RNA interference as a plausible anticancer therapeutic tool

RNA interference has created a breakthrough in gene silencing technology and there is now much debate on the successful usage of RNAi based methods in treating a number of debilitating diseases. Cancer is often regarded as a result of mutations in genomic DNA resulting in faulty gene expression. The occurrence of cancer can also be influenced by epigenetic irregularities in the chromatin structure which leads to alterations and mutations in DNA resulting in cancer cell formation. A number of therapeutic approaches have been put forth to treat cancer. Anti cancer therapy often involves chemotherapy targeting all the cells in common, whereby both cancer cells as well as normal cells get affected. Hence RNAi technology has potential to be a better therapeutic agent as it is possible to deactivate molecular targets like specific mutant genes. This review highlights the successful use of RNAi inducers against different types of cancer, thereby paving the way for specific therapeutic medicines.     

Propylthiouracil attenuates acetaminophen-induced renal damage in the rat

BACKGROUND: To date, there is no specific antidote to acetaminophen poisoning. Propylthiouracil (PTU) has been shown to be protective against acetaminophen (APAP)-induced liver damage in rats; however, the nephroprotective effect of propylthiouracil has not been studied yet. METHODS: In order to verify this, rats were given different doses of PTU (100, 200 or 400 mg/kg per body weight, orally) 1 h before a nephrotoxic dose of APAP (1,000 mg/kg per body weight, intraperitoneally (i.p.)). RESULTS: Propylthiouracil pretreatment significantly reduced APAP-induced nephrotoxicity in a dose-dependant manner, as evidenced by reduction in plasma creatinine and by amelioration of renal pathology (interstitial congestion, tubular cell degeneration and necrosis). CONCLUSION: The mechanism of protection by PTU is probably not due to the sparing effect of non-protein thiol (approximately 95% of which is reduced glutathione), as similar depletion of renal glutathione was observed regardless of PTU pretreatment; other mechanisms are suggested.     

Chemopreventive effect of Cynodon dactylon (L.) Pers. extract against DMH-induced colon carcinogenesis in experimental animals

The present study was aimed at evaluating the chemopreventive property of Cynodon dactylon. The antioxidant, antiproliferative and apoptotic potentials of the plant were investigated by 1,1-diphenyl-2-picrylhydrazyl (DPPH) assay, nitric oxide radical scavenging activity (NO^?) and MTT assay on four cancer cell lines (COLO 320 DM, MCH-7, AGS, A549) and a normal cell line (VERO). In vivo chemopreventive property of the plant extract was studied in DMH-induced colon carcinogenesis. The methanolic extract of C. dactylon was found to be antiproliferative and antioxidative at lower concentrations and induced apoptotic cell death in COLO 320 DM cells. Treatment with methanolic extract of C. dactylon increased the levels of antioxidant enzymes and reduced the number of dysplastic crypts in DMH-induced colon of albino rats. The present investigation revealed the anticancer potential of methanolic extract of C. dactylon in COLO 320 DM cells and experimentally induced colon carcinogenesis in rats.     

In vitro antioxidant evaluation and total phenolics of methanolic leaf extracts of Nyctanthes arbor-tristis L.

AIM： To investigate the in vitro antioxidant activity and total phenolic content of the methanolic leaf extract of Nyctanthes arbor-tristis L. （NA）. METHODS： The sample was tested using five in vitro antioxidant methods （1, 1-diphenyl-2-picryl hydrazine radical scavenging activity （DPPH）, hydroxyl radical-scavenging activity （-OH）, nitric oxide scavenging activity （NO）, superoxide radical-scavenging activity, and total antioxidant activity） to evaluate the in vitro antioxidant potential of NA and the total phenolic content （Folin-Ciocalteu method）. The extract showed good free radical scavenging property which was calculated as an IC50 value. RESULTS： IC50 （Half maximal inhibitory concentration） of the methanolic extract was found to be 57.93 μg.mL-1 for DPPH, 98.61 μg.mL-1 for-OH, 91.74 μg.mL-1 for NO, and 196.07 μg.mL-1 for superoxide radical scavenging activity. Total antioxidant ca- pacity of the extract was found to be （1198± 24.05） mg ascorbic acid for the methanolic extract. Free radical scavenging activity ob- served in the extracts of NA showed a concentration-dependent reaction. The in vitro scavenging tested for free radicals was reported to be due to high phenolic content in the leaf extract. The leaf extract of NA showed the highest total phenolic content with a value of 78.48 ± 4.2 equivalent nag TAE/g （tannic acid equivalent）. CONCLUSIONS： N. arbor-tristis leaf extract exhibited potent free radical scavenging activity. The finding suggests that N. arbor-tristis leaves could be a potential source of natural antioxidant.     

In vitro antioxidant,antidiabetic and antilipidemic activities of Symplocos cochinchinensis (Lour.) S. Moore bark

Symplocos cochinchinesis is used in Indian system of traditional medicine to treat diabetes mellitus. The present study investigates the in vitro antioxidant, antidiabetic and antilipidemic activities of S. cochinchinensis bark methanolic extract (SCBe) in streptozotocin (STZ) induced diabetic rats. In in vitro studies SCBe showed very good scavenging activity on 2,2-diphenyl-picrylhydrazyl (DPPH) (IC₅₀ 820.34 ± 1.74 μg/ml), hydroxyl (IC₅₀ 884.19 ± 0.45 μg/ml) and nitric oxide (IC₅₀ 860.21 ± 1.18 μg/ml) radicals, as well as high reducing power. SCBe (250 and 500 mg/kg) was administered to STZ (40 mg/kg) induced diabetic rats for 28 days. SCBe showed a significant decrease in blood glucose and significant increase in plasma insulin and liver glycogen levels in treated diabetic rats. Further, SCBe showed antilipidemic activity as evidenced by significant decrease in serum TC, TG, LDL-C levels and significant increase in HDL-C level in treated diabetic rats. SCBe also restored the altered plasma enzymes (SGOT, SGPT and ALP), total protein, urea and creatinine levels to near normal. The action of SCBe was comparable to the antidiabetic drug glibenclamide. Results of this experimental study indicated that SCBe possessed antioxidant, antidiabetic and antilipidemic activities.     

The effects of music on clients with learning disabilities: a literature review

The aim of this paper was to promote the use of musical interventions with clients with learning disabilities. Musical interventions with this group of clients were found to be effective in reducing self-injurious behaviour, aggression and other behaviour, which challenge the service providers. Music was also found to have the potential to improve the communication skills of clients and to maintain their psychological well being. A review of the literature shows that music, though not widely used in the field of learning disabilities, can be an effective medium through which the quality of life of clients can be enhanced.     

Arg389Gly-beta1-adrenergic receptors determine improvement in left ventricular systolic function in nonischemic cardiomyopathy patients with heart failure after chronic treatment with carvedilol

OBJECTIVE: Administration of the beta-adrenergic receptor blocker carvedilol to patients with chronic heart failure leads to clinically significant benefits, including improvement in left ventricular systolic function in some, but not all, patients. We sought to determine the basis of the variable effect obtained with carvedilol in patients with heart failure. Carvedilol blocks both beta1-adrenergic and beta2-adrenergic receptors, and both receptors exist as polymorphisms. We aimed to determine whether these polymorphisms contribute to variability in response to carvedilol in patients with chronic heart failure. METHODS: We retrospectively and prospectively investigated 135 patients with nonischemic cardiomyopathy and chronic stable heart failure (New York Heart Association class II, III) treated with carvedilol. Baseline echocardiography was obtained before introduction of carvedilol and repeated after stabilization of a maximally tolerated dose of carvedilol (50-100 mg/day) for at least 1 year. Polymerase chain reaction and restriction fragment length polymorphism analysis were used to genotype beta1-adrenergic and beta2-adrenergic receptor polymorphisms. RESULTS: When grouped according to receptor polymorphisms patients were well matched for severity of heart failure, comorbidity and treatment. No significant difference was observed in baseline left ventricular ejection fraction (LVEF) between groups (P>0.05). After 1.5 years of treatment with carvedilol patients with Arg389Arg-beta1-adrenergic receptors had a significantly greater improvement in LVEF compared with Gly389 carriers (Arg389Arg 18.8%; Arg389Gly 9.4%; Gly389Gly 6.0%; P<0.001) whereas there were no differences attributable to other beta1-adrenergic and beta2-adrenergic receptor polymorphisms (P>0.05). CONCLUSION: In patients with nonischemic dilated cardiomyopathy, carvedilol leads to a significantly greater improvement in LVEF in patients with the Arg389Arg-beta1 adrenergic receptor phenotype.     

Lymphoscintigraphy as a diagnostic tool in patients with lymphedema of filarial origin--an Indian study

Lymphedema is a common clinical problem. Filariasis is the commonest cause of lymphedema in India and is a chronic debilitating disease. The purpose of this study is to highlight the role of lymphoscintigraphy in the evaluation of lymphedema. Our study population consisted of 418 patients diagnosed with filarial lymphedema of different clinical stages referred for lymphoscintigraphy of the limbs by the lymphologist at our institution. An analysis of the various studies was done to determine how lymphoscintigraphy can be useful in documentation of the diagnosis, evaluation, as a screening procedure to prevent progression, and to enhance management of filarial lymphedema.     

Effect of cyclophosphamide treatment on selected lysosomal enzymes in the kidney of rats.

The anti-cancer drug cyclophosphamide (CYP) is nephrotoxic besides being urotoxic thereby limiting its clinical utility. Since the nephrotoxicity of CYP is less common compared to its urotoxicity, not much importance has been given for the study of mechanism of CYP-induced nephrotoxicity. The aim of the present study is to investigate the possible role of lysosomal enzymes in CYP-induced renal damage. Adult female Wistar rats weighing 200-250 g were used for the study. The rats were administered single-intraperitoneal injection of CYP at the dose of 150 mg/kg body wt and sacrificed at various time intervals 6, 16 or 24 h after the dose of CYP. The control rats were administered saline alone. Nephrotoxicity was assessed by measuring plasma creatinine and urea and histopathology of the kidney. The kidney was weighed and used for the assay of lysosomal enzymes namely acid phosphatase, beta-glucuronidase and N-acetylglucosaminidase and total protein content. Histologically, the CYP-treated rat kidneys showed progressive renal damage with increase in time after treatment. Glomerular nephritis, cortical tubular vacuolization and interstitial edema were observed in the CYP-treated rats. Surprisingly, a significant drastic decrease (instead of an increase) in the activities of lysosomal enzymes was observed in the kidneys of CYP-treated rats at 16 and 24 h as compared with the control. A highly significant increase (270%) in protein content was observed in the kidneys of the CYP-treated rats as compared with the control. Decrease in the activities of lysosomal protein digestive enzymes may contribute to CYP-induced renal damage. The accumulation of abnormal amounts of the protein in the kidney may be due at least in part to defect in lysosomal enzyme activity and contribute to renal damage.     

β-sitosterol prevents lipid peroxidation and improves antioxidant status and histoarchitecture in rats with 1,2-dimethylhydrazine-induced colon cancer

Oxidative stress has become widely viewed as an underlying condition in diseases such as ischemia/reperfusion disorders, central nervous system disorders, cardiovascular disease, cancer, diabetes, etc. The role that antioxidants play in the process of carcinogenesis has recently gained considerable attention. β-Sitosterol, a naturally occurring sterol molecule, is a relatively mild to moderate antioxidant and exerts beneficial effects in vitro by decreasing the level of reactive oxygen species. The present study evaluated the antioxidant potential of β-sitosterol in 1,2-dimethylhydrazine (DMH)-induced colon carcinogenesis. The enzymatic and nonenzymatic antioxidants and lipid peroxides in colonic and hepatic tissues were evaluated. Generation of reactive oxygen species, beyond the body's endogenous antioxidant capacity, causes a severe imbalance of cellular antioxidant defense mechanisms. Elevated levels of liver lipid peroxides by DMH induction were effectively decreased by β-sitosterol supplementation. β-Sitosterol also exhibited a protective action against DMH-induced depletion of antioxidants such as catalase, superoxide dismutase, glutathione peroxidase, glutathione reductase, glutathione S-transferase, and reduced glutathione in colonic and hepatic tissues of experimental animals. Supplementation with β-sitosterol restored the levels of nonenzymatic antioxidants (vitamin C, vitamin E, and glutathione). Histopathological alterations in DMH-induced animals were restored to near normal in rats treated with β-sitosterol. Thus, β-sitosterol by virtue of its antioxidant potential may be used as an effective agent to reduce DMH-induced oxidative stress in Wistar rats and may be an effective chemopreventive drug for colon carcinogenesis.