Reduction of cerebral infarct volume by apocynin requires pretreatment and is absent in Nox2-deficient mice

Background and purpose:

Reactive oxygen species (ROS) derived from Nox2-containing reduced form of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activity is reportedly detrimental in cerebrovascular disease. However, ROS generation by other Nox isoforms may have a physiological role. No Nox2-selective inhibitors have yet been identified, and thus it is unclear whether isoform non-selective Nox inhibitors would necessarily improve outcome after stroke. We assessed the effect of apocynin on cerebrovascular ROS production and also on outcome following cerebral ischaemia when administered either before ischaemia or after cerebral reperfusion. The involvement of Nox2-containing NADPH oxidase in the effects of apocynin was assessed using Nox2^−/− mice.

Experimental approach:

Transient cerebral ischaemia was induced by 0.5 h middle cerebral artery occlusion followed by 23.5 h reperfusion. Mice received apocynin (2.5 mg·kg⁻¹, i.p.) either 0.5 h before ischaemia or 1 h after reperfusion. In situ superoxide production after cerebral ischaemia-reperfusion was measured in brain sections of wild-type mice at 24 h using dihydroethidium fluorescence.

Key results:

Treatment with apocynin 0.5 h before ischaemia reduced total infarct volume, neurological impairment and mortality in wild-type but not Nox2^−/− mice. Conversely, treatment with apocynin 1 h after initiation of reperfusion had no protective effect. Cerebral ischaemia and reperfusion increased superoxide production in the brain at 24 h, and pretreatment but not posttreatment with apocynin reduced superoxide levels.

Conclusions and implications:

Apocynin improves outcome following stroke when administered before ischaemia in wild-type but not Nox2^−/− mice.     

Immunological effect of aqueous extract of Vernonia amygdalina and a known immune booster called immunace® and their admixtures on HIV/AIDS clients: a comparative study

Objective

To investigate the immunological effect of Vernonia amygdalina (V. amygdalina) leaf extract and immunace^® on HIV infected patients taking highly active antiretroviral therapy.

Methods

Fresh V. amygdalina leaves were collected within Nsukka area in Enugu State. The leaves were rinsed with distilled water. Two handful of cleaned fresh leaves were soaked in 200 mL water and squeezed gently by hand to a mixture. Clients were divided into four groups and each group was given different combination. They took the medication for four weeks. The immune effect was tested against marketed immune booster in some retroviral clients.

Results

The mean absolute CD4 count was increased in the client who took the extract or supplement. And the clients who took both the extract and supplement had a greater increase in the CD4 count. The increased CD4 was significant as compared with the control group (P<0.05). The skin rashes were also improved in the entire groups.

Conclusions

It can be concluded that the aqueous extract of V. amygdalina and immunace or both have immunological effect on HIV infected patients. Therefore, we suggest that the V. amygdalina extract or immunace or both could be used as adjuvant in the management of HIV/AIDS clients.     

Palpable masses in the prostate: superior accuracy of US-guided biopsy compared with accuracy of digitally guided biopsy

The accuracies of digitally guided biopsy versus ultrasound (US)-guided biopsy of the prostate were compared in 112 consecutive men with palpable prostatic lesions who had previously undergone conventional digitally guided biopsy and in which the results were negative for carcinoma. US-guided biopsies were performed with either the transperineal (n = 51) or transrectal (n = 61) approach, by means of previously described methods. All US-guided biopsies were performed within 3 months after the most recent conventional biopsy. In 44 patients (39.3%) with negative results of conventional biopsies, the results of US-guided biopsy revealed cancer. The transrectal and transperineal digitally guided biopsies were equally inaccurate, and the transrectal and transperineal US-guided biopsies showed no statistically significant differences in accuracy. The patients accepted and tolerated both US techniques equally well; neither technique was associated with significant complications. It is concluded that all patients with a palpable nodule should undergo US-guided biopsy if the result of conventional digitally guided biopsy is negative for cancer and the diagnostic US scan suggests an abnormality.     

Evaluation of abdominal trauma by computed tomography

Computed tomography (CT) was used in the evaluation of 100 patients suffering abdominal trauma. The type of trauma was blunt in 78 patients, penetrating in eight, and iatrogenic in 14. Forty per cent of cases had normal CT scans, while 60% showed substantial abdominal or retroperitoneal injuries. Surgery, clinical follow-up, and repeated radiologic examinations confirmed the accuracy of CT, and there were no cases in which medical or surgical management was inappropriately guided by CT. A wide variety of injuries was detected, including 19 splenic, eight hepatic, six pancreatic, 13 renal, 13 retroperitoneal or abdominal wall, and one intraperitoneal. CT has major advantages over plain radiography, radionuclide imaging, and angiography in assessment of trauma-induced injuries.     

Protective Effect of Salvianolic Acid A on Brain Endothelial Cells after Treatment with Deprivation and Reperfusion of Oxygen-glucose

Objective Salvianolic acid A(SAA) has a significant protective effect on ischemia/reperfusion injury of brain. However, it is not clear for SAA to exert its cerebral protection by targeting at the microvascular endothelial cells of blood brain barrier(BBB). Our previous study demonstrated that SAA could hardly pass through the BBB. This present study was therefore designed to investigate the protective effect of SAA on brain microvascular endothelial cells(BMECs) induced by deprivation and reperfusion with oxygen-glucose. Methods Rat BMECs were treated with oxygen glucose deprivation(OGD), followed by reperfusion(OGD/R). Cell viability was assessed by MTT and the content of reactive oxygen species(ROS) in cells after OGD/R in the absence or presence of SAA. GC-MS based metabolomic platform was applied to evaluate the regulation of SAA on the cellular metabolic perturbation induced by OGD/R. Results OGD/R significantly increased the production of intracellular reactive oxygen species(ROS), and decreased the activity of cells. SAA significantly reduced ROS and improve the cell viability. Metabolomic study revealed distinct perturbation of metabolic pathways of energy metabolism in the BMEC induced by OGD/R, while SAA significantly regulated the perturbed metabolism involved in energy metabolism pathways, especially for intermediates in TCA cycle. Conclusion SAA shows protective effects on BMECs involved in central nervous system.     

An Inhalation Device for Exposing Eats to Cigarette Smoke

With an inhalation device for exposing small animals to fresh cigarette smoke, more accurate duplication of the physical and chemical characteristics of human cigarette smoking is achieved than is possible with the devices or chambers described in the literature. The reproducibility of the device was tested by measuring the polonium 210 deposition on filters and in the lungs of rats when labeled cigarettes were smoked by the device. With minor modifieations, the device would be usable for a variety of multistress inhalation exposures and for any of several species of small animals.     

Early CD34high cells can be separated into KIThigh cells in which transforming growth factor-beta (TGF-beta) downmodulates c-kit and KITlow cells in which anti-TGF-beta upmodulates c-kit

We have previously shown that early human CD34high hematopoietic progenitors are maintained quiescent in part through autocrine transforming growth factor-beta 1 (TGF-beta 1). We also demonstrated that, in the presence of interleukin-3, interleukin-6, granulocyte colony-stimulating factor, and erythropoietin, TGF-beta 1 antisense oligonucleotides or anti-TGF-beta serum have an additive effect with KIT ligand (Steel factor [SF]), which suggests that they control different pathways of regulation in these conditions. This finding also suggests that autocrine TGF-beta 1 might suppress c-kit expression in primitive human hematopoietic progenitors. We have now distinguished two subpopulations of CD34high cells. One subpopulation expresses a c- kit mRNA that can be downmodulated by exogenous TGF-beta 1 within 6 hours. Another subpopulation of early CD34high cells expresses a low or undetectable level of c-kit mRNA, but its expression can be upmodulated within 6 hours by anti-TGF-beta. These effects disappear 48 hours after induction and cannot be maintained longer than 72 hours, even if TGF- beta 1 or anti-TGF-beta serum are added every day. Similar kinetics, although delayed, are observed with KIT protein expression. On the contrary, no specific effect of TGF-beta 1 was observed on c-fms, GAPDH, and transferrin receptor gene expression in these early progenitors. These results clarify the complex interaction between TGF- beta 1 and SF in normal early hematopoietic progenitors. SF does not switch off the TGF-beta 1 inhibitory pathway. Autocrine TGF-beta 1 appears to maintain these cells in a quiescent state, suppressing cell division by downmodulating the receptor of SF, a key cytokine costimulator of early progenitors.