Protection against hydrogen peroxide induced oxidative damage in rat erythrocytes by Mangifera indica L. peel extract

Phytochemicals such as polyphenols and carotenoids are gaining importance because of their contribution to human health and their multiple biological effects such as antioxidant, antimutagenic, anticarcinogenic and cytoprotective activities and other therapeutic properties. Mango peel is a major by-product in pulp industry and it contains various bioactive compounds like polyphenols, carotenoids and others. In the present study, the protective effect of peel extracts of unripe and ripe mango fruits of two varieties namely, Raspuri and Badami on hydrogen peroxide induced hemolysis, lipid peroxidation, degradation of membrane proteins and its morphological changes are reported. The oxidative hemolysis of rat erythrocytes by hydrogen peroxide was inhibited by mango peel extract in a dose dependent manner. The IC₅₀ value for lipid peroxidation inhibition on erythrocyte ghost membrane was found to be in the range of 4.5–19.3 μg gallic acid equivalents. The mango peel extract showed protection against membrane protein degradation caused by hydrogen peroxide. Morphological changes to erythrocyte membrane caused by hydrogen peroxide were protected by mango peel extract. The results demonstrated that mango peel extracts protected erythrocytes against oxidative stress and may impart health benefits and it could be used as a valuable food ingredient or a nutraceutical product.     

Gene expression profile in obesity and type 2 diabetes mellitus

Obesity is an important component of metabolic syndrome X and predisposes to the development of type 2 diabetes mellitus. The incidence of obesity, type 2 diabetes mellitus and metabolic syndrome X is increasing, and the cause(s) for this increasing incidence is not clear. Although genetics could play an important role in the higher prevalence of these diseases, it is not clear how genetic factors interact with environmental and dietary factors to increase their incidence. We performed gene expression profile in subjects with obesity and type 2 diabetes mellitus with and without family history of these diseases. It was noted that genes involved in carbohydrate, lipid and amino acid metabolism pathways, glycan of biosynthesis, metabolism of cofactors and vitamin pathways, ubiquitin mediated proteolysis, signal transduction pathways, neuroactive ligand-receptor interaction, nervous system pathways, neurodegenerative disorders pathways are upregulated in obesity compared to healthy subjects. In contrast genes involved in cell adhesion molecules, cytokine-cytokine receptor interaction, insulin signaling and immune system pathways are downregulated in obese. Genes involved in signal transduction, regulation of actin cytoskeleton, antigen processing and presentation, complement and coagulation cascades, axon guidance and neurodegenerative disorders pathways are upregulated in subjects with type 2 diabetes with family history of diabetes compared to those who are diabetic but with no family history. Genes involved in oxidative phosphorylation, immune, nervous system, and metabolic disorders pathways are upregulated in those with diabetes with family history of diabetes compared to those with diabetes but with no family history. In contrast, genes involved in lipid and amino acid pathways, ubiquitin mediated proteolysis, signal transduction, insulin signaling and PPAR signaling pathways are downregulated in subjects with diabetes with family history of diabetes. It was noted that genes involved in inflammatory pathway are differentially expressed both in obesity and type 2 diabetes. These results suggest that genes concerned with carbohydrate, lipid and amino acid metabolic pathways, neuronal function and inflammation play a significant role in the pathobiology of obesity and type 2 diabetes.     

Chromosomal breakage in myelodysplatic syndrome.

The myelodysplastic syndrome (MDS) represents a group of clonal hematological disorders characterized by progressive cytopenia reflecting defects in erythroid, myeloid and mega karyocytic maturation. The incidence of MDS is greter in older age groups. Detailed studies on MDS from India are not available. Cytogenetic study using GTG-banding and FISH revealed 54.5% clonal chromosomal abnormalities. We have carried out chromosomal breakage study from peripheral blood cultures induced with mitomycin C, in karyotypically normal MDS (49) and 15 (30.6%) showed significant (p < 0.001) increase in chromosome damage compared to controls. Among 22 occupationally exposed MDS, 6 (27.3%) showed a high frequency of chromosome breakage while in the non-exposure (n=27) group, high chromosome breakage was noted in 9 (33.3% ) MDS patients. Our results suggest that the high chromosome damage may be due to acquired Fanconi anemia which leads to multiple defects in chromosomes and clonal chromosome anomalies.     

Phase I study of epirubicin, cisplatin and capecitabine plus matuzumab in previously untreated patients with advanced oesophagogastric cancer

To evaluate the safety, tolerability, efficacy, pharmacokinetics and pharmacodynamics of the humanised antiepidermal growth factor receptor monoclonal antibody matuzumab combined with epirubicin, cisplatin and capecitabine (ECX) in patients as first-line treatment for advanced oesophagogastric cancer that express epidermal growth factor receptor (EGFR). This was a phase I dose escalation study of matuzumab at 400 and 800 mg weekly and 1200 mg every 3 weeks combined with ECX (epirubicin 50 mg m⁻², cisplatin 60 mg m⁻² on day 1 and capecitabine 1000 mg m⁻² daily). Patients were treated until disease progression, unacceptable toxicity or for a maximum of eight cycles. Twenty-one patients were treated with matuzumab at three different dose levels (DLs) combined with ECX. The main dose-limiting toxicity (DLT) was grade 3 lethargy at 1200 mg matuzumab every 3 weeks and thus 800 mg matuzumab weekly was the maximum-tolerated dose (MTD). Other common toxicities included rash, nausea, stomatitis and diarrhoea. Pharmacokinetic evaluation demonstrated that the coadministration of ECX did not alter the exposure of matuzumab. Pharmacodynamic studies on skin biopsies demonstrated inhibition of the EGFR pathway. Objective response rates of 65% (95% confidence interval (CI): 43–82), disease stabilisation of 25% (95% CI: 11–47) and a disease control rate (CR+PR+SD) of 90% were achieved overall. The MTD of matuzumab in combination with ECX was 800 mg weekly, and at this DL it was well-tolerated and showed encouraging antitumour activity. At the doses evaluated in serial skin biopsies, matuzumab decreased phosphorylation of EGFR and MAPK, and increased phosphorylation of STAT-3.     

香椿子抗凝血作用的实验研究

目的:观察香椿子的抗凝血作用.方法:采用小鼠毛细玻管法及玻片法观察香椿子对小鼠凝血时间的影响.以断尾法观察香椿子对小鼠出血时间的影响.对小鼠血浆复钙时间(Re-calcium Time,RT)、大鼠凝血酶原时间(PT)、大鼠活化部分凝血活酶时间(APTT)、大鼠凝血酶时间(TT)进行测定来观察香椿子对这些指标的影响.结果:①毛细玻管法:香椿子1000、1200、1400、1600mg/kg剂量组与生理盐水组比较能显著延长小鼠的凝血时间.②玻片法:香椿子400、1000mg/kg剂量组与生理盐水组比较能显著延长小鼠的凝血时间,但高剂量组与生理盐水组没有明显差异.③对小鼠出血时问的影响:香椿子三个剂量组的出血时间均明显长于生理盐水组.④对血浆复钙时间的影响:香椿子1000、1400mg/,kg剂量组与生理盐水组比较,均明显延长了血浆复钙时问.400mg/kg剂量组与生理盐水组没有明显差异.⑤对大鼠PT、APTT及,TT的影响:香椿子三个剂量组均显著延长了大鼠PT及TT.980mg/kg剂量组与生理盐水组比较能显著延长大鼠的APTT.结论:香椿子有较强的抗凝血作用.     

利心丸对小鼠缺氧耐受的影响及机理

目的研究利心丸对小鼠缺氧耐受的影响并初步探讨其机理。方法小鼠随机分生理盐水(每天20g/kg)组、心得安(每天0.16g/kg)组、利心丸高剂量(每天5g/kg)和低剂量(每天1g/kg)组,连续给药5天并于末次给药1h后测定小鼠缺氧耐受能力以及血清乙酰胆碱酯酶(T-ChE)和总抗氧化能力(T-AOC)。结果利心丸低剂量组耗氧率和心得安组均较生理盐水组显著降低(P<0.05或0.01);心得安组T-ChE活性较生理盐水组显著增高(P<0.01);心得安组和利心丸高剂量组T-AOC均较生理盐水组显著增高(P均<0.01)。结论利心丸低剂量能提高小鼠抗常压的缺氧耐受能力,可能与提高机体总抗氧化能力有关。     

Intranasal Tat Alters Gene Expression in the Mouse Brain

Intranasal (IN) delivery of HIV-1 Tat in aging mice was investigated as a possible model for HIV-1 infection in the brain. After IN administration, the distribution of [¹²⁵I]-labeled Tat in the brains of Swiss Webster mice was evaluated by autoradiography and gamma counting. [¹²⁵I]-labeled Tat was detected at the highest concentrations in the olfactory bulb, cervical nodes, and trigeminal nerve tract. In another experiment, APPSw transgenic mice were used to model chronic Tat exposure. The mice were treated intranasally with 6 μg Tat (n = 4) or vehicle (n = 4) three times per week for 4 weeks. Total RNA was isolated from the frontal cortex, and differential gene expression analysis was performed using gene microarrays. Gene ontology profiles indicated innate immunity, inflammatory and apoptotic responses. Five genes of interest in the Tat-treated mice that were significantly elevated in the microarrays were validated by RT-PCR. One gene, the Toll-like receptor 9 (Tlr9), has previously been shown to activate signaling cascades leading to innate immunity and enhanced HIV-1 gene expression. A second gene, Fas, plays a key role in neuroinflammation. Two cysteine-rich cytokines associated with chemotaxis were elevated: MCP-1 (Ccl2), which is chemotactic for monocytes, and Ccl17 (TARC), which is chemotactic for lymphocytes. Finally, the gene sestrin was significantly elevated and has been associated with oxidative stress, in particular amyloid beta-induced oxidative stress. This IN Tat model of neuroinflammation may be useful to study HIV-1-induced neurodegeneration. This paper was presented at an NIMH workshop “HIV Preclinical–Clinical Therapeutics Research Meeting”, May 5–16, 2006.     

Meniere's disease: An immune complex-mediated illness?

The cause of Menière's disease is unknown. Recent clinical research suggests that one etiology is immune-mediated damage to the inner ear. The diagnosis of autoimmune Menière's syndrome is largely based on history, response to steroids, or results of nonspecific laboratory tests such as serological studies. Polyethylene glycol (PEG) assay was used to determine levels of circulating immune complexes (CIC) in 30 patients with Menière's disease and 20 control subjects. Patients with Menière's disease had a statistically significant elevation of serum circulating immune complexes when compared to the control group. This suggests that CICs may be involved in the pathogenesis of Menière's disease, either as a direct cause of damage, or as a by-product of an underlying autoimmune abnormality. Therapeutic implications include use of plasmapheresis to remove the complexes or CIC monitoring to serve as a marker for treatment efficacy.