Increased pressor function of central vasopressinergic system in hypertensive renin transgenic rats

OBJECTIVE: Renin transgenic hypertensive rats [TGR(mRen2)27] have increased contents of angiotensin II and arginine vasopressin (AVP) in the cardiovascular brain regions. The aim of the present study was to evaluate the effects of centrally released AVP on the regulation of baseline blood pressure in TGR(mRen2)27 rats and to determine the interaction between AVP and angiotensin II in the central control of blood pressure in this model of hypertension. DESIGN: Three basic series of experiments were performed on 20 TGR(mRen2)27 and 20 Hannover Sprague-Dawley conscious rats, chronically instrumented with lateral cerebral ventricle (LCV) cannulae and femoral artery catheters. In series 1, blood pressure and heart rate were recorded during an LCV infusion of artificial cerebrospinal fluid before and after LCV administration of angiotensin II. In series 2, the effects of an LCV administration of angiotensin 11 (100 ng) on mean arterial pressure and the heart rate were determined during LCV infusion of a selective AVP receptor (V1) antagonist [1-(1-mercapto-4-methylcyclohexaneacetic acid)-8-arginine vasopressin (MeCAAVP) and d(CH2)5[Tyr(Me)2,Ala-NH2(9)]AVP] or a selective angiotensin II type 1 (AT1) receptor antagonist (losartan) or both. In series 3, mean arterial pressure and the heart rate were determined after an LCV injection of either AVP (10 ng) or AVP together with angiotensin II. RESULTS: The LCV infusions of antagonists to V1 and AT1 receptors caused significant comparable decreases in baseline MAP in TGR(mRen2)27 but not in Sprague-Dawley rats. Angiotensin II elicited significant pressor responses, both in TGR(mRen2)27 and in Sprague-Dawley rats. Blockade of V1 receptors significantly reduced the duration and the maximum amplitude of the central pressor response to angiotensin II in TGR(mRen2)27 rats, whereas in Sprague-Dawley rats the maximum pressor effect was not significantly altered. In both strains, the pressor response to angiotensin II was abolished by blockade of AT1 receptors. CONCLUSIONS: The results indicate that the elevated blood pressure in TGR(mRen2)27 rats is partly caused by increased function of the brain angiotensinergic AT1 and vasopressinergic V1 systems. Centrally released AVP is involved in mediation of the pressor effect exerted by centrally applied angiotensin II in TGR(mRen2)27 rats.     

Giant cell tumor of lumbar vertebra. A case report with 13-year followup

A combined one stage anterior and posterior approach was used to excise a giant cell tumor involving the second lumbar vertebra. The tumor involved the anterior and posterior elements of the vertebra. A wide excision was feasible with immediate stabilization using the Luque instrumentation posteriorly and fibular strut grafts supporting the vertebral bodies anteriorly. The followup period was 13 years. There is no recurrence, and the patient has no symptoms of disease, and the fibular grafts are fully incorporated.     

Cloning and characterization of the nuclear gene and cDNAs for triosephosphate isomerase of the marine red alga Gracilaria verrucosa

cDNAs and an intronless single-copy nuclear gene (TPI1) encoding triosephosphate isomerase have been cloned and sequenced from the marine red alga Gracilaria verrucosa. The predicted amino-acid sequence of TPI1 is readily alignable with those of other known TPIs; 26 of 27 active-site residues and 19 of 26 intersubunit-contact residues are identical between TPIs of G. verrucosa and/or animals and green plants. A partial cDNA sequence of a second TPI gene (TPI2), presumably encoding plastid-localized TPI, was recovered by PCR and demonstrated by phylogenetic analysis to be red algal; no TP12 cDNA or genomic clones could be recovered. Genomic Southern analysis demonstrated that at least two TPI-like genes are present in the nuclear DNA of G. verrucosa.     

Relationship between mutagenic effects of drinking water and incidence of liver cancer in Fusui County--a prevalent area

Relationship between mutagenic activity of drinking water and incidence of liver cancer was studied in Fusui County with micronucleus technique in the root tips of vicia faba. Results showed there existed substance that caused chromosome aberration in the drinking pond water of Fusui County. Micronucleus effects on the root tips of vicia faba induced by the substance in different kinds of drinking water coincided with the incidence of liver cancer (r = 0.86, P < 0.05). It suggested the existence of these chemical mutants in the water may be one of the important factors that caused high incidence of liver cancer. It provided experimental evidence for the etiological theory of liver cancer caused by the pollution of drinking water.     

Decreased drug accumulation without increased drug efflux in a novel MRP-overexpressing multidrug-resistant cell line

KB/7D cells represent a multidrug-resistant subclone of human nasopharyngeal carcinoma KB cells generated by continuous exposure to the topoisomerase II inhibitor VP-16 (etoposide). KB/7D cells also show cross-resistance to doxorubicin and vincristine. Phenotypic traits of the cell line include a 2-fold decrease in topoisomerase II levels and a decrease in the uptake of VP-16 without an increase in the rate of drug efflux or expression of P-glycoprotein, suggesting a novel mechanism associated with the uptake of anticancer drugs. This study demonstrated that the multidrug-resistance associated protein (MRP) is overexpressed in KB/7D cells, and that the loss of resistance in revertant cells correlates with the loss of MRP. The resistance to VP-16 and doxorubicin could be overcome, partially, and resistance to vincristine could be overcome completely, by the L-enantiomer of verapamil, but not by the D-enantiomer or by BIBW 22 (4-[N-(2-hydroxy-2-methyl-propyl)-ethanolamino]-2,7-bis[cis-2,6-++ +dimethylmorpholino)-6-phenylpteridin), an inhibitor of MDR-1. L-Verapamil was shown to be significantly more potent than D-verapamil in modulating the accumulation defect in KB/7D cells towards doxorubicin, as measured by flow cytometry and confocal microscopy, and towards VP-16, as measured by increases in protein-linked DNA strand breaks. This suggests that KB/7D cells are multidrug resistant due to decreases in topoisomerase II levels and the overexpression of MRP, that MRP leads to a decrease in drug accumulation, and that L-verapamil can modulate the MRP-associated accumulation defect and drug-resistance phenotype. This contrasts with previous studies that suggest that MRP causes multidrug resistance by exporting cytotoxic drugs out of the cell and that did not show modulation of MRP by verapamil.     

Hybrid verrucous squamous cell carcinoma of sinonasal tract: a case report

Verrucous carcinoma is a variant of squamous cell carcinoma and should be distinguished from benign papilloma and well-differentiated nonverrucous squamous cell carcinoma. It is rare tumor of the sinonasal tract. Occasionally, conventional squamous cell carcinomatous components may be seen in verrucous carcinoma. This entity is called a hybrid verrucous squamous cell carcinoma. We report a case of hybrid verrucous squamous cell carcinoma occurring in the nasal cavity and paranasal sinus of a 67-year-old male. The removed mass shows the typical feature of verrucous carcinoma, but focally conventional squamous cell carcinomatous area is also noted. The treatment of this case follows verrucous carcinoma, but close follow up is mandatory because it may potentially spread to regional lymph nodes in contrast to pure form of verrucous carcinoma.     

Multi-criteria Decision-making Approach for Environmental Impact Assessment to Reduce the Adverse Effects Of Dams

Water Resources Management - Environmental Impact Assessments (EIAs) of development projects are necessary to minimize negative impacts and maximize benefits. The objective of this paper is to...     

Calcium carbonate and ammonium polyphosphate flame retardant additives formulated to protect ethylene vinyl acetate copolymer against fire: Hydrated or carbonated calcium?

In this study, the effect of the chemical nature of different calcium (Ca)-based minerals as flame retardant additives in combination with ammonium polyphosphate (APP), in 1:1 proportions, on the flame retardancy behavior and performance of ethylene vinyl acetate copolymer was discussed. Combining APP with partly and completely hydrated calcium oxide led to superior flame-retardant function detected in mass loss calorimeter measurements with respect to the corresponding system containing carbonated calcium. This privileged character was attributed to the higher reactivity of hydrated Ca-based fillers toward APP in comparison with Ca carbonate, which induced the formation of an intumescent residue. The difference between reactivity potential of hydrated and dry Ca was demonstrated by the newly formed thermally stable species, and further evidenced by thermogravimetric analysis performed on APP/fillers blends. Moreover, the presence of more crystalline domains in the Ca/phosphorus-based compounds was evidenced by XRD analysis of the mass loss calorimeter test residues. The results of this work highlight the role of blend additive systems on the performance of flame retardancy of polymer materials.     

Molecular Imaging and Preclinical Studies of Radiolabeled Long-Term RGD Peptides in U-87 MG Tumor-Bearing Mice

The Arg–Gly–Asp (RGD) peptide shows a high affinity for α_vβ₃ integrin, which is overexpressed in new tumor blood vessels and many types of tumor cells. The radiolabeled RGD peptide has been studied for cancer imaging and radionuclide therapy. We have developed a long-term tumor-targeting peptide DOTA-EB-cRGDfK, which combines a DOTA chelator, a truncated Evans blue dye (EB), a modified linker, and cRGDfK peptide. The aim of this study was to evaluate the potential of indium-111(¹¹¹In) radiolabeled DOTA-EB-cRGDfK in α_vβ₃ integrin-expressing tumors. The human glioblastoma cell line U-87 MG was used to determine the in vitro binding affinity of the radiolabeled peptide. The in vivo distribution of radiolabeled peptides in U-87 MG xenografts was investigated by biodistribution, nanoSPECT/CT, pharmacokinetic and excretion studies. The in vitro competition assay showed that ¹¹¹In-DOTA-EB-cRGDfK had a significant binding affinity to U-87 MG cancer cells (IC₅₀ = 71.7 nM). NanoSPECT/CT imaging showed ¹¹¹In-DOTA-EB-cRGDfK has higher tumor uptake than control peptides (¹¹¹In-DOTA-cRGDfK and ¹¹¹In-DOTA-EB), and there is still a clear signal until 72 h after injection. The biodistribution results showed significant tumor accumulation (27.1 ± 2.7% ID/g) and the tumor to non-tumor ratio was 22.85 at 24 h after injection. In addition, the pharmacokinetics results indicated that the ¹¹¹In-DOTA-EB-cRGDfK peptide has a long-term half-life (T_1/2λz = 77.3 h) and that the calculated absorbed dose was safe for humans. We demonstrated that radiolabeled DOTA-EB-cRGDfK may be a promising agent for glioblastoma tumor imaging and has the potential as a theranostic radiopharmaceutical.     

Production of propylene glycol fatty acid monoesters by lipase-catalyzed reactions in organic solvents

Fatty acid monoesters of propylene glycol (1,2-propanediol) are good water-in-oil emulsifiers. These esters were synthesized enzymatically to overcome the problems associated with chemical processes. APseudomonas lipase was added to reaction mixtures containing propylene glycol and various acyl donors (fatty acids, fatty acid ethyl esters, fatty acid anhydrides and triglycerides) in organic solvents, and the mixtures were shaken at 30°C. The products were analyzed by gas chromatography. The yield of monoesters was affected by the acyl donors, organic solvents, temperature, water content, pH memory and reaction time. The anhydrous (lyophilized) enzyme and fatty acid anhydrides were best for monoester production. The optimum pH ranges were 4–5 and 8–10. The yields of propylene glycol monolaurate, monomyristate, monopalmitate, monostearate and monooleate with 50 mM fatty acid anhydrides as acyl donors were 97.2, 79.6, 83.7, 89.7 and 93.4 mM, respectively; those with 50 mM fatty acids as acyl donors were 37.3, 28.7, 28.7, 35.3 and 36.2 mM, respectively. The yields of propylene glycol monopalmitate, monostearate and monooleate with 50 mM triglycerides as acyl donors were 87.4, 65.1 and 83.2 mM, respectively.