mass spectroscopy, respectively. Identification of oxidized EGCG (O-EGCG) was done by UHPLC. RESULTS: The infrared spectroscopy chromatograms observed less intensity C-H stretching as compared to O-EGCG. The mass of EGCG and O-EGCG were 459.09 and 915.16, respectively. Structure elucidation revealed a loss of one proton in O-EGCG as compared to EGCG. Validation of the developed method was specific, with linear correlation coefficient 0.9981 and 0.9917, respectively for EGCG and O-EGCG, the accuracy rate of 95.2%-99.6% for EGCG, and 99.18%-101.5% for O-EGCG. CONCLUSION: Together, the results of this study demonstrate the formation of a dimer also the UHPLC method developed for identification of both EGCG and O-EGCG is validated as per the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) guidelines.

Role of High Magnification Using Operative Microscope in Surgical Clearance of Glomus Tumor in Distal Phalanx: An Experience of 13 Cases.

Background: Glomus because of their small size in fingers presents difficulty in clear visualization in the operation theater and requires magnifying techniques. Because of the dearth of infrastructure in many hospitals, the excision of these is done with either no or inadequate magnification. Magnetic resonance imaging (MRI) has become the gold standard investigation as glomus tumors can be visualized on radiology very clearly. The reason for recurrence given in the literature is access to tumors by the type of surgical approach for clear visualization, but high magnification being the most important, as the size of glomus is very small has no or limited mention in the literature. Being in a tertiary care hospital, we have analyzed the role of high magnification in the excision of glomus and its impact on recurrence as the end outcome. Aim: To understand the role of intraoperative high magnification using operative microscope and its advantages in the surgical clearance of glomus tumor of fingers. Settings and Design: Retrospective record review. Materials and Methods: Thirteen cases of glomus tumor in the phalanges over a period of 7 years were operated under operative microscope with a magnification ranging from 10× to 12.5×; data and mean follow-up to 5.5 years have been analyzed. Results: Age ranged from 24 to 72 years; all the glomus tumors were in the distal phalanx. Three cases had bony erosion on MRI scan. We had an equal distribution of three cases each in the thumb, ring, and middle finger. Conclusions: (1) High magnification with operative microscope is essential during the excision of glomus tumor especially in the distal phalanx in order to prevent recurrence; (2) advantages of high magnification are clear delineation with complete tumor excision, with meticulous repair of nail bed.

Assessment of Antioxidant, Immunomodulatory Activity of Oxidised Epigallocatechin-3-Gallate (Green Tea Polyphenol) and Its Action on the Main Protease of SARS-CoV-2-An In Vitro and In Silico Approach.

Owing to the instability of Epigallocatechin Gallate (EGCG), it may undergo auto-oxidation and form oxidised products or dimers. In the present study, we aimed to evaluate the therapeutic effects, including antioxidation and immunomodulatory action, of the Oxidised Epigallocatechin Gallate (O-EGCG) as compared to native EGCG and the action of these compounds on main protease (Mpro) docking against SARS-CoV-2. HCT-116 (Human Colon Cancer) cell lines were used to estimate the total antioxidant capacity and lipid peroxidation levels and pro-inflammatory markers (human IL-6, IL-1ß, TNF-α). Further, molecular docking analysis was performed by AutoDock and visualised in Discovery studio. Improved antioxidant capacity of O-EGCG was observed, and there was a significant decrease in the inflammatory markers (IL-1ß, IL-6, and TNF-α) when O-EGCG was applied as compared to EGCG. The O-EGCG was shown to be strongly associated with the highest docking score and active site residues of IL-1, IL-6, and TNF- α, as well as the Mpro of SARS-CoV-2, according to in silico approach. The in vitro and in silico analyses indicate an improved therapeutic action of the oxidised form of EGCG. The effective inhibitory action of O-EGCG against SARS-CoV-2 suggests further exploration of the compound against COVID-19 and its efficacy. However, in vivo studies and understanding of the mechanism of action of O-EGCG may yield a better opinion on the use of O-EGCG and future human clinical trials.

Ultrafine Copper Oxide Particles Dispersed on Nitrogen-Doped Hollow Carbon Nanospheres for Oxidative Esterification of Biomass-Derived 5-Hydroxymethylfurfural.

One-pot synthesis of furan-2,5-dimethylcarboxylate (FDMC) from 5-hydroxymethylfurfural (HMF) is highly demanding for the commercial production of polyethylene furanoate (PEF). Herein, a direct synthesis of FDMC is reported from oxidative esterification of HMF using ultrafine CuO particles dispersed on nitrogen-doped hollow carbon nanospheres (CuO/N-C-HNSs) as a catalyst and tert-butyl hydroperoxide (TBHP) as an oxidizing and methylating reagent. The CuO/N-C-HNSs was prepared through a template protection-sacrifice strategy using SiO2 as a sacrificial template and histidine as the precursor for N and C. N-doping facilitated a strong interaction between the support and copper species, affording formation of CuO nanoparticles of less than 10 nm in size. By virtue of the highly dispersed CuO nanoparticles and a high BET surface area 373 m2 /g, the CuO/N-C-HNSsshows excellent catalytic performance in the selective conversion of HMF into FDMC affording 93 % yield of the desired product with a TON value of 49. Furthermore, the oxidative esterification involving SP3 C-H bond functionalization is also demonstrated using the same catalyst.

Factors determining the outcome of paediatric exotropia surgery.

OBJECTIVE: To determine the socio-demographic and clinical profile of exotropia surgery outcomes amongst paediatric patients. METHODS: This is a descriptive, retrospective, clinical study of surgeries performed between 2014 and 2016 at the Sarawak Heart Centre, Malaysia. Medical records of patients with primary and secondary exotropia were reviewed. The following factors that affected the surgical outcomes were collected: onset age of squint, age at the time of surgery, the interval between diagnosis and surgery, the type of exotropia, visual acuity, presence of amblyopia, previous patching, anisometropia, refractive error, type of surgery, preoperative and postoperative deviation, pre-existing ocular comorbidity and systemic illness. RESULT: A total of 15 patients were studied with more than two thirds being females. Seven patients had primary exotropia while eight patients had secondary exotropia. Average interval between diagnosis and surgery was 1.3 years (±0.82) for primary exotropia and 1.2 years (±0.84) for secondary exotropia. Average pre-operative angle for primary exotropia was 50.57PD (±10.83) whereas secondary exotropia was 39.38PD (±8.63). Seven patients had successful surgical outcomes of within 10 prism dioptres, five for primary exotropia and two for secondary exotropia. The response to surgery was 3.0PD/mm (±0.59) for primary exotropia and 2.2PD/mm (±0.74) for secondary exotropia. CONCLUSION: In our study, primary exotropia had larger preoperative angle than secondary exotropia. The response to surgery was positively correlated with the preoperative angle of deviation. Primary exotropia showed better surgical outcome.

Altered Myokine Secretion Is an Intrinsic Property of Skeletal Muscle in Type 2 Diabetes.

Skeletal muscle secretes factors, termed myokines. We employed differentiated human skeletal muscle cells (hSMC) cultured from Type 2 diabetic (T2D) and non-diabetic (ND) subjects to investigate the impact of T2D on myokine secretion. Following 24 hours of culture concentrations of selected myokines were determined to range over 4 orders of magnitude. T2D hSMC released increased amounts of IL6, IL8, IL15, TNFa, Growth Related Oncogene (GRO)a, monocyte chemotactic protein (MCP)-1, and follistatin compared to ND myotubes. T2D and ND hSMC secreted similar levels of IL1ß and vascular endothelial growth factor (VEGF). Treatment with the inflammatory agents lipopolysaccharide (LPS) or palmitate augmented the secretion of many myokines including: GROa, IL6, IL8, IL15, and TNFa, but did not consistently alter the protein content and/or phosphorylation of IkBa, p44/42 MAPK, p38 MAPK, c-Jun N-terminal kinase (JNK) and NF-kB, nor lead to consistent changes in basal and insulin-stimulated glucose uptake or free fatty acid oxidation. Conversely, treatment with pioglitazone or oleate resulted in modest reductions in the secretion of several myokines. Our results demonstrate that altered secretion of a number of myokines is an intrinsic property of skeletal muscle in T2D, suggesting a putative role of myokines in the response of skeletal muscle to T2D.

Excessive secretion of IL-8 by skeletal muscle in type 2 diabetes impairs tube growth: potential role of PI3K and the Tie2 receptor.

Reduced capillary density is a feature of skeletal muscle (SkM) in type 2 diabetes (T2D), which is associated with multiple metabolic and functional abnormalities. SkM has been identified as a secretory tissue, releasing myokines that regulate multiple processes, including vascularization. We sought to determine how myokines secreted from T2D myotubes might influence SkM angiogenesis. Conditioned media (CM) were generated by myotubes from T2D and nondiabetic (ND) subjects. Primary human endothelial cells (HUVEC) and SkM explants were exposed to CM or recombinant myokines, and tube number or capillary outgrowth was determined as well as measurement of protein expression and phosphorylation. CM from ND myotubes stimulated tube formation of HUVEC to a greater extent than T2D myotubes (T2D-CM = 100%, ND-CM = 288 ± 90% after 48 h, P < 0.05). The effects of T2D myotube CM were mediated by IL-8, not IL-15 or GROα, and were due not to cell damage but rather through regulating tube production and maintenance (response to T2D-IL-8 = 100%, response to ND-IL-8 = 263 ± 46% after 48 h, P < 0.05). A similar effect was seen in SkM explants with exposure to IL-8. The dose-dependent effect of IL-8 on tube formation was also observable in the PI3K and FAK signaling pathways and mediated at least in part by PI3K, leading to regulation of Tie2 expression. These results suggest that elevated levels of IL-8 secreted from T2D myotubes create a muscle microenvironment that supports reduced capillarization in T2D. Impaired vascularization of SkM limits the availability of substrates, including glucose and contributes to the T2D phenotype.

Surgical treatment of children with raised intra ocular pressures associated with sturge weber syndrome at hospital kuala lumpur, malaysia.

No abstract available.

Naringin ameliorates gentamicin-induced nephrotoxicity and associated mitochondrial dysfunction, apoptosis and inflammation in rats: possible mechanism of nephroprotection.

Gentamicin-induced nephrotoxicity has been well documented, although its underlying mechanisms and preventive strategies remain to be investigated. The present study was designed to investigate the protective effect of naringin, a bioflavonoid, on gentamicin-induced nephrotoxicity and to elucidate the potential mechanism. Serum specific renal function parameters (blood urea nitrogen and creatinine) and histopathology of kidney tissues were evaluated to assess the gentamicin-induced nephrotoxicity. Renal oxidative stress (lipid peroxidation, protein carbonylation, enzymatic and non-enzymatic antioxidants), inflammatory (NF-kB [p65], TNF-α, IL-6 and MPO) and apoptotic (caspase 3, caspase 9, Bax, Bcl-2, p53 and DNA fragmentation) markers were also evaluated. Significant decrease in mitochondrial NADH dehydrogenase, succinate dehydrogenase, cytochrome c oxidase and mitochondrial redox activity indicated the gentamicin-induced mitochondrial dysfunction. Naringin (100mg/kg) treatment along with gentamicin restored the mitochondrial function and increased the renal endogenous antioxidant status. Gentamicin induced increased renal inflammatory cytokines (TNF-α and IL-6), nuclear protein expression of NF-κB (p65) and NF-κB-DNA binding activity and myeloperoxidase (MPO) activity were significantly decreased upon naringin treatment. In addition, naringin treatment significantly decreased the amount of cleaved caspase 3, Bax, and p53 protein expression and increased the Bcl-2 protein expression. Naringin treatment also ameliorated the extent of histologic injury and reduced inflammatory infiltration in renal tubules. U-HPLS-MS data revealed that naringin co-administration along with gentamicin did not alter the renal uptake and/or accumulation of gentamicin in kidney tissues. These findings suggest that naringin treatment attenuates renal dysfunction and structural damage through the reduction of oxidative stress, mitochondrial dysfunction, inflammation and apoptosis in the kidney.

Inflammatory cytokines and chemokines, skeletal muscle and polycystic ovary syndrome: effects of pioglitazone and metformin treatment.

OBJECTIVE: Chronic low-grade inflammation is a common feature of insulin resistant states, including obesity and type 2 diabetes. Less is known about inflammation in Polycystic Ovary Syndrome (PCOS). Thus we evaluated the impact of PCOS on circulating cytokine levels and the effects of anti-diabetic therapies on insulin action, cytokine and chemokine levels and inflammatory signaling in skeletal muscle. METHODS: Twenty subjects with PCOS and 12 healthy normal cycling (NC) subjects of similar body mass index were studied. PCOS subjects received oral placebo or pioglitazone, 45 mg/d, for 6 months. All PCOS subjects then had metformin, 2 g/day, added to their treatment. Circulating levels of cytokines, chemokines, and adiponectin, skeletal muscle markers of inflammation and phosphorylation of signaling proteins, insulin action evaluated by the hyperinsulinemic/euglycemic clamp procedure and Homeostasis Model Assessment of Insulin Resistance were measured. RESULTS: Circulating levels of a number of cytokines and chemokines were generally similar between PCOS and NC subjects. Levels in PCOS subjects were not altered by pioglitazone or metformin treatment, even though whole body insulin action and adiponectin levels increased with pioglitazone. In spite of the lack of change in levels of cytokines and chemokines, several markers of inflammation in skeletal muscle were improved with Pio treatment. CONCLUSIONS: PCOS may represent a state of elevated sensitivity of inflammatory cells in skeletal muscle to cytokines and chemokines, a property that could be reversed by pioglitazone treatment together with improved insulin action.

Ultrasonographic findings in eyes with retinopathy of prematurity in malaysia.

RetCam is an excellent screening tool for the detection of retinopathy of prematurity (ROP). However, affordability is a barrier when adopting the use of RetCam in developing countries. We aimed to describe different stages of ROP using ultrasonographic B-scan and to evaluate the association between funduscopic examinations and ultrasonographic B-scan findings in premature neonates with ROP in Malaysia. A descriptive cross sectional study was conducted in 90 eyes of 47 premature neonates with different stages of ROP in three tertiary hospitals in Malaysia. Experienced ophthalmologists performed detailed funduscopic examinations using binocular indirect ophthalmoscopy (BIO). A masked examiner performed a 10 MHz ultrasonographic B-scan evaluation with 12 meridian position images within 48 hours of clinical diagnosis. Data from the clinical examination and ultrasonographic findings were collected and analysed. We recruited 37 eyes (41.1%) with stage 1 ROP, 29 eyes (32.3%) with stage 2, 18 eyes (20.0%) with stage 3, and 3 eyes (3.3%) with stages 4 and 5 based on the clinical assessment. Ultrasonography correctly identified 3 (8.1%) stage 1 eyes, 17 (58.6%) stage 2 eyes, 13 (72.2%) stage 3 eyes, and 3 each (100%) of the stage 4 and 5 eyes. There was a significant association between the funduscopic signs and the ultrasound findings for stage 2 ROP and above (Fisher's exact test, p <0.001). In conclusion, all stages of ROP were detected and described with a 10 MHz ultrasonic B-scan system. A significant association was observed between funduscopic signs and ultrasonographic findings in premature Malaysian neonates with stage 2 ROP and above.

Tay-Sach disease with "cherry-red spot"--first reported case in Malaysia.

We present a rare case of Tay-Sachs disease with retinal 'cherry-red spots' in a 19-month-old Malay child. Molecular genetic studies confirmed the diagnosis. The case highlights that 'cherry-red spot' is a useful clinical clue in Tay-Sachs disease and several other lysosomal storage disorders. It serves as an ideal illustration of the eye as a window to inborn error of metabolism.

Rosai-Dorfman disease--perianaesthetic concerns.

Rosai-Dorfman Disease (RDD) may be challenging for anesthesiologist in view of its multisystem involvement, specially the airway. We present a patient with RDD scheduled for bilateral rhinotomy and bilateral neck dissection for nasal obstruction and gross bilateral lymphadenopathy. Care should be taken in airway management because of the distortion of airway anatomy by the soft tissue mass with possible intracheal extension of mass. Central venous catheterization should be guided by ultrasonography.

Retinoblastoma Registry report--Hospital Kuala Lumpur experience.

Retinoblastoma is a childhood ocular cancer. The aim of this paper is to describe the clinical and epidemiological characteristics of patients with retinoblastoma in a major paediatric ophthalmology center in the country. Retrospective information was collected through the retinoblastoma registry. Late presentation with advanced staging is a major problem.