Nanopolyphenols: Perspective on oxidative stress-induced diseases

Recently nanopolyphenols are gaining widespread interest in the drug discovery domain. Nanonization of polyphenols has greatly affected the therapeutic index owing to improvement in pharmacokinetic and biopharmaceutical obstacles linked with the use of natural polyphenols. They have been looking at an emerging paradigm for an array of disease symptoms. In this article, we have explored the therapeutic potential of nanopolyphenols in oxidative stress-induced diseases such as neurodegeneration, cancer, obesity, and diabetes. This article will present the current state of the art of various nanopolyphenols targeting oxidative stress-induced diseases. The advanced fabrication strategies presented for polyphenols including nanocrystal, mesoporous silica nanoparticles, nanoparticles, nanoliposome, gold nanoparticle, and nanosuspension are discussed. The information presented in light of recent in vitro, in vivo, and clinical evidence for nanoformulation and delivery of polyphenols may show a new dimension to future research in the realm of herbal therapy for oxidative stress- induced diseases. Significant information on the molecular mechanisms underlying linkages of oxidative stress with neurodegenerative diseases, cancer, obesity, and diabetes is discussed. Valuable information on dietary polyphenols in these diseases and their clinical data is presented. Based on different experimental evidence, the review findings support phenomenal therapeutic strategies for nanopolyphenolic fabrication with extended benefits and a condensed time frame. The status of clinical trials conducted on nanopolyphenols is presented. Although clinical trials conducted on nanopolyphenols for mentioned diseases are few, we have tried to present as much available clinical data in this article.

A Simple Biogenic Method for the Synthesis of Silver Nanoparticles using Syngonium podophyllum, an Ornamental Plant.

The potential of ornamental plant Syngonium podophyllum leaf extract has been explored for the synthesis of silver nanoparticles, which was confirmed by appearance of absorption peak at 420 nm in ultraviolet-visible (UV-Vis) spectrum. Silver nanoparticles were predominantly spherical in shape and size observed under scanning electron microscopy (SEM) was in the range of 11 to 26 nm. A sharp signal recorded at 3 keV under energy-dispersive X-ray (EDX) spectrum indicated the presence of elemental silver nanoparticles. Zeta potential was measured as -26.77 mV, which indicated the presence of moderately stable silver nanoparticles in the solution. Under Fourier transform infrared (FTIR), two prominent bands were assigned, i.e., 3,454.89 cm-1 represents the O-H stretching vibration and 1,637.46 cm-1 represents the -NH stretching vibration of the amide group. It indicates that protein might be responsible for the synthesis.

Enhancement of Gentamicin Sensitivity in Enterococcus faecalis using Antidiabetic Molecule Gliclazide.

Enterococci, a low-grade pathogen, emerged as a potent nosocomial agent and have recently drawn the global attention because of resistance issues. To deal with this serious threat and reversal of drug sensitivity pattern, we made an attempt to sensitize the cells of Enterococcus faecalis with an oral hypoglycemic molecule gliclazide belonging to the class sulfonylurea. Interestingly, it was observed that results were quite encouraging as it was able to enhance gentamicin sensitivity by reducing the minimum inhibitory concentration (MIC). The decrease in MIC of gentamicin to E. faecalis is an indicator of reversibility of drug resistance. The findings have confirmed the concept that prior course or combination therapy of oral hypoglycemic drug with antibiotic gentamicin can be effective against Enterococci strains. However, auxiliary tests still need to be carried out further to understand the exact mechanism of the enhancement procured by gliclazide. The results have sowed the seeds of the concept of using gliclazide as a drug-resistant reversal molecule.

Pancreatic Lipase Inhibitor from Food Plant: Potential Molecule for Development of Safe Anti-obesity Drug.

Obesity is a global health concern, widely recognized as the largest and fastest growing public health problem in the developed and developing countries associated with high morbidity and mortality. It is a multifactorial disease resulting in significant impairment of health. The strategies used for the treatment of obesity generally comprise of prescription of drugs and surgery. Number of basic mechanisms has been considered for obesity management but these entail serious complexities. In recent year’s pancreatic lipase, a principal lipolytic enzyme secreted by the pancreas has gained importance as -obesity target. As the PL acts in the duodenum it has least involvement with the blood or brain, avoiding a lot of drug related side effects. Although PL has been considered as good target for obesity management, the drug discovery and development in this section is not abundantly explored. Numerous natural molecules have been established for pancreatic lipase inhibitory activity but only orlistat (tetrahydrolipstatin), a saturated derivative of lipstatin designed to inhibit the action of gastrointestinal lipase approved by Food and Drug Administration (FDA) for longterm usage. However, it has severe side effects. Therefore, the possible treatment of obesity using natural products is an extensive field to be explored. Several plant derived molecules including medicinal plants have been reported for their pancreatic lipase inhibitory activity. In particular pancreatic lipase inhibitor from food plants can be considered as a good source for the discovery of a safe anti-obesity agent due to possible active principle as edible component. Present review mainly focuses on the pancreatic lipase inhibitor from food plants and its potential in the development of safe anti-obesity drug.

Predictive Perspectives of Disease-Transformed Protein Biomarkers.

With advancement in instrumentation, computation and understanding of disease etiology, proteomics has been expanded to harness the knowledge of change in protein folding and misfolding, protein-protein interaction, protein modification, etc. during progression of disease which is a source of discovery for various biomarkers including predictive biomarkers. Various methodologies for disease prediction are reported using ‘omics’ technology; however, advancement in proteomics with discovery of protein biomarker allows for the estimation of disease risk from years to decades before any disease even manifests internally. Specific proteins as disease biomarkers that appear in the body fluid/diseased tissues are generally measured. Recently, new proteomics technologies are also being developed in order to facilitate both the highthroughput and high-sensitivity requirements of diseaserelated applications of proteomics and possibly providing the framework for prediction of diseases. Therefore, there is a growing interest in proteomics technologies to discover processes that are involved in various diseases, to discover new biomarkers that correlates with the prediction and early detection of diseases. Now there is change in research thinking where already known biomarkers alone or in combination of others are under investigation for advanced application like in prediction and early detection of chronic diseases. In this review, we have emphasized the prediction perspective of some of the protein biomarkers like CA-125, Lp-PLA2 and tau protein for diseases like cancers, cardiovascular diseases, and Alzheimer’s respectively.

Biological Synthesis of Antimicrobial Silver Nanoparticles by Phaseolus vulgaris Seed Extract.

Biological synthesis of silver nanoparticles is generally a time-consuming process in comparison to chemical process. Despite voluminous reports on biological synthesis of silver nanoparticles, there is still a challenge to develop fast synthesis of nanoparticles in the range of minutes/seconds through biological route. Several disadvantages are generally being posed by slow biological synthesis of silver nanoparticles including cost of operation. To overcome this difficulty, fast and simple method has been developed for the synthesis of silver nanoparticles, using Phaseolus vulgaris seed extract simply by increasing the temperature. The method is very quick and the color change of the reaction can be observed within 20 seconds. This process was able to synthesize silver nanoparticles within 80 seconds at 100oC which was confirmed by absorption peak at 413.79 nm in UV-visible spectrum. Initially, it was observed that P. vulgaris seed extract was unable to synthesize silver nanoparticles at 37oC even after 24 hours. The silver nanoparticles generated by this method were predominantly spherical in shape and in the range of approximately 4 to 30 nm in size, as characterized by transmission electron microscopy (TEM). On FTIR analysis, it was found that the nanoparticles possessed definite surface exposed groups. Generated silver nanoparticles showed antimicrobial activity against clinical isolates, Escherichia coli and Candida albicans. Thus, this biological process offers a simple, ecofriendly and very fast synthesis of antimicrobial silver nanoparticles.

Surgical Treatment of Obesity and Diabetes.

Surgery for obesity is the last option but it is the most effective. Resolution of comorbid diseases with obesity occurs depending upon the amount of weight loss, age of the patients, duration of comorbid disorders. After malabsorptive surgeries, patient has to be on life-long vitamin supplements. Various types of surgeries done in morbid obesity with their merits and demerits have been described in this review.

Simultaneous occurrence of toxic epidermal necrolysis and neuroleptic malignant syndrome.

Toxic epidermal necrolysis (TEN) is an acute life-threatening blistering disease characterized by involvement of the skin, multiple mucous membranes and internal organs. It is most commonly precipitated by the administration of medications like anticonvulsants. Neuroleptic malignant syndrome (NMS) is a rare complication of neuroleptic therapy characterized by catatonic behavior, generalized muscular rigidity, hyperthermia and autonomic dysfunction. An 18-year-old girl presenting with simultaneous appearance of TEN and NMS following anti-psychotic drugs given for bipolar mood disorder, is reported for the rare association and her complete recovery.

Mitral valve replacement on a beating heart.

We report the case of a patient who needed mitral valve replacement but was at a high risk of myocardial injury with the conventional technique (cardioplegic arrest on cardiopulmonary bypass). Valve replacement was carried out on a beating heart on cardiopulmonary bypass by perfusing the heart continuously with oxygenated noncardioplegic normothermic blood via the coronary sinus.

Retrograde coronary sinus perfusion for management of coexistent critical unstable carotid and coronary artery disease.

The case report describes a difficult and not uncommon situation of a patient suffering from an evolving myocardial infarction with hemodynamic instability along with a critical bilateral extracranial carotid artery stenosis. A technique of retrograde coronary sinus perfusion was used to temporarily stabilize the cardiac status while the carotid lesion was being tackled.

Gallbladder disorders and type 2 diabetes mellitus--a clinic-based study.

AIMS OF THE STUDY: To study the prevalence of gallbladder disorders in type 2 diabetic patients and their correlation with patient factors like age, sex, weight, duration of diabetes and autonomic neuropathy. METHODOLOGY: Fifty type 2 diabetic patients and 30 healthy controls underwent realtime ultrasonography to study the prevalence of gallbladder disorders. The fasting gallbladder volume and contraction 60 minutes after a fatty meal of the diabetic subjects were compared with 30 age and sex matched healthy volunteers. The age, sex, weight, duration of diabetes, autonomic neuropathy, control of diabetes were correlated to the prevalence of gallbladder disorders in diabetic patients. RESULTS: 32% of the diabetic patients had ultrasonographic evidence of gallstones, as compared to 6.7% in healthy subjects. 73.7% of the diabetic patients with gallbladder disorders were females. Mean fasting gallbladder volume was significantly increased in diabetic patients (26.2 cm3) as compared to non-diabetic healthy subjects (15.8 cm3). Further mean fasting gallbladder volume of diabetic patients with gallbladder disorder (28.1 cm3) was found to be significantly larger than that of those patients without gallbladder disorder (24.6 cm3). Mean percentage of contractions of gallbladder 60 min after fatty meal was reduced in diabetic patients (53.1%) and it was observed to be further reduced in the patients with gallbladder disorder (41.8%). Mean fasting gallbladder volume was larger in diabetic subjects with autonomic neuropathy, than those without. However, difference in mean percentage contraction of gallbladder 60 min after fatty meal was not statistically significant. Mean duration of diabetes was significantly longer in diabetic patients with gallbladder disorder. CONCLUSIONS: We conclude that type 2 diabetic patients have increased prevalence of gallbladder disorder which can only partially be explained by autonomic neuropathy leading, to increased fasting volume. Factors like decreased cholecystokinin or decreased sensitivity of the smooth muscle of gallbladder to normal level of cholecystokinin need to be studied.

Nature of lesion in cerebrovascular stroke patients: clinical stroke score and computed tomography scan brain correlation.

AIM: To differentiate between cerebral infarct and intracerebral haemorrhage on the basis of clinical stroke score (Siriraj Stroke Score and Guy's Hospital Score) and to find out the sensitivity and overall accuracy of these scoring systems by comparing it with CT scan findings. MATERIAL AND METHODS: Two hundred patients with acute stroke were analysed by Siriraj and Guy's Hospital Score simultaneously CT scan was performed and patients with subarachnoid haemorrhage, tuberculoma, tumours and trauma were excluded. RESULT: CT scan revealed cerebral infarction in 152 (76%) patients and cerebral haemorrhage in 48 (24%) patients. The sensitivity of Siriraj Stroke Score was 92.54% for infarction and 87% for haemorrhage (equivocal and infratentorial cases were excluded) and it's overall accuracy was 91.11%. The Guy's Hospital Score had a sensitivity of 93.42% for infarction, 66.66% for haemorrhage and overall accuracy was 87%. CONCLUSION: Siriraj Stroke Score is easier to use at bed side and has a greater accuracy (especially in diagnosis of haemorrhage) than the Guy's Hospital Score.

Efficacy of Terminalia arjuna in chronic stable angina: a double-blind, placebo-controlled, crossover study comparing Terminalia arjuna with isosorbide mononitrate.

BACKGROUND: Terminalia arjuna, an Indian medicinal plant, has been reported to have beneficial effects in patients with ischemic heart disease in a number of small, open studies. The need for a double-blind, randomized, placebo-controlled study with adequate sample size has long been felt. The bark extract (IPC-53) contains acids (arjunic acid, terminic acid), glycosides (arjunetin arjunosides I-IV), strong antioxidants (flavones, tannins, oligomeric proanthocyanidins), minerals. etc. and exhibits antifailure and anti-ischemic properties. METHODS AND RESULTS: Fifty-eight males with chronic stable angina (NYHA class II-III) with evidence of provocable ischemia on treadmill exercise test received Terminalia arjuna (500 mg 8 hourly), isosorbide mononitrate (40 mg/daily) or a matching placebo for one week each, separated by a wash-out period of at least three days in a randomized, double-blind, crossover design. They underwent clinical, biochemical and treadmill exercise evaluation at the end of each therapy which were compared during the three therapy periods. Terminalia arjuna therapy was associated with significant decrease in the frequency of angina and need for isosorbide dinitrate (5.69+/-6.91 mg/week v. 18.22+/-9.29 mg/week during placebo therapy, p<0.005). The treadmill exercise test parameters improved significantly during therapy with Terminalia arjuna compared to those with placebo. The total duration of exercise increased (6.14+/-2.51 min v. 4.76+/-2.38 min, p<0.005), maximal ST depression during the longest equivalent stages of submaximal exercise decreased (1.41+/-0.55 mm v. 2.21+/-0.56 mm, p<0.005), time to recovery decreased (6.49+/-2.37 min v. 9.27+/-3.39 min, p<0.005) and higher double products were achieved (25.75+/-4.81x10(3) v. 23.11+/-4.83x10(3), p<0.005) during Terminalia arjuna therapy. Similar improvements in clinical and treadmill exercise test parameters were observed with isosorbide mononitrate compared to placebo therapy. No significant differences were observed in clinical or treadmill exercise test parameters when Terminalia arjuna and isosorbide mononitrate therapies were compared. No significant untoward effects were reported during Terminalia arjuna therapy. CONCLUSIONS: Terminalia arjuna bark extract, 500 mg 8 hourly, given to patients with stable angina with provocable ischemia on treadmill exercise, led to improvement in clinical and treadmill exercise parameters as compared to placebo therapy. These benefits were similar to those observed with isosorbide mononitrate (40 mg/day) therapy and the extract was well tolerated. Limitations of this study include applicability of the results to only men with chronic stable angina but not necessarily to women, as they were not studied.

Ankle brachial index as a predictor of generalized atherosclerosis.

OBJECTIVE: To assess ankle brachial index (ABI) as a screening method to target subclinical atherosclerosis in middle aged individuals. MATERIAL AND METHODS: Total 160 patients over the age of 40 years were included in the study for a period of 16 months. Their ABI was determined either by colour Doppler method (30 patients) and/or sphygmomanometry (all 160 patients). A value of < 0.9 was taken as cutoff point for significant stenosis. RESULTS: Total 69 patients out of total of 160 had significantly low ABI value (43.12%) which shows that there is a very high incidence of low ABI in the community. Overall > 50% of the patients were largely asymptomatic and had presence of two or more risk factors. ABI < 0.9 was a good screening test to detect such individuals at an earlier stage (sub-clinical). CONCLUSION: A significantly low (< 0.9) ABI value can detect subclinical atherosclerotic vascular involvement and predict future occurrence of preventable major vascular event.