Volume 31, Issue 2

Diabetes mellitus (DM) is a group of metabolic diseases related to the dysfunction of insulin, causing hyperglycaemia and life-threatening complications. Current early screening and diagnostic tests for DM are based on changes in glucose levels and autoantibody detection. This review evaluates recent studies on biomarker candidates in diagnosing type 1, type 2 and gestational DM based on omics classification, whilst highlighting the relationship of these biomarkers with the development of diabetes, diagnostic accuracy, challenges and future prospects. In addition, it also focuses on possible non-invasive biomarker candidates besides common blood biomarkers.

Mild cognitive impairment (MCI) is a modifiable risk factor in progression of several diseases including dementia and type 2 diabetes. If cognitive impairments are not reversed at an early stage of appearance of symptoms, then the prolonged pathogenesis can lead to dementia and Alzheimer’s disease (AD). Therefore, it is necessary to detect the risk factors and mechanism of prevention of cognitive dysfunction at an early stage of disease. Poor lifestyle, age, hyperglycemia, hypercholesterolemia, and inflammation are some of the major risk factors that contribute to cognitive and memory impairments in diabetic patients. Mild cognitive impairment was seen in those individuals of type 2 diabetes, who are on an unhealthy diet. Physical inactivity, frequent alcohol consumptions, and use of packed food products that provides an excess of cheap calories are found associated with cognitive impairment and depression in diabetic patients. Omega fatty acids (FAs) and polyphenol-rich foods, especially flavonoids, can reduce the bad effects of an unhealthy lifestyle; therefore, the consumption of omega FAs and flavonoids may be beneficial in maintaining normal cognitive function. These functional foods may improve cognitive functions by targeting many enzymes and molecules in cells chiefly through their anti-inflammatory, antioxidant, or signaling actions. Here, we provide the current concepts on the risk factors of cognitive impairments in type 2 diabetes and the mechanism of prevention, using omega FAs and bioactive compounds obtained from fruits and vegetables. The knowledge derived from such studies may assist physicians in managing the health care of patients with cognitive difficulties.

Magnesium (Mg 2+ ) is one of the major elements required to maintain normal metabolism and ionic balances in ocular tissues. The physiological role of Mg 2+ is mediated through maintaining the Na + -K + -ATPase on membrane, favoring energy-generating reactions, replication of DNA and protein synthesis. Despite the wide availability of this element, hypomagnesemia has been associated with many human ailments. Recent studies highlighted the association of hypomagnesemia and, thereby, supplementation of Mg 2+ in the management of eye diseases. Glaucoma, senile cataract and diabetic retinopathy were associated with low level of extracellular Mg 2+ . The neurovascular protective effects of Mg 2+ mediated through activation of endothelial nitric oxide synthase and inhibition of endothelin-1 eventually result in vasodilatation of retinal vessels. Mg 2+ can maintain the lens sodium pump activity and antioxidant status and block the calcium channels and release of glutamate in nerve endings. Furthermore, it can prevent the apoptosis of retinal ganglion cells. All these effects contribute to its being a pharmacological agent against ocular diseases. However, clinical trials are scant. This article discusses the role of Mg 2+ as a possible therapeutic agent in the management of glaucoma, cataract and diabetic retinopathy.

Background Migraine is a multifaceted chronic disease with common ocular symptoms. Habituation is the decremental response on repeated stimulations. The literature review indicates controversial results regarding habituation in migraine individuals. The present study aimed to compare the habituation response using visual evoked potential (VEP) measures among migraine and control subjects. Methods This was a cross-sectional study performed among migraine individuals attending the Department of Medicine and Neurology, of the age group of 18–30 years at Sri Manakula Vinayagar Medical College and Hospital, Puducherry. Habituation was evaluated in the two groups, control (n = 40) and migraine (n = 40), using pattern reversal VEP. The recording was done for 15-min duration and divided into four blocks of 3.8 min each. The results were compared employing Student t-test, and p < 0.05 was considered to be statistically significant. Results Our study indicates that latency N75, N145, and P100 amplitude showed significant differences between the two groups. In the right eye, on comparing the first and fourth block P100 amplitude in the migraine group, a significant increase (p < 0.001) was observed in the fourth block. Similarly, in the left eye, the control group showed a significant decrease in the fourth block (p = 0.002), whereas the migraine group showed a significant increase (p < 0.001). Conclusions The present study concludes that migraine individuals report deficient habituation, evaluated using pattern reversal VEP.

Background Hypertension is the major health burden associated with increased cardiovascular morbidity and mortality. Positive family history and stress are the risk factors for hypertension. The present study aims to evaluate the effect of acute stress on the cardiac autonomic modulation in normotensive individuals with parental history of hypertension. Methods Sixty healthy male volunteers (30 with parental history of hypertension-NTPH+ group and 30 without parental history of hypertension-NTPH− group) in the age group of 18–24 years were included in the study. Short-term baseline heart rate variability (HRV) evaluation was done in frequency domain. Volunteers performed mental arithmetic stress task (MAST). HRV was measured before MAST, during MAST, and recovery period. HRV in both groups were compared. Results Analysis showed a significant increase in heart rate (p-value = 0.038) and systolic blood pressure (p-value = 0.01) in NTPH+ group compared to the NTPH− during MAST. NTPH+ group showed significantly higher LFnu (p-value = 0.03) and LF/HF ratio (p-value = 0.02) during MAST. Reduction in HFnu (p-value = 0.027) was significantly higher in the study group. ANOVA analysis demonstrated significant increase in LFnu [F(2.602, 75.46) = 18.60; p < 0.001; ηp2 = 0.391] and LF/HF ratio [F(1.76, 51.043) = 29.952; p < 0.001; ηp2 = 0.508] during MAST and 10 min of recovery period from baseline value in NTPH+ group. HFnu has significantly reduced during MAST and 5 min recovery period from baseline value in NTPH+ group [F(2.78, 80.72) = 12.77; p = 0.033, ηp2 = 0.28]. Conclusions Acute mental stress leads to exaggerated sympathetic response and vagal suppression in healthy individuals with parental history of HTN. This study concludes that HRV, which reflects autonomic flexibility, is lower during acute mental stress and post-stress recovery period in normotensive males with parental history of HTN.

Background The aim of this study was to know the present scenario of blood lead level and its effect on serum lipid peroxide and antioxidant parameters of spray painters. Methods We included 42 male spray painters and 50 control subjects with an age range of 20–45 years. Blood lead level, serum lipid peroxide and antioxidant parameters, i.e. erythrocyte catalase, superoxide dismutase (SOD), plasma ceruloplasmin, nitric oxide, uric acid and bilirubin, were quantified by standard methods. Results We observed the significant elevated blood lead (p < 0.001, 458%), lipid peroxide (p < 0.001, 170%), uric acid (p < 0.001, 25.6%) and bilirubin (p < 0.01, 24.5%) and the significant decrease in antioxidant enzymes like SOD (p < 0.001, −50.4%), catalase (p < 0.001, −34.33%), ceruloplasmin (p < 0.001, −32.7%) and nitric oxide (p < 0.001, −39.58%) in the study group as compared to control. A significant positive correlation coefficient (r) of blood lead level with lipid peroxide (r = 0.44, p < 0.001), uric acid (r = 0.33 p < 0.05) and bilirubin (r = 0.35, p < 0.05) and a negative correlation with SOD (r = −0.32, p < 0.05), catalase (r = −0.33, p < 0.05), ceruloplasmin (r = −0.27, p < 0.05) and nitric oxide (r = 0.30, p < 0.05) were observed. Conclusions Elevated blood lead level induces serum lipid peroxide and alters the antioxidant enzymes of spray painters. Therefore, it is necessary to reduce the blood lead level by taking proper precautions while spraying the paints, and additional antioxidant supplementation like vitamin C, multivitamin and multiminerals will be useful in reducing oxidative stress.

Background The ovotoxicity of 4-vinylcyclohexene diepoxide (VCD) has been established in several experimental models. Hesperidin (HSD) is a bi-flavonoid found in citrus fruits and has been reported to be a potent antioxidant and anti-inflammatory agent. Here, we have evaluated the rescue role of hesperidin on VCD-induced toxicity in the brain, ovary, and uterus of rats. Methods Six groups of rats containing ten rats in each group were orally given corn oil (control), hesperidin (100 mg/kg), hesperidin (200 mg/kg), VCD (250 mg/kg), VCD [(250 mg/kg)+hesperidin (100 mg/kg)] and VCD [(250 mg/kg)+hesperidin (200 mg/kg)] once a day for 30 days, respectively. Thereafter, we determined the selected biomarkers of oxidative damage, inflammation, endocrine balance, and histology of the reproductive organs. Results The data showed that hesperidin rescued VCD-induced increase in oxidative stress (hydrogen peroxide and malondialdehyde) and inflammatory (nitric oxide) biomarkers. In addition, hesperidin restored the reduction in antioxidant enzymes (catalase, glutathione S-transferase, glutathione peroxidase) activities and glutathione level in the brain, ovary, and uterus of rats (p<0.05). Lastly, hesperidin preserved the histological structure of the ovary and uterus of rats exposed to VCD. Conclusions Overall, the rescue role of hesperidin on VCD-induced toxicity in the brain and reproductive organs of female rats may be due to its antioxidative and anti-inflammatory properties.

Background The aim of this study was to investigate the effects of selenium, zinc, insulin, and metallothionein on oxidative damage and metallothionein (MT) gene expression levels in streptozotocin (STZ)-induced type 1 diabetic rats exposed to Cd. Methods Rats were categorized under eight groups (control, STZ, Cd, STZ + Cd, Group 5, Group 6, Group 7, and STZ + Cd + MT [n:8/group]) were used. After diabetes was induced by STZ (55 mg/kg, i.p.), Cd was administered (1 mg/kg CdCl, orally) for 4 weeks. In cadmium-treated groups selenium (Na2SeO3 1.5 mg/kg, i.p.), zinc (ZnSO4 10 mg/kg via oral gavage), insulin (insulin glargine, 2U/day, s.c.), and MT (1mg/kg, every other 10 days, s.c.) were administered. MT gene expression levels, MDA levels, GPx, SOD, and CAT activity levels were determined in liver and kidney tissues. Results MT gene expression and MDA levels increased (p < 0.05) while GPx and SOD activity levels decreased (p < 0.05) in STZ, Cd, and STZ + Cd groups. In Group 5, Group 6, Group 7, and Group 8 groups MT gene expression and MDA levels were decreased while GPx and SOD activity levels were increased (p < 0.05). CAT activity significantly increased (p < 0.05) in STZ + Cd group while there were no significance in other groups (p > 0.05). Compared to the control, Group 5, Group 6, Group 7, and Group 8 groups provided no difference for alanine aminotransferase, aspartate aminotransferase, blood urea nitrogen and creatinine levels (p > 0.05). Conclusions Our results suggest that Se, insulin, Zn and MT may have protective effects against hepatotoxicity and nephrotoxicity caused by Cd exposure in diabetic rats by reducing oxidative stress and MT gene expression levels.

Background Diabetes mellitus is a chronic metabolic disorder that undesirably affects both central and peripheral nervous systems through the apoptosis of neurons. Insulin and insulin-like growth factors (IGFs) inhibit apoptosis of oligodendrocytes. The objective of this study was to determine whether oral insulin in the form of nanoparticles may have similar effects to injectable insulin in increasing the gene expression of IGF1 and IGF2 . Methods Insulin-loaded trimethyl chitosan nanoparticles were prepared using the polyelectrolyte complex method and characterized for size, polydispersity index, zeta potential, drug loading, and entrapment efficiency. An in vivo study was performed in different groups of male Wistar rats with diabetes mellitus type 1 treated with insulin-loaded trimethyl chitosan nanoparticles and subcutaneous injection of trade insulin (neutral protamine Hagedorn). The hippocampus of rats were studied for the expression of IGF1 and IGF2 genes by using real-time PCR, and the fold changes in gene expression were evaluated using the 2 −ΔΔCt method. Results The expression of IGF1 and IGF2 genes in the groups treated with nano-insulin and injected insulin were significantly higher than that in the diabetic control group (p<0.001) and meaningfully lower than that in the healthy control group. However, there was no significant difference to the treated groups. Conclusion Our findings suggest that future research might provide a new formulation of drugs for treating type 1 diabetes, in the form of oral insulin.

Background Mammals, particularly large domestic ones, are considered to be year-round homeotherms. Surprisingly, however, very few long-term studies of the stability of core temperature of large domestic mammals have been conducted. Methods We monitored the auricular temperature and rectal temperature of goats, sheep, cows, and donkeys monthly for 2 years and compared their annual variation with their daily and day-to-day variations. Results Although ambient temperature varied from 8 °C in the winter to 30 °C in the summer, auricular temperature varied less than 0.5 °C, and rectal temperature varied less than 0.3 °C. We found that the daily oscillation in body temperature was up to three times as large as the day-to-day and month-to-month variations and that month-to-month variation was negligibly larger than day-to-day variation. Conclusion Our results confirm persistent homeothermy in large domestic mammals with unrestricted access to food and water and provide a quantitative measure of the relationship between long-term homeothermy and the wider range of daily/circadian oscillation.

Background In this study, Grewia optiva Drummond ex Burret root extracts were assessed for use as a remedy for oxidative stress, diabetes mellitus and neurological disorders. Methods The antioxidative potentials of the extracts were determined using DPPH and ABTS assays, whereas their enzyme inhibitory potentials were determined against acetylcholinesterase (AChE), butyrylcholinesterase (BChE), α-glucosidase and α-amylase. In the in vivo experiments, methanol extract was orally administered to mice (n = 5) at four doses of 200, 300, 400 and 500 mg kg –1 for 30 days and its effect on glucose, triglycerides, total cholesterol, etc. were investigated. Results The highest free radical scavenging activities against DPPH and ABTS radicals were recorded for the methanol and ethyl acetate extracts, and their respective IC 50 values were 75 and 88 μg/mL. In addition, these two fractions were highly active in inhibiting AChE and BChE, with IC 50 values of 120 and 185 μg/mL, respectively. Moderate inhibition (μg/mL) was recorded against α-glucosidase (69.02 ± 1.02 and 64.29 ± 2.41) and α-amylase (65.12 ± 2.02 and 63.29 ± 1.41) and these were comparable to the inhibitory activities exhibited by the standard, acarbose. All the extracts showed high phenolic and flavonoid contents, which correlated with their antioxidant, anticholinesterase, α-glucosidase and α-amylase activities. The phenolic compounds in the crude extract and fractions were determined using the standard HPLC method and bioactive compounds, namely, morin, ellagic acid, kaempferol-3-(p-coumaroyl-diglucoside)-7-glucoside, apigenin-7-O-rutinoside, quercetin-3-(caffeoyl-diglucoside)-7-glucoside, etc., which were detected at various retention times. Significant decrease in cholesterol, triglyceride and blood glucose levels were observed. Conclusion G. optiva is a good source of antioxidants and other phytochemicals, some of which possess anticholinesterase, anti-glucosidase, and anti-amylase activities, and can be used to treat different health conditions such as oxidative stress, neurological disorders, and diabetes mellitus.

Background The in vivo anticancer effect of the Trema orientalis leaves crude methanol extract (TLME) was screened against Ehrlich ascites carcinoma (EAC) in Swiss albino mice. Materials and methods The cytotoxic activity of TLME was determined in vitro by the 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay. The growth inhibitory activity and morphological alterations were determined by the hemocytometer counting of the EAC cells using trypan blue dye. The apoptotic cells were assessed by DAPI (4′,6-diamidino-2-phenylindole) staining. The hematological and biochemical parameters of experimental mice were also estimated. Results After treatment with the TLME, the viable tumor cell count, morphological changes and nuclear damages of the EAC cells were observed along with the hematological parameters of the experimental mice. The LD 50 of TLME was 3120.650 mg/kg body weight, and this extract was proven to be safe at a dose of as high as 800 mg/kg body weight. The oral administration of the TLME at 400 mg/kg body weight resulted in approximately 59% tumor cell growth inhibition compared with the control mice, with considerable apoptotic features, including membrane blebbing, chromatin condensation, nuclear fragmentation and aggregation of the apoptotic bodies in DAPI staining under a fluorescence microscope. The TLME also dose-dependently restored the altered hematological parameters to approximately normal levels. The TLME exhibited bolstering cytotoxic effect against the EAC cell with the IC 50 value of 29.952 ± 1.816 μg/mL. Conclusion The TLME has potential as a natural anti-cancer product with apoptosis induction property and cytotoxicity against carcinoma cells.

Background The present study was conducted to examine the antidiabetic effects of Scrophularia striata ethanolic extract and to evaluate its effects on oxidative stress markers and RAGE and S100A8 gene expressions in the kidney of type 1 diabetic rats. Methods A total of 36 rats (weight 200–250 g) were randomly assigned into six groups as follows: Cnt, Cnt + S. striata 100, and Cnt + S. striata 200 that received normal saline, 100 mg/kg bw, and 200 mg/kg bw of ethanol extract of S. striata , respectively; and group Dibt, Dibt + S. striata 100, and Dibt + S. striata 200 that received normal saline, 100 mg/kg bw, and 200 mg/kg bw of ethanol extract of S. striata , respectively. Type 1 diabetes was induced in rats by a single injection of streptozotocin (55 mg/kg bw). After 60 days of treatment, biochemical factors and oxidative stress markers (superoxide dismutase [SOD] and malondialdehyde [MDA]) were measured using spectrophotometric methods. RAGE and S100A8 gene expressions were analyzed using real-time polymerase chain reaction. Results Diabetes significantly impairs serum and urine fasting blood glucose (FBG), lipid profile, creatinine, urea, and albumin parameters. After the treatment with S. striata extract, these parameters are close to the normal range. It was shown that the S. striata extract significantly decreased the kidney expression levels of RAGE and S100A8 genes and improved oxidative stress markers (SOD and MDA) in the kidney tissues when compared with the diabetic control group. It was also found that the beneficial effects of the S. striata were dose dependent. Conclusions The ethanolic extract of S. striata has beneficial antidiabetic effects. Moreover, by reducing RAGE and S100A8 gene expressions and by improving oxidative stress, S. striata might be used as adjuvant treatment for diabetic complications.

Background In traditional medicine, Allium cepa Linnaeus is used for the treatment of several disease conditions. Whilst reports abound on the effects of several cultivars of A. cepa L on biochemical parameters, similar information on the red cultivar is scarce. This study examines the effects of the methanol extract of the red cultivar A. cepa L on some serum biochemical parameters in experimental Wistar rats. Materials and methods Fifty-five Wistar rats were divided into three groups (A, B and C), which include 25, 25 and 5 rats, respectively. The rats in Groups A and B were sub-divided into 5 groups of 5 rats. Each rat was administered a certain dose of methanol extract of the red cultivar A. cepa L for 14 days (Group A) or 28 days (Group B). Group C rats served as the control and were administered with distilled water (10 mL/kg). Results A. cepa L administration resulted in dyslipidaemia, hyponatremia, hypokalaemia and hyperchloraemia; a significant (p < 0.05) decrease in hepatic enzymes and a significant (p < 0.05) increase in serum bicarbonate, bilirubin and its fractions. Conclusions These biochemical results indicate that the excessive and prolonged medicinal consumption of A. cepa L products beyond 7 days may induce moderate hepatic injury and mild renal dysfunction and may complicate disease conditions, such as hypertension and diabetes. Thus, in order to minimize its toxic effects, it is recommended that A. cepa L products should not be used for more than seven consecutive days or beyond a dosage of 90 mg/kg.