Factors affecting spore germination in Aspergillus niger

Temperature markedly affected germination and germ tube length of A. niger. More than 90% of the spores were germinated in the range 30°–34 °C and formed maximum length of germ tubes. At temperatures from 38° to 43 °C, the proportion of the spores that germinated as well as the germ tube length were both gradually decreased. However, at 47°C germ tube formation was completely inhibited up to 15 hrs. after inoculation.High relative humidity was found necessary for the spore germination of A. niger. Germination failed to occur at 76% relative humidity. At 78 and 81% relative humidity germination was detected 15 hrs. after inoculation while at the higher humidities germination was started after 6 hrs. only.Conidiospores of A. niger were very sensitive to changes in the hydrogen ion concentration, pH. Complete inhibition of germination was found at pH less than 3.5. The germination and the length of the formed germ tubes increased with pH to reach their maximum rates at pH 4.5.     

Enhancement of Dissolution and Skin Permeability of Pentazocine by Proniosomes and Niosomal Gel

Proniosomes (PN) are the dry water-soluble carrier systems that may enhance the oral bioavailability, stability, and topical permeability of therapeutic agents. The low solubility and low oral bioavailability due to extensive first pass metabolism make Pentazocine as an ideal candidate for oral and topical sustained release delivery. The present study was aimed to formulate the PNs by quick slurry method that are converted to niosomes (liquid dispersion) by hydration, and subsequently formulated to semisolid niosomal gel. The PNs were found in spherical shape in the SEM and stable in the physicochemical and thermal analysis (FTIR, TGA, and XRD). The quick slurry method produced high recovery (>?80% yield) and better flow properties (θ?=?28.1–37.4°). After hydration, the niosomes exhibited desirable entrapment efficiency (44.45–76.23%), size (4.98–21.3 μm), and zeta potential (??9.81 to ??21.53 mV). The in vitro drug release (T_100%) was extended to more than three half-lives (2–4 h) and showed good fit to Fickian diffusion indicated by Korsmeyer-Peppas model (n?=?0.136–0.365 and R²?=?0.9747–0.9954). The permeation of niosomal gel was significantly enhanced across rabbit skin compared to the pure drug-derived gel. Therefore, the PNs are found promising candidates for oral as dissolution enhancement and sustained release for oral and topical delivery of pentazocine for the management of cancer pain.     

Dry Gel Containing Optimized Felodipine-Loaded Transferosomes: a Promising Transdermal Delivery System to Enhance Drug Bioavailability

Felodipine has a very low bioavailability due to first-pass metabolism. The aim of this study was to enhance its bioavailability by transdermal application. Felodipine-loaded transferosomes were prepared by thin-film hydration using different formulation variables. An optimized formula was designed using statistical experimental design. The independent variables were the used edge activator, its molar ratio to phosphatidylcholine, and presence or absence of cholesterol. The responses were entrapment efficiency of transferosomes, their size, polydispersity index, zeta potential, and percent drug released after 8 h. The optimized formula was subjected to differential scanning calorimetry studies and its stability on storage at 4°C for 6 months was estimated. This formula was improved by incorporation of different permeation enhancers where ex vivo drug flux through mice skin was estimated and the best improved formula was formulated in a gel and lyophilized. The prepared gel was subjected to in vivo study using Plendil® tablets as a reference. According to the calculated desirability, the optimized transferosome formula was that containing sodium deoxycholate as edge activator at 5:1 M ratio to phosphatidylcholine and no cholesterol. The thermograms of this formula indicated the incorporation of felodipine inside the prepared vesicles. None of the tested parameters differed significantly on storage. The lyophilized gel of labrasol-containing formula was chosen for in vivo study. The relative bioavailability of felodipine from the designed gel was 1.7. In conclusion, topically applied lyophilized gel containing felodipine-loaded transferosomes is a promising transdermal delivery system to enhance its bioavailability.     

Introducing novel potent anticancer agents of 1H-benzo[f]chromene scaffolds,targeting c-Src kinase enzyme with MDA-MB-231 cell line anti-invasion effect

In our effort to develop novel and powerful agents with anti-proliferative activity, two new series of 1H-benzo[f]chromene derivatives, 4a–h and 6a–h, were synthesised using heterocyclocondensation methodologies under microwave irradiation condition. The structures of the target compounds were established on the basis of their spectral data, IR, ¹H NMR, ¹³?C NMR, ¹³?C NMR-DEPT/APT, and MS data. The new compounds have been examined for their anti-proliferative activity against three cancer cell lines, MCF-7, HCT-116, and HepG-2. Vinblastine and Doxorubicin have been used as positive controls in the viability assay. The obtained results confirmed that most of the tested molecules revealed strong and selective cytotoxic activity against the three cancer cell lines. Moreover, these molecules exhibited weak cytotoxicity on the HFL-1?line, which suggested that they might be ideal anticancer candidates. The SAR study of the new benzochromene compounds verified that the substituents on the phenyl ring of 1H-benzo[f]chromene nucleus, accompanied with the presence of bromine atom or methoxy group at the 8-position, increases the ability of these molecules against the different cell lines. Due to their high anti-proliferative activity, compounds 4c and 6e were selected to be examined their proficiency to inhibit the invasiveness of the highly sensitive and invasive breast cancer cell line, MDA-MB-231. The anti-invasion behaviour of these molecules against the highly sensitive, non-oestrogen, and progesterone MDA-MB-231 cell line gave rise to their decreasing metastatic effect compared to the reference drug. Furthermore, this report explores the apoptotic mechanistic pathway of the cytotoxicity of the target compounds and reveals that most of these compounds enhance the Caspase 3/7 activity that could be considered as potential anticancer agents.     

FPS-ZM1 and valsartan combination protects better against glomerular filtration barrier damage in streptozotocin-induced diabetic rats

Despite the effectiveness of renin-angiotensin blockade in retarding diabetic nephropathy progression, a considerable number of patients still develop end-stage renal disease. The present investigation aims to evaluate the protective potential of FPS-ZM1, a selective inhibitor of receptor for advanced glycation end products (RAGE), alone and in combination with valsartan, an angiotensin receptor blocker, against glomerular injury parameters in streptozotocin-induced diabetic rats. FPS-ZM1 at 1 mg/kg (i.p.), valsartan at 100 mg/kg (p.o.), and their combination were administered for 4 weeks, starting 2 months after diabetes induction in rats. Tests for kidney function, glomerular filtration barrier, and podocyte slit diaphragm integrities were performed. Combined FPS-ZM1/valsartan attenuated diabetes-induced elevations in renal levels of RAGE and phosphorylated NF-κB p65 subunit. It ameliorated glomerular injury due to diabetes by increasing glomerular nephrin and synaptopodin expressions, mitigating renal integrin-linked kinase (ILK) levels, and lowering urinary albumin, collagen type IV, and podocin excretions. FPS-ZM1 also improved renal function as demonstrated by decreasing levels of serum cystatin C. Additionally, the combination also alleviated indices of renal inflammation as revealed by decreased renal monocyte chemoattractant protein 1 (MCP-1) and chemokine (C-X-C motif) ligand 12 (CXCL12) expressions, F4/80-positive macrophages, glomerular TUNEL-positive cells, and urinary alpha-1-acid glycoprotein (AGP) levels. These findings underline the benefits of FPS-ZM1 added to valsartan in alleviating renal glomerular injury evoked by diabetes in streptozotocin rats and suggest FPS-ZM1 as a new potential adjunct to the conventional renin-angiotensin blockade.     

Molecular testing of <Emphasis Type="Italic">Klebsiella pneumoniae</Emphasis> contaminating tissue allografts recovered from deceased donors

Microbiological screening of tissue allografts is crucial to prevent the transmission of bacterial and fungal infections to transplant recipients. Klebsiella was the most prevalent and resistant contaminating microorganism observed in our setting in the Iranian Tissue Bank. This study was conducted to determine the presence of extended-spectrum β-lactamase (ESBL) genes, antimicrobial resistance patterns of Klebsiella pneumoniae isolates, and their clonal relationships in allograft materials. K. pneumoniae contaminating bone and other tissue allografts recovered from deceased donors were identified and ESBL isolates were detected using a phenotypic confirmatory method. Antimicrobial susceptibility testing was carried out using the disk diffusion method. Distribution of ESBL genes and molecular typing were performed using polymerase chain reaction (PCR) and Repetitive-element (rep-PCR) methods. Of 3828 donated tissues, 51 (1.3%) were found contaminated by K. pneumoniae isolates. Compared to tissue allografts from brain-dead, heart-beating tissue donors, allografts from donors with circulatory cessation were associated with a higher risk of K. pneumoniae contamination [odds ratio (OR), 1.2 (CI 95% 0.9–2.3) (P value < 0.001)]. Half of the isolates produced ESBL, and the rate of susceptibility to cephalosporins was 51%. Among isolates, 22 (43.1%) harbored CTX-M, 31 (60.8%) SHV, and 9 (17.6%) harbored TEM types. The rep-dendrogram indicated that clones having identical or related strains with a similar antibiotype were isolated in the same period. This study provides evidence that a single clone of K. pneumoniae contaminated tissue allografts recovered from many different donors. A single clone found on tissues from several donors suggests contamination of tissues from a single source such as the tissue recovery process and environment. Genomic DNA testing and clonality of contaminating bacteria using molecular methods can focus the epidemiologic investigation on the tissue allograft recovery process including a search for contamination of the tissue recovery room environment, recovery staff, recovery equipment, reagents, solutions and supplies.     

NTproBNP and ST2 as predictors for all-cause and cardiovascular mortality in elderly patients with symptoms suggestive for heart failure

Background: A new biomarker, suppression of tumorigenicity 2 (ST2) has been introduced as a marker for fibrosis and hypertrophy. Its clinical value in comparison with N-terminal pro-hormone of brain natriuretic peptide /Amino-terminal pro-B-type natriuretic peptide (NTproBNP) in predicting mortality in elderly patients with symptoms of heart failure (HF) is still unclear.

Aim: To evaluate the prognostic value for all-cause- and cardiovascular mortality of ST2 or NTproBNP and the combination of these biomarkers.

Patients and methods: One hundred seventy patients patients with clinical symptoms of HF (77 (45%) were with verified HF) were recruited from one selected primary health care center (PHC) in Sweden and echocardiography was performed in all patients. Blood samples were obtained from 159 patients and stored frozen at –70?°C. NTproBNP was analyzed at a central core laboratory using a clinically available immunoassay.ST2 was analyzed with Critical Diagnostics Presage ST2 ELISA immunoassay.

Results: We studied 159 patients (mean age 77?±?8.3?years, 70% women). During ten years of follow up 78 patients had died, out of which 50 deaths were for cardiovascular reasons. Continuous NTproBNP and ST2 were both significantly associated with all-cause mortality (1.0001; 1.00001–1.0002, p?=?0.04 and 1.03; 1.003–1.06, p?=?0.03), NTproBNP but not ST2 remained significant for cardiovascular mortality after adjustments (1.0001; 1.00001–1.0002, p?=?0.03 and 1.01; 0.77–1.06, p?=?0.53), respectively. NTproBNP above median (>328?ng/L) compared to below median was significantly associated with all-cause mortality(HR: 4.0; CI :2.46–6.61; p?p?Conclusion: In elderly patients with symptoms of heart failure ST2 was not superior to NTproBNP to predict all cause or cardiovascular mortality. Furthermore, it is unclear if the combination of ST2 and NTproBNP will improve long-term prognostication beyond what is achieved by NTproBNP alone.     

Bioaccumulation and rhizofiltration potential of Pistia stratiotes L. for mitigating water pollution in the Egyptian wetlands

The bioaccumulation and rhizofiltration potential of P. stratiotes for heavy metals were investigated to mitigate water pollution in the Egyptian wetlands. Plant and water samples were collected monthly through nine quadrats equally distributed along three sites at Al-Sero drain in Giza Province. The annual mean of the shoot biomass was 10 times that of the root. The concentrations of shoot heavy metals fell in the order: Fe < Mn < Cr < Pb < Cu < Zn < Ni < Co < Cd, while that of the roots were: Fe < Mn < Cr < Pb < Zn < Ni < Co < Cu < Cd. The bio-concentration factor (BCF) of most investigated heavy metals, except Cr and Pb, was greater than 1000, while the translocation factor (TF) of most investigated metals, except Pb and Cu, did not exceed one. The rhizofiltration potential (RP) of heavy metals was higher than 1000 for Fe, and 100 for Cr, Pb and Cu. Significant positive correlations between Fe and Cu in water with those in plant roots and leaves, respectively were recorded, which, in addition to the high BCF and RP, indicate the potential use of P. stratiotes in mitigating these toxic metals.     

A novel spectrofluorimetric method for determination of imatinib in pure,pharmaceutical preparation,human plasma,and human urine

The following paper represents a simple, highly sensitive, responsive validated and developed spectrofluorimetric method for estimation of imatinib (IMB) in its pure, commercial preparation, human urine and human blood plasma. The calibration curve was in the range 4–900 ng ml^?1 for pure form and urine and 8–900 ng ml^?1 for plasma in a medium contains carboxymethyl cellulose (CMC) and acetate buffer (pH 5) with excitation wavelength (λ_ex) 230 nm and emission wavelength (λ_em) 307 nm. The limit of detection (LOD) was 0.37 ng ml^?1 for the pure form, 0.64 ng ml^?1 for human urine, and 0.70 ng ml^?1 for human plasma, while the limit of quantitation (LOQ) was 1.2 for pure form, 1.91 for urine and 2.1 for plasma. The suggested method was successfully applied for evaluation of IMB in tablets within 99% mean percentage recovery. The excipients that are usually used as additives in pharmaceutical dosage form did not interfere with the suggested method. The method was efficiently used for estimation of IMB in human urine and human plasma. The effect of some cations that might be present in urine and plasma was also studied. The method was also focused on human volunteers and in vitro drug release.     

Human health risks from consuming cabbage (Brassica oleracea L. var. capitata) grown on wastewater irrigated soil

The present study investigated the impact of cumulative irrigation with wastewater on the soil properties and, its health hazards on the consumers of cabbage plants at south Cairo Province, Egypt. Irrigation water, soil and cabbage plants were sample d from two polluted and other two unpolluted farms. The physicochemical properties of water and soil were analyzed and the growth parameters, as well as nutrients and heavy metals concentration in cabbage were investigated. In addition, the daily intake of metals (DIM) and health risk index (HRI) were estimated. Wastewater posed a decrease in the availability of N, P and K, but increases heavy metals in the soil solution. Cabbage stem and root lengths as well as the number of leaves and biomass were greatly reduced in the polluted farms. In addition, the photosynthetic pigments, carbohydrates and proteins were decreased under pollution stress. The concentration of most investigated metals in the leaves and roots were increased with translocation factor greater than one for Pb, Cd, As, Cr, Ni, Fe, and Co. The study revealed that the HRI exceeded one for Pb and Cd in polluted and unpolluted plants; and Fe in polluted ones. Irrigation with wastewater is not suitable for cabbage as it has health risks on humans due to accumulation of heavy metals. It worth noting that, the high ability of cabbage plants to accumulate Pb and Cd from both polluted and unpolluted soils should be taken into consideration when consuming this plant.