Nanotherapy silencing the interleukin‐8 gene produces regression of prostate cancer by inhibition of angiogenesis

Interleukin‐8 (IL‐8) is a pro‐angiogenic cytokine associated with aggressive prostate cancer (CaP). We detected high levels of IL‐8 in sera from patients with CaP compared with healthy controls and patients with benign prostatic hypertrophy. This study examines the role of IL‐8 in the pathogenesis of metastatic prostate cancer. We developed a biocompatible, cationic polylactide (CPLA) nanocarrier to complex with and efficiently deliver IL‐8 small interfering RNA (siRNA) to CaP cells in vitro and in vivo. CPLA IL‐8 siRNA nanocomplexes (nanoplexes) protect siRNA from rapid degradation, are non‐toxic, have a prolonged lifetime in circulation, and their net positive charge facilitates penetration of cell membranes and subsequent intracellular trafficking. Administration of CPLA IL‐8 siRNA nanoplexes to immunodeficient mice bearing human CaP tumours produced significant antitumour activities with no adverse effects. Systemic (intravenous) or local intra‐tumour administration of IL‐8 siRNA nanoplexes resulted in significant inhibition of CaP growth. Magnetic resonance imaging and ultrasonography of experimental animals demonstrated reduction of tumour perfusion in vivo following nanoplex treatment. Staining of tumour sections for CD31 confirmed significant damage to tumour neovasculature after nanoplex therapy. These studies demonstrate the efficacy of IL‐8 siRNA nanotherapy for advanced, treatment‐resistant human CaP.     

Serum levels of homocysteine in mice with malignant tumours

BACKGROUND:

Oxygen radicals and malondialdehyde (MDA) are tumourigenic. Homocysteine generates oxygen radicals. The possibility exists that hyperhomocysteinemia is a risk factor for cancer.

OBJECTIVE:

To investigate if serum levels of homocysteine and MDA are elevated in mice with malignant tumours.

METHODS:

Levels of serum homocysteine and MDA were estimated in 22 control and 22 tumour-bearing Balb/c mice.

RESULTS:

Serum homocysteine levels in control and tumour-bearing mice were 3.01±0.26 μmol/L and 4.05±0.46 μmol/L, respectively. The serum levels of MDA were 6.23±0.72 nmol/mL and 11.60±1.72 nmol/mL, respectively, in control and tumour-bearing mice.

CONCLUSION:

These results suggest that cancer in mice is associated with an increase in serum levels of homocysteine and the lipid peroxidation product MDA. It is, however, not known if this rise in homocysteine and MDA is due to cancer or if this rise causes cancer.     

Comparative assessment of dentition status among poliomyelitis children in Udaipur,India

To determine and compare the dental caries experience and treatment needs of children with Poliomyelitis at Udaipur, India. Total sample comprised of 344 children with Poliomyelitis (upper limb disability: 33.4%; lower limb disability: 33.7%; both upper and lower limb disability: 32.8%) in the age group of 12–15 years. Clinical examination included recording Dentition Status and Treatment Needs. Chi‐square test, Analysis of variance (ANOVA), multiple logistic and stepwise linear regressions were used for statistical analysis. The mean decayed, missing, filled teeth (DMFT) score (4.47 ± 3.09) was found to be highest among children with Poliomyelitis having both upper and lower limb impairment (p < .05). Stepwise and logistic regression analysis showed that the best predictors for dental caries were disability, socioeconomic status and snacks in between meals. A significant relationship of dental caries with limb involved in impairment draws immediate attention for a planned approach in improving the oral health.     

Blood volume monitoring in intermittent hemodialysis for acute renal failure

BACKGROUND: Although hypotension commonly accompanies intermittent hemodialysis for acute renal failure (ARF) in the intensive care unit (ICU), little is known about how it may be prevented. Online relative blood volume (RBV) monitoring has been used to reduce hypotension in chronic hemodialysis, but is of unproven benefit in ARF. This study tested the hypothesis that hypotension is predictable using online RBV monitoring in patients dialyzed for ARF in an ICU setting. METHODS: The primary definition of hypotension was mean arterial pressure (MAP) <70 mm Hg; systolic blood pressure (SBP) <100 mm Hg was used as a secondary outcome. Fifty-seven treatments were prospectively studied in twenty consecutive adult patients treated with intermittent hemodialysis. RBV was continuously measured using the Hemoscan device (Gambro). RESULTS: Hypotension occurred in 30% of treatments as defined by MAP, and 18% as defined by SBP. There was no evidence of patient-specific or universal RBV thresholds that were associated with hypotension. Analysis using the kappa statistic showed that concordance of RBV and hypotension (that is, RBV falling prior to hypotensive episodes rather than rising or remaining stable) was no greater than chance. RBV and rate of change in RBV slopes did not predict hypotension as a dichotomous outcome, and were not correlated with MAP or SBP whether autocorrelation was corrected for or neglected. Substituting rate of change in RBV (RBV slopes) for absolute RBV values did not improve predictive power. CONCLUSIONS: These results suggest that strategies based on online RBV monitoring are unlikely to reduce hypotension in intermittent hemodialysis for ARF that is delivered through central venous catheters.     

Secondary generalized dystonia without basal ganglia damage

We report the case of a woman who developed generalized dystonia, severe cognitive deficits and dysphagia following an overdose of the hypoglycaemic drug, sulphonylurea. The MRI reveals frontal and temporal lobe atrophy, but no evidence of damage to the basal ganglia. This case adds to the small number of previously reported cases with secondary dystonia seemingly due to cortical rather than subcortical damage.     

What does the marriage of Open Access with online publication bring?

Open Access online publishing is the trend of the future for unrestricted rapid and international dissemination of knowledge. Several journals are published on acquired immune deficiency syndrome (AIDS) research, but none of them appear to be Open Access. To eliminate or to abate the scourge of AIDS, it is important that the knowledge acquired through research be disseminated as soon as possible. The Open Access journal, AIDS Research and Therapy, is intended to fill this knowledge gap by online publication of basic, preclinical, and clinical research articles.     

C-reactive protein increases oxygen radical generation by neutrophils

C-reactive protein (CRP) has been suggested to play a role in the pathogenesis of atherosclerosis. Neutrophil respiratory burst and levels of CRP are increased during infection. The increase in the neutrophil respiratory burst may be due to factors that are elevated in infection, such as cytokines, tumor necrosis factor, platelet-activating factor, and CRP. The direct effect of CRP on the release of oxygen radicals by neutrophils is not known. This investigation was made to determine if CRP affects the generation of oxygen radicals by neutrophils and if this effect is blocked by antioxidants. The effect of various concentrations (1 to 200 microg/mL blood) of CRP on the generation of oxygen radicals by neutrophils was measured as luminol-dependent chemiluminescence (chemiluminescent activity) on a luminometer (Auto Lumat LB953, EG & G Berthold, Gaithersburg, MD). The unit of chemiluminescent activity is the relative light unit and was expressed as relative light unit/white blood cell (RLU/WBC). Chemiluminescent activity of blood without CRP was slightly higher than that of buffer with or without CRP. CRP markedly increased the chemiluminescent activity of blood. There was no significant change in the chemiluminescent activity of WBCs with 1 microg/mL of CRP. The chemiluminescent activity increased significantly with higher concentrations of CRP. The percent increases in the chemiluminescent activity with 2, 5, 10, 25, 50, 100 and 200 microg/mL of CRP were 45%, 72%, 50%, 70%, 52%, 67%, and 68% respectively. Antioxidants (superoxide dismutase, catalase, and dimethylthiourea) blocked CRP-induced oxygen radicals by WBCs. These results suggest that CRP increases the generation of oxygen radicals from the WBCs. CRP-induced atherosclerosis may be mediated through generation of oxygen radicals by neutrophils.     

Serum interferon inhibitor declines in patients with HIV-1 infection after a change in antiretroviral therapy

An inhibitor of interferon antiviral activity, which is absent in healthy HIV-seronegative persons, was detected in the sera of all 29 HIV-seropositive study participants. The relationship of the level of interferon inhibitor to CD4 count and HIV-RNA copy number was statistically significant in distinct models. Levels of interferon inhibitor declined by an average of 41-60% in patients who underwent a change in anti-retroviral therapy. Interferon inhibitor levels appear to decline as CD4 cell count rises and HIV-RNA levels fall. This suggests that interferon inhibitor may have a significant role in the host immune response to HIV infection.