p21/Cip1 and p27/Kip1 Are essential molecular targets of inositol hexaphosphate for its antitumor efficacy against prostate cancer.

Inositol hexaphosphate (IP6) causes G(1) arrest and increases cyclin-dependent kinase inhibitors p21/Cip1 and p27/Kip1 protein levels in human prostate cancer (PCa) DU145 cells lacking functional p53. However, whether cyclin-dependent kinase inhibitor I induction by IP6 plays any role in its antitumor efficacy is unknown. Herein, we observed that either p21 or p27 knockdown by small interfering RNA has no considerable effect on IP6-induced G(1) arrest, growth inhibition, and death in DU145 cells; however, the simultaneous knockdown of both p21 and p27 reversed the effects of IP6.

Growth inhibition and regression of lung tumors by silibinin: modulation of angiogenesis by macrophage-associated cytokines and nuclear factor-kappaB and signal transducers and activators of transcription 3.

The latency period for lung tumor progression offers a window of opportunity for therapeutic intervention. Herein, we studied the effect of oral silibinin (742 mg/kg body weight, 5 d/wk for 10 weeks) on the growth and progression of established lung adenocarcinomas in A/J mice. Silibinin strongly decreased both tumor number and tumor size, an antitumor effect that correlates with reduced antiangiogenic activity.

Multitargeted therapy of cancer by silymarin.

Silymarin, a flavonolignan from milk thistle (Silybum marianum) plant, is used for the protection against various liver conditions in both clinical settings and experimental models. In this review, we summarize the recent investigations and mechanistic studies regarding possible molecular targets of silymarin for cancer prevention. Number of studies has established the cancer chemopreventive role of silymarin in both in vivo and in vitro models.

Diabetic retinopathy: an update.

Diabetes mellitus is a major cause of avoidable blindness in both the developing and the developed countries. Significant technological advances have taken place to improve the diagnostic accuracy of diabetic retinopathy. In the last three decades, the treatment strategies have been revised to include, besides laser photocoagulation, early surgical interventions and pharmacotherapies.

Rhizoremediation of metals: harnessing microbial communities.

With the increasing successful stories of decontamination, different strategies for metal remediation are gaining importance and popularization in developing countries. Rhizoremediation, is one such promising option that harnesses the impressive capabilities of microorganisms associated with roots to degrade organic pollutants and transform toxic metals. Since it is a plant based in-situ phytorestoration technique it is proven to be economical, efficient and easy to implement under field conditions.

Severe phenytoin toxicity in a CYP2C9*3*3 homozygous mutant from India.

The authors report an Indian adult female patient with a history of generalized tonic clonic seizures who developed severe features of phenytoin (DPH) toxicity on therapeutic dosage of this antiepileptic drug. Administration of 300 mg/day of DPH in this patient resulted in toxic symptoms associated with an excessive serum DPH concentration of 33 microg/ml. The PCR-RFLP analysis revealed a homozygosity involving CYP2C9*3*3.

Circulating DNA: a potential marker of sickle cell crisis.

Free circulating DNA is present in the plasma of healthy subjects, and is elevated in conditions characterized by increased cell death, such as cancer and physical trauma. Analysis of circulating DNA in plasma could provide a useful biomarker in sickle cell disease (SCD) in view of the increased cell turnover through chronic ongoing haemolysis, recurrent vaso-occlusion and inflammation. Plasma DNA was determined by real-time quantitative polymerase chain reaction (PCR) amplification of the beta-globin gene (HBB) in 154 patients with SCD [105 haemoglobin (Hb)SS, 46 HbSC and three HbS/beta(0) thalassaemia] and 53 ethnically matched controls.

Increase in the relative expression of tau with four microtubule binding repeat regions in frontotemporal lobar degeneration and progressive supranuclear palsy brains.

Some cases of familial frontotemporal dementia (FTD) leading to frontotemporal lobar degeneration (FTLD) are caused by mutations in tau on chromosome 17 (FTDP-17). Certain mutations alter the ratio between four (4R tau) and three (3R tau) repeat tau isoforms whereas cases with progressive supranuclear palsy (PSP) and corticobasal degeneration (CBD) mainly have 4R tau brain pathology. We assessed tau mRNA and protein levels in frontal cortex from 15 sporadic FTLD, 21 PSP, 5 CBD, 15 Alzheimer's disease (AD) and 16 control brains.

Revisiting niacin: reviewing the evidence.

Atherogenic dyslipidemia, defined by a cluster of lipoprotein abnormalities, including low high-density lipoprotein cholesterol (HDL-C) and elevated serum triglycerides, represents an important potential target for reducing cardiovascular risk. This has paved the way for revisiting niacin as a therapy in preventing progression of atherosclerosis. Niacin remains the safest and most effective agent for raising HDL-C and is a logical choice to target atherogenic dyslipidemia.

Vitrectomy for circumscribed choroidal hemangioma with exudative retinal detachment refractory to transpupillary thermotherapy.

We report successful surgical management of a circumscribed choroidal hemangioma with exudative retinal detachment refractory to transpupillary thermotherapy (TTT). A 33-year-old man with symptomatic serous macular detachment in the left eye (Snellen acuity: 20/200) secondary to a paramacular choroidal hemangioma was treated with TTT. The nonresponsive detachment was subsequently managed by vitrectomy, endophotocoagulation and silicon-oil tamponade.

Expression of APP pathway mRNAs and proteins in Alzheimer's disease.

In both trisomy 21 and rare cases of triplication of amyloid precursor protein (APP) Alzheimer's disease (AD) pathological changes are believed to be secondary to increased expression of APP. We hypothesized that sporadic AD may also be associated with changes in transcription of APP or its metabolic partners. To address this issue, temporal neocortex of 27 AD and 21 non-demented control brains was examined to assess mRNA levels of APP isoforms (total APP, APP containing the Kunitz protease inhibitor domain [APP-KPI] and APP770) and APP metabolic enzymatic partners (the APP cleaving enzymes beta-secretase [BACE] and presenilin-1 [PS-1], and putative clearance molecules, low-density lipoprotein receptor protein [LRP] and apolipoprotein E [apoE]).

Software for reading and grading diabetic retinopathy: Aravind Diabetic Retinopathy Screening 3.0.

Objective: To evaluate the validity and reproducibility of software for reading digital images and grading diabetic retinopathy.

Research Design And Methods: A prospective, comparative observational study was conducted on a series of patients with type 2 diabetes who presented at the retina clinic of a tertiary care center in India. A total of 210 eyes of 105 patients were allocated to one of three ophthalmologists, who performed dilated indirect and direct ophthalmoscopy and subsequently assessed the digital images of the same group of patients who were masked to the patient's identity.

Cyclic monophosphate prodrugs of base-modified 2'-C-methyl ribonucleosides as potent inhibitors of hepatitis C virus RNA replication.

A new series of heterobase-modified 2'-C-methyl ribonucleosides was synthesized and tested as inhibitors of hepatitis C virus (HCV) RNA replication. The nucleosides showed a weak inhibitory activity in a HCV replicon system (EC(50)=92 microM) and did not exhibit any cytotoxicity (CC(50)>300 microM). Cyclic monophosphate (cMP) prodrugs of the same nucleosides were synthesized and also tested in the HCV replicon system.

6-Hydrazinopurine 2'-methyl ribonucleosides and their 5'-monophosphate prodrugs as potent hepatitis C virus inhibitors.

A series of 6-hydrazinopurine 2'-methyl ribonucleosides was synthesized and tested for its inhibitory activity against the hepatitis C virus (HCV). The lack of antiviral activity of these nucleosides was associated with a poor affinity for adenosine kinase, which prompted us to synthesize several of their 5'-monophosphate prodrugs. Some of these prodrugs exhibited more than 1000-fold improvement in anti-HCV activity when compared to their parent nucleosides (EC(50) of 24 nM vs 92 microM for the parent).

Acute myeloid leukaemia presenting with mediastinal myeloid sarcoma: report of three cases and review of literature.

Although myeloid sarcomas (MS) are frequently associated with acute myeloid leukaemia (AML), the occurrence of mediastinal MS is a much rarer event. The authors describe a distinct group of three AML patients with mediastinal MS and complex cytogenetics presenting at their centre over a 7-year period. Clinical features consistent with superior vena caval obstruction were noted at presentation in two of the three patients.

Pigmented epiretinal membranes caused by RPE migration: OCT-based observational case reports.

Epiretinal membranes are cellular sheets on the retinal surface that are formed due to varied etiologies. We present two observational case reports to demonstrate the transretinal migration of the retinal pigment epithelium in pigmented idiopathic epiretinal membranes using optical coherence tomography.

Allele and genotype frequency of MDR1 C3435T in Tamilian population.

The allele and genotype frequencies of MDR1 C3435T polymorphism were determined in 185 unrelated healthy Tamilians. The genomic DNA was extracted from peripheral leucocytes using phenol chloroform method and genotyped by PCR-RFLP method. The frequencies of MDR1 C3435 and T3435 alleles in Tamilian population were 0.

Diffuse unilateral subacute neuroretinitis with unusual findings.

Purpose: To report two cases of diffuse unilateral subacute neuroretinitis (DUSN) with unusual findings.

Design: Observational and interventional case series.

Methods: Two patients with DUSN were found to have the unusual findings of a large live worm in one eye and macular cyst in the other.

Synthesis of pyrrolo[2,3-d]pyrimidine nucleoside derivatives as potential anti-HCV agents.

Several Toyocamycin (4) analogues were examined for their ability to inhibit HCV RNA in a replicon assay. Among the compounds examined 4-methylthio (18) and 5-carboxamide oxime derivatives (23 and 27) of Toyocamycin were found to have good activity and selectivity.

Successful treatment of refractory angioimmunoblastic T-cell lymphoma with thalidomide and dexamethasone.

Angioimmunoblastic T cell lymphoma (AITL) is a peripheral T-cell lymphoma characterized morphologically by lymphadenopathy with a polymorphic infiltrate, marked vascular and follicular dendritic cell proliferation. Patients usually present with advanced disease and the overall prognosis is poor. While intensive chemotherapy has been shown to induce complete remissions in 50-70% of patients, the majority of patients subsequently relapse.

No alteration in tau exon 10 alternative splicing in tangle-bearing neurons of the Alzheimer's disease brain.

Defective splicing of tau mRNA, promoting a shift between tau isoforms with (4R tau) and without (3R tau) exon 10, is believed to be a pathological consequence of certain tau mutations causing frontotemporal dementia. By assessing protein and mRNA levels of 4R tau and 3R tau in 27 AD and 20 control temporal cortex, we investigated whether altered tau splicing is a feature also in Alzheimer's disease (AD). However, apart from an expected increase of sarcosyl-insoluble tau in AD, there were no significant differences between the groups.

Coordinated expression of caspase 8, 3 and 7 mRNA in temporal cortex of Alzheimer disease: relationship to formic acid extractable abeta42 levels.

Recent studies support the hypothesis that Alzheimer disease (AD)-associated amyloid-beta protein (Abeta) may induce apoptosis mediated by a caspase cascade. To assess whether mRNA levels of caspase-3, 7, 8 and 9 change in AD brain, and whether these changes correlate with neurofibrillary tangles, Abeta40 or Abeta42 protein levels or senile plaques, 25 AD and 21 non-demented control brains were examined. Elevated mRNA levels of caspases-7 and 8 measured by a quantitative PCR method were observed in the AD temporal neocortex as compared to the control brains.