Reduction of the prenatal hypoxic-ischemic brain edema with noscapine

Cytotoxic free radicals and release of several neurotransmitters such as bradykinin contribute to the pathogenesis of hypoxic-ischemic brain damage. We have studied the efficacy of noscapine, an opium alkaloid and a bradykinin antagonist, in reducing post-hypoxic-ischemic damage in developing brain of 7-d-old rat pups. Hypoxic-ischemic injury to the right cerebral hemisphere was produced by legation of the right common carotid artery followed by 3 h of hypoxia with 8% oxygen. Thirty to 45 min before hypoxia the rat pups received noscapine (dose = 0.5-2 mg/kg) or saline. Pups were scarified at 24 h post recovery for the assessment of cerebral damage by histological methods. Our results showed that noscapine was an effective agent in reducing the extent of brain injury after hypoxic-ischemic insult to neonatal rats. Therefore, it is concluded that noscapine may be a useful drug in the managements of patients after stroke.     

NMR spectroscopy-based metabolomic study of serum in sulfur mustard exposed patients with lung disease

Sulfur mustard (SM) is a vesication chemical warfare agent for which there is currently no antidote. Despite years of research, there is no common consensus about the pathophysiological basis of chronic pulmonary disease caused by this chemical warfare agent. In this study, we combined chemometric techniques with nuclear magnetic resonance (NMR) spectroscopy to explore the metabolic profile of sera from SM-exposed patients. A total of 29 serum samples obtained from 17 SM-injured patients, and 12 healthy controls were analyzed by Random Forest. Increased concentrations of seven amino acids, glycerol, dimethylamine, ketone bodies, lactate, acetate, citrulline and creatine together with the decreased very low-density lipoproteins (VLDL) levels were observed in patients compared with control subjects. Our study reveals the metabolic profile of sera from SM-injured patients and indicates that NMR-based methods can distinguish these patients from healthy controls.     

Elimination of macro elements from inoculation and co-cultivation media enhances the efficiency of <Emphasis Type="Italic">Agrobacterium</Emphasis>-mediated transformation in <Emphasis Type="Italic">Petunia</Emphasis>

In order to evaluate the effect of inoculation and co-cultivation media elements on transformation frequency in Petunia hybrida, modified MS media with different elements were tested on Alvan and Large Flower Alvan (LF Alvan), two local cultivars. Leaf explants of both cultivars were inoculated with Agrobacterium tumefaciens strain LBA4404 (pBI121) containing neomycin phosphotransferase (nptII) and an intron-containing β-glucuronidase (gus) genes. When medium lacking KH₂PO₄, NH₄NO₃, KNO₃, and CaCl₂ was used as inoculation and co-cultivation medium, a higher frequency of transformation for Alvan (22%) and LF Alvan (16%) was obtained. Kanamycin resistant plantlets were stained blue by GUS assay. Furthermore, polymerase chain reaction (PCR) analysis revealed the presence of both gus and nptII genes in all putative transformants. Finally, southern blot hybridization confirmed insertion of 1–4 copies of gus gene in transgenic plants.     

Pulmonary hypertension and ascites as affected by dietary protein source in broiler chickens reared in cool temperature at high altitudes

As canola meal protein (CMP) has a lower arginine (Arg) content than soybean meal protein (SBMP), the main objective of this study was to investigate if replacing SBMP by CMP affected the incidence of pulmonary hypertension and ascites. Two hundred and seventy broiler chicks (Ross 308) were used to evaluate the effect of replacing CMP at proportionally 0, 0.5, and 1 for SBMP in a complete randomized block design, as mentioned in the Statistical analysis section (dietary treatments designated as CMP0, CMP0.5, and CMP1, respectively). The experiment was carried out on litter flooring from 6 to 42 days of age. The results indicate that broiler performance (body weight gain, feed intake, and feed conversion ratio) was significantly (P<0.05) impaired in the CMP1 group at 6–21 days but not at 21–42 days. Inclusion of canola meal (CM) in the diet significantly increased ascites and total mortality (P<0.05) and caused a decrease in the serum nitric oxide (NO) concentration with a concomitant increase (P<0.05) in the right ventricular weight ratio (RV/TV). Haematocrit, circulatory triiodothyronine and thyroxine thyroid hormone concentrations and serum alkaline phosphatase activity were unaffected by dietary treatments. In conclusion, the results of this study indicate that substitution of CMP for SBMP was associated with pulmonary hypertension (i.e., higher RV/TV) and ascites mortality in broiler chickens.     

Effect of Chemical Chaperones on Glucose-Induced Lysozyme Modifications

Nonenzymatic glycation of biomacromolecules occurs due to the diabetes mellitus and ageing. A number of small molecules, known as chemical chaperones, stabilize protein conformation against thermal and chemically induced denaturation. These compounds are including: polyamines (e.g. spermine and spermidine), amino acids (e.g. lysine) and polyols (e.g. glycerol). In this study the effect of spermidine (Spd), spermine (Spm), and glycerol on glycation, structure and function of lysozyme (LZ), as an extra-cellular protein, by different techniques is investigated. LZ is incubated with or without glucose (50 or 100 mM) in the absence or presence of Spd/Spm/glycerol at 37 °C up to 16 weeks. All the observed changes of glycated-LZ in comparison with the native protein, including: increased fluorescence emission, alteration in the secondary and tertiary structure, and reduced electrophoretic mobility- indicate its structural changes that are accompanied with its reduced activity. Glucose in the presence or absence of Spd induces the protein dimerization, but glucose plus Spm induces its trimmerization. In contrast, glycerol inhibits the LZ glycation and prevents the large changes on its structure and function. Glucose binds lysine residues, decreases the protein positive charges and induces some alterations in its structure and activity. Polyamines also directly bind to LZ, increase its positive charges and hence induce more glycation; more conformational changes, oligomerization and its inactivation in the presence of glucose, but glycerol affect the protein environment and preserve protein from these harmful effects.     

Feasibility study on the use of 230 MeV proton cyclotron in proton therapy centers as a spallation neutron source for BNCT

AimThe feasibility of using 230 MeV proton cyclotrons in proton therapy centers as a spallation neutron source for Boron Neutron Capture Therapy (BNCT) was investigated.BackgroundBNCT is based on the neutron irradiation of a ¹⁰B-containing compound located selectively in tumor cells. Among various types of neutron generators, the spallation neutron source is a unique way to generate high-energy and high-flux neutrons.Materials and MethodsNeutron beam was generated by a proton accelerator via spallation reactions and then the produced neutron beam was shaped to be appropriate for BNCT. The proposed Beam Shaping Assembly (BSA) consists of different moderators, a reflector, a collimator, as well as thermal and gamma filters. In addition, the simulated Snyder head phantom was utilized to evaluate the dose distribution in tumor and normal tissue due to the irradiation by the designed beam. MCNPX2.6 Monte Carlo code was used to optimize BSA as well as evaluate dose evaluation.ResultsA BSA was designed. With the BSA configuration and a beam current of 104 nA, epithermal neutron flux of 3.94 × 10⁶ [n/cm²] can be achieved, which is very low. Provided that we use the beam current of 5.75 μA, epithermal neutron flux of 2.18 × 10⁸ [n/cm²] can be obtained and the maximum dose of 38.2 Gy-eq can be delivered to tumor tissue at 1.4 cm from the phantom surface.ConclusionsResults for 230 MeV protons show that with proposed BSA, proton beam current about 5.75 μA is required for this purpose.     

Differential distribution of muscle and skin sympathetic nerve activity in patients with end-stage renal disease

End-stage renal disease (ESRD) is characterized by resting sympathetic overactivity. Baseline muscle sympathetic nerve activity (MSNA), which is governed by baroreflexes and chemoreflexes, is elevated in ESRD. Whether resting skin sympathetic nerve activity (SSNA), which is independent from baroreflex and chemoreflex control, is also elevated has never been reported in renal failure. The purpose of this study was to determine whether sympathetic overactivity of ESRD is generalized to include the skin distribution. We measured sympathetic nerve activity to both muscle and skin using microneurography in eight ESRD patients and eight controls. MSNA was significantly (P = 0.025) greater in ESRD (37.3 +/- 3.6 bursts/min) when compared with controls (23.1 +/- 4.4 bursts/min). However, SSNA was not elevated in ESRD (ESRD vs. controls, 17.6 +/- 2.2 vs. 16.1 +/- 1.7 bustst/min, P = 0.61). Similar results were obtained when MSNA was quantified as bursts per 100 heartbeats. We report the novel finding that although sympathetic activity directed to muscle is significantly elevated, activity directed to skin is not elevated in ESRD. The differential distribution of sympathetic outflow to the muscle vs. skin in ESRD is similar to the pattern seen in other disease states characterized by sympathetic overactivity such as heart failure and obesity.     

NMR- and GC/MS-based metabolomics of sulfur mustard exposed individuals: a pilot study

Sulfur mustard (SM) is a potent alkylating agent and its effects on cells and tissues are varied and complex. Due to limitations in the diagnostics of sulfur mustard exposed individuals (SMEIs) by noninvasive approaches, there is a great necessity to develop novel techniques and biomarkers for this condition. We present here the first nuclear magnetic resonance (NMR) and gas chromatography-mass spectrometry (GC/MS) metabolic profiling of serum from and healthy controls to identify novel biomarkers in blood serum for better diagnostics. Of note, SMEIs were exposed to SM 30 years ago and that differences between two groups could still be found. Pathways in which differences between SMEIs and healthy controls are observed are related to lipid metabolism, ketogenesis, tricarboxylic acid (TCA) cycle and amino acid metabolism.     

Synthesis and crystal structures of dimeric W(Mo)/Cu/S and polymeric W/Cu/S neutral clusters with flexible 1,4-bis(3,5-dimethylpyrazol-1-yl)butane as a linker ligand

Reactions of [MES₃]²⁻ (M = W, Mo; E = S, O) with CuCl and bbd [1,4-bis(3,5-dimethylpyrazol-1-yl)butane] in DMF affords two new double nest-shape clusters, [WOS₃Cu₃Cl(μ-bbd)]₂ (1) and [MoOS₃Cu₃Cl(μ-bbd)]₂ (2) and a novel one-dimensional polymeric complex [WS₄Cu₂(μ-bbd)]_n (4). The complexes have been characterized by elemental analysis, IR and UV-Vis spectroscopy, and single-crystal X-ray diffraction. In the core structure of the isostructural dimeric [MOS₃Cu₃Cl(μ-bbd)]₂ clusters, the copper atoms have a distorted trigonal planar geometry, with CuS₂N and CuS₂Cl core environments. The [MOS₃Cu₃] fragments are interconnected by a pair of flexible μ-bbd ligands via their nitrogen donor atoms to form a centrosymmetric macrocyclic twin-nest-shaped cluster in which the two fragments are also linked by direct secondary Cu…Cl interactions. Complex 4 represents the first example of a polymeric heterothiometallic cluster, interconnected by bbd ligands, to be structurally characterized by X-ray crystallography. In the repeat unit of 4, the skeleton of the cluster core [CuS₂WS₂Cu] has an essentially linear Cu…W…Cu arrangement. The W atom retains the tetrahedral geometry of the parent [WS₄]²⁻ anion. These cluster cores are linked by bbd bridges having alternately two different conformations to construct a zigzag structure. Complexes [MoS₄Cu₃Cl(bbd)_0.5]₂ (3) and [WS₄Cu₄(NCS)₂(bbd)₂]_n (5) have been synthesized and characterized by elemental analysis, IR and UV-Vis spectroscopy, but we have been unable to grow suitable crystals of 3 and 5 for X-ray analysis.