Quality Control Standards for the Roots of Three Plumbago Species

Physicochemical parameters of roots of three Plumbago species, Plumbago capensis, P. rosea and P. zeylanica belonging to Plumbaginaceae were analyzed. Microbial contamination, aflatoxins, pesticide residue and heavy metal content were also determined. Attempt has also been made to estimate the biologically active chemical plumbagin present in them and the data compared. The study ensures that the quality control parameters do help in the proper standardization of the crude drugs in drug development process for global acceptance.     

Chemopreventive efficacy of inositol hexaphosphate against prostate tumor growth and progression in TRAMP mice.

PURPOSE: Herein, for the first time, we evaluated the in vivo chemopreventive efficacy of inositol hexaphosphate (IP6), a major constituent of high-fiber diets, against prostate tumor growth and progression in the transgenic adenocarcinoma of the mouse prostate (TRAMP) model. EXPERIMENTAL DESIGN: Beginning at 4 weeks of age, male TRAMP mice were fed 2% (w/v) IP6 in drinking water or only drinking water till 24 weeks of age, and then sacrificed. Prostate tissue was subjected to histopathologic analysis and to immunohistochemical analyses for proliferation and apoptosis. RESULTS: IP6 feeding did not show any adverse effect on fluid and diet consumption and body weight. There was a significant reduction (40%; P < 0.01) in lower urogenital tract weight in IP6-fed mice. IP6 inhibited prostate cancer progression at prostatic intraepithelial neoplasia stage and strongly reduced the incidence of adenocarcinoma (prostatic intraepithelial neoplasia/adenocarcinoma, 75:25% in the IP6 group versus 39:61% in the control group; P < 0.05). The incidences of well-differentiated and poorly differentiated adenocarcinomas in the IP6-fed group were reduced by 44% and 62%, respectively. Immunohistochemical analysis of prostate tissue showed a 26% decrease (P < 0.05) in proliferation cell nuclear antigen-positive cells and a 3.5-fold increase in apoptotic cells with no effect on Tag expression by IP6. CONCLUSIONS: These findings are both novel and highly significant in establishing for the first time that oral IP6, without any toxicity, suppresses prostate tumor growth and progression at the neoplastic stage, thereby reducing the incidence of adenocarcinoma through its antiproliferative and proapoptotic effects, and thus indicating that IP6 could have potential chemopreventive effects against human prostate cancer.     

Prevalence and characteristics of brittle diabetes in Britain

We investigated the prevalence and characteristics of 'brittle diabetes', defined as insulin-dependent diabetes mellitus associated with glycaemic instability of any type, leading to life disruption with recurrent and/or prolonged hospitalizations. A questionnaire was sent to all physicians and paediatricians running diabetic clinics in the UK, from lists held at the British Diabetic Association. A total of 414 brittle patients were reported (72% questionnaire return). Most were young (mean age +/- SD was 26 +/- 15 years), though there was a small peak at ages 60-70 years. There was an excess of females (66%) and overall clinic prevalence was 1.2 per 1000 diabetic patients and 2.9 per 1000 insulin-treated diabetic patients. On average, there was 1.0 brittle patient per diabetic clinic. The most common form of brittleness was recurrent ketoacidosis (59%), with 17% having predominant hypoglycaemia, and 24% mixed instability. Female excess was highest and mean age lowest in the recurrent ketoacidosis group, whilst the reverse was true for those with recurrent hypoglycaemia. Causes of brittleness were offered by 58% of consultants, and most (93%) considered various psychosocial problems as likely underlying factors. We conclude that brittle diabetes is a small but significant problem, currently affecting about 1 per 1000 diabetic patients. Most, but by no means all, are young females--often with recurrent ketoacidosis. Older age groups are more likely to have recurrent hypoglycaemic or mixed types of brittleness. Perceived causes of brittleness are usually psychosocial.      

Patterns of Insulin Dependence in an African Diabetic Clinic

SUMMARY Analysis of the age of onset of diabetes amongst insulin-treatedpatients in a large African diabetic clinic revealed a bimodaltype of distribution, 23 per cent having an age of onset before30 years and 77 per cent with onset at 30 years of age. All66 of the young insulin-treated group (21.7±4.8 years(mean±1 SD)), and a random selection of 50 older insulin-treatedpatients (49.7±10 years), were studied. The older groupwere better controlled (HbA₁ 8.4±1.7 per cent vs. 10.8±2.6per cent, p<0.001), on lower doses of insulin (49±23vs. 71±23 u/day, p<0.001) and had higher body massindex (26.0±5.6 vs. 21.8±3.5, p<0.001). SerumC-peptide (0.24±0.15 vs. 0.07±0.10 nmol/l, p<0.0001),and C-peptide/glucose ratio (2.57±2.65 vs. 0.56+0.98nmol/mmolx 10², p<0.001) were very significantly higher inolder patients. Patients with later onset disease thus had betterpreservation of pancreatic function, higher body mass indexand better glycaemic control on lower doses of insulin. Thesefeatures suggest that older insulin-treated patients could infact be ‘Type 2’ or non-insulin dependent patients,and the condition may be controllable with diet and/or oralhypoglycaemic agents, at least in some.     

Effect of ursolic acid on cardiac marker enzymes,lipid profile and macroscopic enzyme mapping assay in isoproterenol-induced myocardial ischemic rats

This study investigates the antihyperlipidemic effect of ursolic acid (UA) on isoproterenol (ISO) induced male albino Wistar rats. Myocardial ischemia was induced by subcutaneous injection of ISO (85 mg/kg BW) twice at an interval of 24 h, for two consecutive days. A significant increase in the activities of the serum marker enzymes [creatine kinase, creatine kinase-MB and lactate dehydrogenease (LDH)], a prominent expression of LDH 1 and LDH 2 isoenzymes, increased levels of plasma total cholesterol (TC), low density lipoprotein-cholesterol, very low density lipoprotein-cholesterol, triglycerides (TG), free fatty acids (FFA), phospholipids (PL) and atherogenic index and decreased level of high density lipoprotein-cholesterol were observed in ISO-induced rats. The levels of TC, TG and FFA increased and the level of PL decreased in the heart tissue of ISO-induced rats. Further, there was an increased DNA damage (Comet assay) and myocardium infarct size as observed by staining with triphenyltetrazolium chloride (TTC). UA was administered subcutaneously for 7 days at a dose of 40 mg/kg BW. UA administration to ischemic rats brought all these parameters to near normality showing the protective effect of UA on ISO-induced rats.     

Gallic Acid,an Active Constituent of Grape Seed Extract,Exhibits Anti-proliferative,Pro-apoptotic and Anti-tumorigenic Effects Against Prostate Carcinoma Xenograft Growth in Nude Mice

Purpose  Gallic acid, a natural agent present in a wide-range of fruits and vegetables, has been of potential interest as an anti-cancer agent; herein, we evaluated its efficacy in androgen-independent DU145 and androgen-dependent-22Rv1 human prostate cancer (PCa) cells. Materials and Methods  Cell viability was determined by MTT and apoptosis by Annexin V-PI assays. In vivo anti-cancer efficacy was assessed by DU145 and 22Rv1 xenograft growth in nude mice given normal drinking water or one supplemented with 0.3% or 1% (w/v) gallic acid. PCNA, TUNEL and CD31 immunostaining was performed in tumor tissues for in vivo anti-proliferative, apoptotic and anti-angiogenic effects of gallic acid. Results  Gallic acid decreased cell viability in a dose-dependent manner in both DU145 and 22Rv1 cells largely via apoptosis induction. In tumor studies, gallic acid feeding inhibited the growth of DU145 and 22Rv1 PCa xenografts in nude mice. Immunohistochemical analysis revealed significant inhibition of tumor cell proliferation, induction of apoptosis, and reduction of microvessel density in tumor xenografts from gallic acid-fed mice as compared to controls in both DU145 and 22Rv1 models. Conclusion  Taken together, our findings show the anti-PCa efficacy of gallic acid and provide a rationale for additional studies with this naturally-occurring agent for its efficacy against PCa.     

Silibinin Suppresses Spontaneous Tumorigenesis in <Emphasis Type="BoldItalic">APC</Emphasis><Superscript>min/+</Superscript> Mouse Model by Modulating Beta-Catenin Pathway

Purpose  

Here we assessed whether silibinin, a nontoxic chemopreventive agent, inhibits spontaneous intestinal tumorigenesis in APC ^min/+ mouse model, a genetically predisposed animal model of human familial adenomatous polyposis (FAP).     

Evidence for early and progressive ultrasonic vocalization and oromotor deficits in a PINK1 gene knockout rat model of Parkinson's disease

Parkinson's disease (PD) is a progressive neurodegenerative disease that leads to a wide range of motor and nonmotor deficits. Specifically, voice and swallow deficits manifest early, are devastating to quality of life, and are difficult to treat with standard medical therapies. The pathological hallmarks of PD include accumulation of the presynaptic protein α‐synuclein (αSyn) as well as degeneration of substantia nigra dopaminergic neurons. However, there is no clear understanding of how or when this pathology contributes to voice and swallow dysfunction in PD. The present study evaluates the effect of loss of function of the phosphatase and tensin homolog‐induced putative kinase 1 gene in rats (PINK1^–/–), a model of autosomal recessive PD in humans, on vocalization, oromotor and limb function, and neurodegenerative pathologies. Behavioral measures include ultrasonic vocalizations, tongue force, biting, and gross motor performance that are assayed at 2, 4, 6, and 8 months of age. Aggregated αSyn and tyrosine hydroxylase immunoreactivity (TH‐ir) were measured at 8 months. We show that, compared with wild‐type controls, PINK1^–/– rats develop 1) early and progressive vocalization and oromotor deficits, 2) reduced TH‐ir in the locus coeruleus that correlates with vocal loudness and tongue force, and 3) αSyn neuropathology in brain regions important for cranial sensorimotor control. This novel approach of characterizing a PINK1^–/– genetic model of PD provides the foundational work required to define behavioral biomarkers for the development of disease‐modifying therapeutics for PD patients. © 2015 Wiley Periodicals, Inc.