Savior of Diabetes: Antioxidants

Introduction: The exposure of humans to antioxidants regulating the process and progress of diabetes mellitus (DM) is of major interest. Several phytoactive compounds such as flavonoids, lignans, prophenylphenols, etc. possess antioxidant property. Antioxidants exert free radical scavenging activity, improve the insulin sensitivity and pancreatic β cell activity, stimulate insulin secretion, and reduce the carbohydrate absorption. Antioxidants also combat complications like diabetic wound healing by increasing the collagen deposition, improving the fibroblasts level, and decreasing the 11-β hydroxydehydrogenase level. They revert the cardiovascular changes of DM by reducing the lipid profile level. Antioxidants also exert their regulatory effect on diabetic nephropathy and peripheral vascular diseases. Body-research methods: The terms “diabetes” or “diabetes mellitus” or type 1 diabetes mellitus” or “type 2 diabetes mellitus” or “hyperglycaemia” or “antioxidant” or “antioxidant” combined with “diabetic complication” were searched in following databases such as PubMed, Web of Science Scopus, and Google Scholar. Conclusion: Understanding the effects of antioxidants against DM is beneficial for disease progress assessment and development of prophylaxis regimens. Although several researches are carried out on antioxidants, current population has still less confidence on them. Hence, more detailed analysis and clinical studies investigating on the underlying mechanisms of antioxidants towards DM are mandatory

Histomorphometric profile of the corneal response to short-term reverse-geometry orthokeratology lens wear in primate corneas: a pilot study

Purpose: To investigate the histological changes in primate cornea induced by short-term overnight orthokeratology (OK). Methods: Nine young adult primates were used. One animal served as negative control. The remaining 8 animals wore reverse-geometry OK lenses for periods of 4, 8, 16, and 24 hours on 1 eye with the other eye as control. Central and midperipheral corneal thickness, as well as ultrastructural changes in corneal epithelium, stroma and endothelium in response to OK lenses, were evaluated. Results: OK significantly reduced the thickness of the central cornea in all treatment groups. The central corneal thinning was both stromal and epithelial in origin. Substantial midperipheral corneal thickening was seen in 16-hour and 24-hour lens-wear groups and this effect was both stromal and epithelial in origin as well. Histology evidence indicated the primary epithelial response in the central cornea was compression of cells that resulted in wing cells becoming shorter and basal cells being squatted rather than lost or migration of cell layers. These pronounced cell shape changes occurred without compromising the structural integrity of the desmosomes. The thickened corneal epithelium has normal cell layers. The squamous cells have larger surface sizes and are composed of oval instead of flattened nuclei. This implied delayed surface cell exfoliation at the thickened midperipheral epithelium. Physical presence of OK lens over the cornea did not influence the microstructures of microvilli and microplicae, endothelium, and collagen distribution. Conclusions: The primate cornea, particularly the corneal epithelium, responds rapidly to the application of reverse-geometry OK lenses with significant epithelial cell shape alterations with short-term OK lens wear. This finding suggests that the corneal epithelium is moldable in response to the physical forces generated by the OK lenses

Oral administration of tocotrienol ameliorates lead-induced toxicity in the rat brain

The occurrence of severe lead (Pb) poisoning has risen in certain countries. There is increasing evidence that chronic lead exposure disturbs the prooxidant: antioxidant balance in the brain tissue and alters brain histology. The present study observed the antioxidant effect of tocotrienol-rich fraction (TRF) on brain tissues of the experimental rats following lead poisoning. Eighteen (n=18) male Sprague-Dawley rats, 6-weeks old, were randomly divided into control (CTRL) group and experimental groups; fed with 0.2% w/v lead acetate, as PB2 group; and fed with 0.2% w/v lead acetate and daily TRF supplementation (200 mg/kg body weight) as PB2T group. The experiment was conducted for 30 days. At the end of the study, the brain tissues were harvested and histopathological changes of the hippocampal region were observed. Biochemical findings such as brain lead, TRF and malondialdehyde (MDA) levels, and erythrocyte superoxide dismutase (SOD) activity were determined. It was observed that atypical apoptotic-like and disorganized neurons were present in the hippocampal region of the untreated PB2 group compared to PB2T group. Biochemical parameters showed a significant decrease (p 0.05) was obtained for MDA level, there was a significant increase (p < 0.05) in the erythrocyte SOD activity in PB2T compared to PB2 and CTRL. Supplementation with TRF improved histopathological changes in the brain tissues caused by lead exposure in drinking water by reducing lead accumulation in the brain of experimental rats

Ketamine-xylazine/tiletamine-zolazepam prolonged anesthesia in Cynomolgus monkeys

The physiological effects of a mixture of ketamine, xylazine, tiletamine and zolazepam (KT/XZ), in cynomolgus monkeys during 24 hr anesthesia is described. Eight were induced with ketamine IM and anesthetized with IV KT/XZ. In all, anesthesia was maintained for 24 hours with large decreases in rectal temperature, heart and respiratory rates but moderate hypotension. All monkeys recovered normally 4 hours post-anesthesia. These results suggest that KX/TZ mixture could be used for prolonged anesthesia in cynomolgus monkeys

Tocotrienol rich fraction supplementation improved lipid profile and oxidative status in healthy older adults: A randomized controlled study

<p>Abstract</p> <p>Background</p> <p>Vitamin E supplements containing tocotrienols are now being recommended for optimum health but its effects are scarcely known. The objective was to determine the effects of Tocotrienol Rich Fraction (TRF) supplementation on lipid profile and oxidative status in healthy older individuals at a dose of 160 mg/day for 6 months.</p> <p>Methods</p> <p>Sixty-two subjects were recruited from two age groups: 35-49 years (n = 31) and above 50 years (n = 31), and randomly assigned to receive either TRF or placebo capsules for six months. Blood samples were obtained at 0, 3^rdand 6^thmonths.</p> <p>Results</p> <p>HDL-cholesterol in the TRF-supplemented group was elevated after 6 months (p < 0.01). Protein carbonyl contents were markedly decreased (p < 0.001), whereas AGE levels were lowered in the > 50 year-old group (p < 0.05). Plasma levels of total vitamin E particularly tocopherols were significantly increased in the TRF-supplemented group after 3 months (p < 0.01). Plasma total tocotrienols were only increased in the > 50 year-old group after receiving 6 months of TRF supplementation. Changes in enzyme activities were only observed in the > 50 year-old group. SOD activity was decreased after 3 (p < 0.05) and 6 (p < 0.05) months of TRF supplementation whereas CAT activity was decreased after 3 (p < 0.01) and 6 (p < 0.05) months in the placebo group. GPx activity was increased at 6 months for both treatment and placebo groups (p < 0.05).</p> <p>Conclusion</p> <p>The observed improvement of plasma cholesterol, AGE and antioxidant vitamin levels as well as the reduced protein damage may indicate a restoration of redox balance after TRF supplementation, particularly in individuals over 50 years of age.</p

Mutations in KIF27, GNAS and IFT140 genes in a patient with VACTERL association: a case report

VACTERL association is a rare genetic disorder involving at least three of the following congenital malformations: vertebral defects (V), anal atresia (A), cardiac defects (C), trachea-oesophageal fistula with or without oesophageal atresia (TE), renal anomalies (R) and limb abnormalities (L). Until now, the aetiology of VACTERL association is unknown, particularly at the molecular level. Here, we performed whole exome sequencing (WES) of an infant with VACTERL association. The patient was delivered prematurely at 30 weeks and had 4/6 of the VACTERL malformations. Trio-WES analysis was performed using Torrent Suite and ANNOVAR. Polymorphisms with an allele frequency of >0.01 were excluded, and the remaining variants were filtered based on de novo mutations, autosomal recessive, X-linked and di-genic inheritance traits. In this patient, no homozygous, compound heterozygous or X-linked mutations was associated with VACTERL. However, we identified two heterozygous mutations; KIF27 (ENST00000297814: c.3004A> C:p.N1002H) and GNAS (ENST00000371098: c.205C>A:p.H69N) genes that were inherited from her father and mother respectively. A de novo, IFT140 gene mutation (ENST00000426508: c.683C>G:p.S228C) was also identified in this patient. The VACTERL phenotype in this patient may due to heterozygous mutations affecting KIF27 and GNAS genes, inherited via autosomal recessive trait. In addition, the IFT140 gene mutation may also be involved. These genes are known to be directly or non-directly involved in the sonic hedgehog signalling that is known to be implicated in VACTERL. This is the first report of these genetic mutations in association with VACTERL

Preliminary study shows novel variant detected in the screening of RET gene in Malaysian patients with Hirschsprung’s disease

Hirschsprung’s disease (HSCR) is a disorder associated with congenital absence of ganglion cells in the gastrointestinal tract. Molecular analyses have identified variants in various genes including RET, GDNF, EDN3 and EDNRB that are involved in the development, migration and survival of neural cells. Variants in the receptor tyrosine kinase (RET) are most common and have been identified in 10-20% of sporadic HSCR patients. The objective of this study was to screen for RET gene variants in Malaysian patients with HSCR. Thirty-two patients with HSCR and 30 normal controls were recruited for this study. Mutations were screened using the Polymerase Chain Reaction – Denaturing High Performance Liquid Chromatography (PCR-dHPLC) approach. Mutations identified were then confirmed using Sanger sequencing. We identified one novel rare variant in exon 4 (A268A c807 G>C) in one patient. We also identified the common coding sequence variantsA45A (c135G>A), A432A (c1296A>G), L769L (c2307 T>G) and the G691S in our cohort of patients. In conclusion, our Malaysian patients with HSCR diseases showed the presence of similar RET gene common variants which have been described in other populations. We have also identified a novel variant in exon 4 (A268A)

UKM medical graduates’ perception of their communication skills during housemanship

The art of talking to patients and their relatives does not come naturally to most of us and the ability to put oneself in the patients’ predicament is difficult particularly for the young doctors. To identify the communication abilities of the young doctors, a cross sectional study was carried out on 32 house officers who graduated from UKM in 2004 during their house jobs at different hospitals in Malaysia. A standardized questionnaire was used to collect the data. Fifty nine percent respondents claimed that they had communicated very well with patients while 69% with support staff and 88% with peers. On the other hand 38% and 41% of the respondents claimed they communicated very well with their superiors and families of patients. Only 22% of the graduates’ skills of communication in breaking bad news were very well, while 50% and 81% were very well in counselling patients and taking consent for procedures. Curriculum planners need to emphasize the importance of developing good communication skills in all aspects for the future doctor

Evaluation of Topical Tocopherol Cream on Cutaneous Wound Healing in Streptozotocin-Induced Diabetic Rats

Diabetes is a common cause of delayed wound healing. The aim of the study was to determine the effect of topical administration of tocopherol cream on the wound healing process in diabetic rats. The study was conducted using 18 male Sprague Dawley rats which were divided into three groups: (I) diabetic rats receiving control cream , (II) diabetic rats receiving 0.06% tocopherol cream , and (III) diabetic rats receiving 0.29% tocopherol cream . Four cutaneous wounds were created at the dorsal region of the rats. Wound healing was assessed by total protein content, rate of wound closure estimation, and histological studies on the tenth day after wounding. Tocopherol treatment enhanced the wound healing process by increasing rate of wound closure and total protein content significantly compared to the control group. Histological observation also showed better organized epithelium and more collagen fibers in the tocopherol treated groups. Application of tocopherol cream enhances wound healing process in diabetic condition which is known to cause delay in wound healing