An improved method for injection of bolus doses of drugs into the perfusion circuit of isolated perfused rat kidney utilizing a six-port injection valve

The isolated perfused rat kidney experiment was introduced in 1959 for studying the regulation of renal blood flow and is recognized as a valuable preparation for studying physiological and biochemical aspects of renal function such as hemodynamics, glomerular filtration rate (GFR) and overall handling of fluids. Dose-response curves are obtained by injection of bolus doses of drugs into the perfusion line. However current injection methods can cause several problems such as low reproducibility and altered baseline pressure. The aim of the present work is to develop a simple method of introducing the drug into the perfusion circuit which is free from these aberrations. This was achieved using a six-way injection valve placed in the perfusion circuit, just before the kidney. To assess the reproducibility of this method, 400 μL epinephrine (10-7 M) was injected seven times into an isolated perfused rat kidney. The mean peak pressure rise (mmHg) was 30.3±0.6, 28.5±0.8 and 27.1±0.6 at 100, 120 and 140 mmHg base perfusion pressures respectively. Base pressure returned to pre-injection levels under all conditions tested. Low standard deviation of pressure maxima indicates the high reproducibility of this method while multiple injections can be made in a relatively shorter time. This method can be applied to all organ perfusion setups such as isolated hind limb, tail, arteries and arterioles

An image processing technique for diagnosis of Alzheimer's disease

<ul><li><strong>BACKGROUND</strong>: Patients with Alzheimer's disease (AD) reportedly hibit hypersensitivity to much diluted tropicam solution (0.005%), a M4 muscarinic receptor antagonist. Therefore aocular application of 0.005% tropicamide ma be useful for screening dementia. The aim of this study was to simplify the pupil response test by using a new image analyzing system, which consists of a cheap, simple, and easy to use web-camera and a computer.</li><li><strong>METHODS</strong>: Intraocular tropicamide of 0.005% concentration was administered in 3 groups: Alzheimer's disease patients (n = 8, average age = 76 ± 5), non-Alzheimer's disease elderly (n = 6, average age = 65 ± 7), and young subjects (n = 8, average age = 28 ± 5). Every 5 minutes for 60 minutes, image of the eye's shape were taken, and the diameter of the pupils was measured.</li><li><strong>RESULTS</strong>: The results showed that differences in pupil dilation rate between Alzheimer's disease and non-Alzheimer's disease subjects were statistically significant. ROC analysis showed that after 35 minutes the sensitivity and specificity of the test were 100%.</li><li><strong>CONCLUSIONS</strong>: Based on our results, we concluded that this recording system might be an appropriate and reliable tool for pupil response diagnosis test of Alzheimer's disease.</li><li><strong>KEYWORDS</strong>: Alzheimer’s Disease, Tropicamide, Pupil.</li></ul&gt

Effect of crocus sativus on gentamicin induced nephrotoxicity

Crocus sativus, known as saffron, is used in folk medicine for treatment of different types of diseases, and its anti-inflammatory and free radical scavenging activities have been demonstrated. The present study evaluated gentamicin nephrotoxicity in saffron treated rats. Male Wistar rats (200-250g) were treated with saffron (40 or 80 mg/k/d) for 10 days, or saffron (40 or 80 mg/ kg/d) for 10 days and gentamicin 80 mg/kg/d for five days, starting from day 6. At the end of treatment, blood samples were taken for measurement of serum creatinine (SCr) and BUN. The left kidney was prepared for histological evaluation and the right kidney for Malondialdehyde (MDA) measurement. Gentamicin 80 (mg/k/d) increased SCr, BUN and renal tissue levels of MDA and induced severe histological changes. Saffron at 40 mg/k/d significantly reduced gentamicin-induced increases in BUN and histological scores (p<0.05). Gentamicin-induced increases in BUN, SCr and MDA and histological injury were significantly reduced by treatment with saffron 80 mg/k/d (p<0.05, p<0.001, p<0.05, and p<0.001 respectively). In conclusion, our results suggest that saffron treatment reduces gentamicin-induced nephrotoxicity and this effect seems to be dose dependent

Xanthomicrol Exerts Antiangiogenic and Antitumor Effects in a Mouse Melanoma (B16F10) Allograft Model

Xanthomicrol, a trimethoxylated hydroxyflavone, is the main active component of Dracocephalum kotschyi Boiss leaf extract. Preliminary in vitro studies identified this compound as a potential antiangiogenic and anticancer agent. This study aimed to evaluate in vivo anticancer effect of xanthomicrol and investigate its molecular mechanism of action in a mouse melanoma (B16F10) model. Effect of xanthomicrol on B16F10 melanoma cell viability was determined using the MTT assay. For in vivo experiments, C57BL/6 mice were inoculated subcutaneously with B16F10 cells. After five days, once daily administration of xanthomicrol, thalidomide, or vehicle was commenced and continued for 21 consecutive days. On the 26th day, blood samples and tumor biopsies were taken for subsequent molecular analysis. Xanthomicrol showed inhibitory effect on viability of B16F10 melanoma cells (IC50 value: 3.433 μg/ml). Initial tumor growth, tumor volume and weight, and angiogenesis were significantly decreased in xanthomicrol-treated animals compared with those in vehicle group. Protein expression of phosphorylated Akt, mRNA expressions of HIF-1α and VEGF in tumor tissues, and serum VEGF were significantly decreased in xanthomicrol-treated animals compared with vehicle-treated animals. Thus, xanthomicrol inhibited cancer cell growth both in vitro and in vivo. This effect, at least in part, was exerted by interfering with PI3K/Akt signaling pathway and inhibiting VEGF secretion by tumor cells. Further studies are required to elucidate the exact molecular mechanisms of antitumor activity of xanthomicrol

In vitro and in vivo activities of Peganum harmala extract against Leishmania major

Background: In vitro and in vivo antileishmanial activities of crude hydroalcoholic extract of peganum harmala seeds were investigated against Leishmania major. Methods: The extract of aerial parts of P harmala was obtained by maceration. The in vitro experiments were performed on promastigotes to assess antileishmanial activity of the extract using amphotericin B as a reference. The in vivo studies were carried out on cutaneous leishmaniasis in outbred mice to evaluate the effects of topical application of the ointment-based extract. Results: The in vitro experiments showed a concentration-dependent decrease of parasites number caused by the extract with an IC50 value of 59.4 μg/ml. In vivo studies demonstrated a significant post-treatment decrease in the lesion size and parasite count in infected animals, compared to placebo and control groups. High performance liquid chromatography (HPLC) of the crude extract demonstrated the existence of harmaline and harmine as beta-carboline alkaloids. Conclusions: P harmala seeds extract showed significant in vitro and in vivo antileishmanial activities. Most biological activity of the extract could be attributed to its beta-carboline content. However, another alkaloid of P harmala seeds extract, peganine, has also been reported to have antileishmanial activity. These beneficial effects can be attributed to the cumulative effects of various biologically active components present in it