Influence of heat transfer and wetting angle on condensable fluid flow through nanoporous anodic alumina membranes.

The flow of isobutane and of freon 142b (1-chloro-1,1-difluoro-ethane) through anodic alumina membranes with pore diameters between 18 and 60 nm in a capillary condensation regime is experimentally and theoretically explored. The capillary condensation effect increases the membrane permeance for condensable gases from 25 to 150 m3(STP) m-2 bar-1 h-1 at certain conditions. To describe the experimental results, a model is suggested accounting for heat transfer from the condensing to the evaporating meniscus, different boundary conditions for the heat transfer between the environment and the membrane, and wettability of the pore wall. The proposed model indicates a large influence of heat supply from the environment to the membrane on the permeance in the capillary condensation regime and a moderate influence of condensate contact angle in the range of 0-60°. Measuring the temperature of the permeate side of the membrane allows to find a suitable boundary condition to describe heat transfer. The obtained boundary condition yields an excellent fit of experimental results of condensate flow through membranes with different pore diameters for the two utilized fluids. Also, confocal Raman spectroscopy gave evidence on the fraction of pores filled with condensate.

Synthesis and Biological Evaluation of Chalconesulfonamides: En Route to Proapoptotic Agents with Antiestrogenic Potency.

Breast and other estrogen receptor α-positive cancers tend to develop resistance to existing drugs. Chalcone derivatives possess anticancer activity based on their ability to form covalent bonds with targets acting as Michael acceptors. This study aimed to evaluate the anticancer properties of a series of chalcones (7a-l) with a sulfonamide group attached to the vinyl ketone moiety. Chalconesulfonamides showed a potent antiproliferative effect at low micromolar concentrations against several cancer cell lines, including ERα-positive 4-hydroxytamoxifen-resistant MCF7/HT2. Immunoblotting of samples treated with the lead compound 7e revealed its potent antiestrogenic activity (ERα/GREB1 axis) and induction of PARP cleavage (an apoptosis marker) in breast cancer cells. The obtained compounds represent a promising basis for further development of targeted drugs blocking hormone pathways in cancer cells.

Indoline-5-Sulfonamides: A Role of the Core in Inhibition of Cancer-Related Carbonic Anhydrases, Antiproliferative Activity and Circumventing of Multidrug Resistance.

The overexpression and activity of carbonic anhydrase (CA, EC 4.2.1.1) isoforms CA IX and CA XII promote the accumulation of exceeding protons and acidosis in the extracellular tumor environment. Sulfonamides are effective inhibitors of most families of CAs. In this study, using scaffold-hopping, indoline-5-sulfonamide analogs 4a-u of the CA IX-selective inhibitor 3 were designed and synthesized to evaluate their biological properties. 1-Acylated indoline-5-sulfonamides demonstrated inhibitory activity against tumor-associated CA IX and XII with KI values up to 132.8 nM and 41.3 nM. Compound 4f, as one of the most potent inhibitors of CA IX and XII, exhibits hypoxic selectivity, suppressing the growth of MCF7 cells at 12.9 µM, and causes partial inhibition of hypoxia-induced CA IX expression in A431 skin cancer cells. 4e and 4f reverse chemoresistance to doxorubicin of K562/4 with overexpression of P-gp.

Synthesis, biological evaluation, and in silico studies of potential activators of apoptosis and carbonic anhydrase inhibitors on isatin-5-sulfonamide scaffold.

Carbonic anhydrase IX is a promising target for the search for new antitumor compounds with improved properties. Using the molecular hybridization approach, on the basis of structures of a selective carbonic anhydrase IX inhibitor 3 and an activator of apoptosis 2 (1), a series of 1-substituted isatin-5-sulfonamides 5a-5u were designed and synthesized. The study of the inhibitory activity of isatin-5-sulfonamides showed the ability to inhibit I, II, IX, XII isoforms at nano- and micromolar concentrations. Docking of compounds 5e and 5k into the active site of II and IX carbonic anhydrase isoforms showed the coordination of sulfonamidate anions with zinc cations, as well as a number of additional hydrophobic interactions. The trifluoromethylthio derivative 5r suppressed the growth of tumor cells at low micromolar concentrations, maintaining activity on resistant lines and under hypoxic conditions. Immunoblotting of MCF7 cells treated with the 5r revealed its antiestrogenic activity and ability to activate apoptosis in tumor cells.

Mass flow and momentum flux in nanoporous membranes in the transitional flow region.

An experimental study of momentum transfer in nanoporous polymeric track-etched membranes with pore diameters ranging from 100 to 1300 nm and nanochannel lengths of 12-20 µm was performed using He, N2, CO2, and SF6 propellants in a wide range of plenum and background pressures. Mass flux through the membranes was elaborated as a combination of Knudsen diffusion and viscous flow at Knudsen numbers above 0.1 and become choked at lower Knudsen numbers. The discharge coefficient for the membranes attained was 0.6, making the permeation rate similar to that of thin orifices. The effect is attributed to the mirror reflection of the molecules from the pore walls at low angles of incidence. The exhaust gas velocity is found to be dependent on the plenum to background pressure ratio and channel length-to-diameter ratio, reaching 0.9 of the velocity of the gas expanded to vacuum (up to 2 M). Close to an isothermal expansion occurs in nanochannels of all sizes. A general quantitative description for gas expansion in nanochannels is provided. The highest thrust is generated in the choked flow regime with the SF6 propellant and a value of 4.5 N cm-2 is attained at a propellant consumption of 0.165 kg (cm2 s)-1 for the membranes with 1300 nm nanochannels. The specific impulse of 138 s is reached for helium. The results show the prospects of the utilization of nanoporous membranes in cold gas propulsion systems.

Anodic alumina membrane capacitive sensors for detection of vapors.

Here we report membrane capacitive sensors based on anodic aluminum oxide (AAO) Au/AAO/Au structures fabricated by aluminum anodization, followed by gold electrodes sputtering on the countersides of porous ceramic membrane. Electrochemical impedance spectroscopy with AC amplitude 5-100 mV in the frequency range of 1-1000 Hz was utilized for sensor characterization in the presence of water and organic vapors in a full range of P/P0. The sensors illustrate ultimate sensitivity to ambient environment with exponential-scale capacitance relation to vapors content resulting in typical 4-6 orders of magnitude response signal change for 15-85% P/P0 range at a single AC frequency, and up to 7 orders of magnitude response range for 0-100% P/P0 pressure range with using two different AC frequencies. In case of water vapors, the sensitivity increases from ~0.5 nF/RH% at ~20 RH% to over ~1.0 µF/RH% at ~80 RH%. The sensors are capable for highly accurate sensing of gas humidity as well as any dissociative vapors with pKa <30. They are also sensible to polar components with high enough dipole moment or polarizability. The capacitance is affected by any adsorbed molecules, including those having zero dipole moment. The data for sensor response to CH3OH, C2H5OH, CH2ClCHF2, i-C4H10 depending on partial pressures is provided. Due to high porosity (10-30%) and gaseous permeance (up to 200 m3(STP) m-2 bar-1 h-1) the sensors offer fast response rate and a possibility for flow-through measurements, providing also a mass-flow response option, which was tested with SF6, CO2, N2 and He. The basic principles of dielectric loss sensor and the equivalent scheme were proposed for sensor operation in different environment, allowing estimating sensor response.

Pot, atom and step economic (PASE) assembly of salicylaldehydes, malononitrile dimer and 4-hydroxypyridine-2(1H)-ones into medicinally relevant 5H-chromeno[2,3-b]pyridine scaffold.

The new multicomponent reaction (MCR) has been found: one-pot selective and efficient formation of the new 5-(4-hydroxy-2-oxo-1,2-dihydropyridin-3-yl)-substituted 5H-chromeno[2,3-b]pyridines in 61-97% yields directly from simple and easily available salicylaldehydes, malononitrile dimer and 4-hydroxypyridine-2(1H)-ones in small amount of pyridine-ethanol catalyst/solvent system. This complex "domino" transformation includes Knoevenagel condensation of salicylaldehyde with malononitrile dimer, Michael addition of 4-hydroxypyridine-2(1H)-one, double Pinner-type reaction cyclization and isomerization with following protonation. This facile multicomponent process opens a new way to 5-(4-hydroxy-2-oxo-1,2-dihydropyridin-3-yl)-substituted 5H-chromeno[2,3-b]pyridine systems, which are promising compounds for the treatment for human inflammatory TNFα-mediated diseases and different biomedical applications.

Time-resolved measurement of surface diffusion induced by femtosecond laser pulses.

Diffusion of atomic oxygen on a vicinal Pt111 surface induced by femtosecond laser pulses has been studied using optical second-harmonic generation as a sensitive in situ probe of the step coverage. Time-resolved studies of the hopping rate for step-terrace diffusion with a two-pulse correlation scheme reveal a time constant of 1.5 ps for the energy transfer from the electronic excitation of the substrate to the frustrated translations of the adsorbate.

Cancer-related patient education: an overview of the last decade of evaluation and research.

PURPOSE/OBJECTIVES: To provide an overview of cancer-related patient-education research to determine future research needs. DATA SOURCES: A literature search of peer-reviewed articles from 1989-1999. Databases that were searched included Medline, CINAHL, HealthStar, ERIC, CancerLit, and PubMed. DATA SYNTHESIS: 176 articles were analyzed and synthesized into narrative form. CONCLUSIONS: Patients with cancer want and benefit from information, especially when making treatment decisions. Education helps patients manage side effects and improves adherence. Literacy is an important factor in materials development. The efficacy of computer-assisted learning, audio and video programs, and telephone interventions is supported in a variety of patient groups. Pain education can improve pain control, but the impact on fatigue has not been well researched. IMPLICATIONS FOR NURSING PRACTICE: Patient education is an important component of nursing care. Research has confirmed its impact in many areas but questions still remain.

Diagnostic problems in nodular regenerative hyperplasia (nodular transformation) of the liver. Review of the literature and report of two cases.

Nodular regenerative hyperplasia (NRH) is a rare lesion of the liver associated with portal hypertension in more than half of patients. We present two cases demonstrating complications and diagnostic problems of NRH and review the pathogenesis, clinical, radiologic, and pathologic features of 240 cases in the literature. Patient 1 died from variceal bleeding as a complication of NRH. Patient 2 presented with ascites. Sonographic, computed-tomographic and magnetic resonance findings did not differ from liver cirrhosis. Three needle biopsies showed nonspecific reactive hepatitis. Wedge liver biopsy provided the correct diagnosis of NRH and a shunt operation was performed. Non-Hodgkin's lymphoma (centroblastic type) was diagnosed three years after NRH. At present there is no clinical or radiologic evidence of progression of NRH in this patient. The diagnosis of NRH cannot be made without histologic examination. Correct diagnosis is difficult in percutaneous needle biopsy. Therefore, laparoscopically guided liver biopsy or wedge biopsy is often necessary for diagnosis. NRH should be included in the differential diagnosis of portal hypertension. Portal diversion can be considered.

Comparative carcinogenicity of N-nitrosobis(2-oxopropyl)-amine and N-nitrosomethyl(2-oxopropyl)amine following subcutaneous or oral administration to rats.

The carcinogenicity of N-nitrosomethyl(2-oxopropyl)amine (MOP), a postulated proximate carcinogen of N-nitrosobis(2-oxopropyl)-amine (BOP), was tested after either a single subcutaneous (s.c.) injection or weekly intragastric (i.g.) administration in Wistar-derived MRC rats and was compared with the effect of BOP, given similarly and at equitoxic doses. Following i.g. administration, MOP induced a high incidence of neoplasms in the pharynx and esophagus which, however, were not affected by BOP; on the other hand, tumors of the thyroid, lungs, colon and urethra occurred in a greater incidence following BOP than after MOP, and renal neoplasms were found only following MOP, given s.c. Moreover, there were remarkable sex differences in the responses of the rats' respiratory and urothelial tissues to these two carcinogens: nasal cavity carcinomas, pulmonary adenomas, urinary and urethra papillomas were induced primarily or exclusively in male rats treated with BOP, either s.c. or i.g., whereas such sex differences were not found following either route of MOP administration. There were also differences in the spectrum of the neoplasms induced by BOP or MOP depending upon the route of their administration. For example, MOP was more effective in inducing nasal, esophageal and hepatic tumors when given orally, compared to its effect following the s.c. route, and thyroid and renal tumors were induced only after its s.c. injection. The results point to a complexity of nitrosamine carcinogenesis and also indicate that in some tissues activation of BOP, but not of MOP, depends on sex hormones.

The role of testosterone in the nasal cavity tumors induced by N-nitrosobis(2-oxopropyl)amine in rats.

In a previous study in rats we have shown that castration prior to weekly administration of N-nitrosobis(2-oxopropyl)amine (BOP) prevents induction of nasal and paranasal cavity (NPNC) tumors, indicating androgen dependency of these neoplasms. To investigate the possible inhibitory effect of testosterone withdrawal on the growth of NPNC tumors, in the present study rats were castrated following weekly treatment with BOP for 10, 20 or 30 weeks. This treatment did not alter the incidence, type, location, latency or multiplicity of NPNC tumors. However, simultaneous treatment of castrated rats with BOP and testosterone (T) yielded NPNC tumors in an incidence and patterns comparable to that seen in BOP-treated intact and BOP-plus-T-treated intact rats. Serological examination revealed abnormally high levels of T and 17-beta estradiol (E) in rats, which were killed immediately after 10, 20 or 30 weekly BOP administrations. The overall results suggest that the initiation but not the promotional stage of NPNC carcinogenesis is governed by androgens.

Effect of cholecystokinin on pancreatic carcinogenesis in the hamster model.

To examine the effect of cholecystokinin (CCK) on pancreatic carcinogenicity in the hamster model, two sets of experiments were carried out. In one study, CCK (20 IDU/kg body wt) was given 3 h before, simultaneously with or 3 h after a single dose (20 mg/kg body wt) of N-nitrosobis(2-oxopropyl)amine (BOP). In another experiment, hamsters were treated similarly except that both CCK (20 IDU/kg body wt) and BOP (2.5 mg/kg body wt) were given weekly for 20 weeks. The results showed that CCK in the first experiment (single BOP dose) inhibited pancreatic cancer induction in a statistically significant fashion when given either 3 h prior to (P less than 0.05) or simultaneously with BOP (P less than 0.0005); however, CCK, when administered after BOP did not alter the cancer incidence as compared with hamsters treated with BOP alone. In the second experiment (chronic BOP treatment) the pattern and the incidence of pancreatic tumors were not affected by CCK.

Induction of prostatic carcinomas and lower urinary tract neoplasms by combined treatment of intact and castrated rats with testosterone propionate and N-nitrosobis(2-oxopropyl)amine.

The effect of exogenous testosterone on prostatic carcinogenicity of N-nitrosobis(2-oxopropyl)amine (BOP) in intact and castrated rats was examined in Wistar-derived MRC rats. Daily administration of BOP (either s.c. or i.g.) for 3 days, at a dose of 20 mg/kg b.w. at the heights of prostatic cell proliferation induced by testosterone, led to development of a large number of prostatic tumors, the incidence of which, however, was dependent on the duration of testosterone administration. Testosterone given for life following BOP administration induced prostatic cancer in over 60% of rats, regardless of whether BOP was given orally or s.c., or whether the rats were orchiectomized or not, whereas tumor incidence was significantly lower in rats treated with testosterone for only a short period of time. One (3%) orchiectomized rat, which received testosterone only during BOP treatment, and four (15%) of rats treated with testosterone only for life also developed carcinomas. Histologically, a large number of BOP + testosterone-induced prostatic tumors were adenocarcinomas of various histological patterns and arose primarily from the dorsal lobe, whereas the great majority of squamous cell carcinomas were found in the ventral lobe. Simultaneously induced tumors were papillomas and carcinomas of the urinary bladder and urethra. Testosterone appeared to enhance the incidence of urinary bladder tumors, but not of the urethral tumors, whereas orchiectomy inhibited urethral carcinogenesis, and, to much lesser extent, urinary bladder tumor development. Rats treated weekly for 20 weeks with BOP (10 mg/kg/week i.g.) did not develop any prostatic tumors and all rats died of rectal cancer. Of rats treated similarly with BOP and with testosterone pellets for life following the last injection of BOP, 17% of rats developed prostatic cancer, all of the squamous cell type. Simultaneous testosterone and BOP treatment for 20 weeks followed by testosterone pellets for life resulted in a 39% tumor incidence (three adenocarcinomas, one anaplastic carcinoma, and five squamous cell carcinomas). The overall results suggest that testosterone plays an important role in the initiation of prostatic carcinogenesis, whereas the promotional phase is governed by the interaction of testosterone with other factors.

Beta-oxidized N-nitrosoalkylcarbamates as models for DNA alkylation by N-nitrosobis(2-oxopropyl)amine in Syrian hamsters.

A single dose of N-nitrosobis(2-oxopropyl)amine (NDOPA) can selectively induce pancreatic-duct adenocarcinomas in Syrian hamsters. Multiple doses or a higher single dose can induce tumours of the liver and other organs. Our earlier studies employing NDOPA systematically labelled with 14C in the three-carbon chain showed that hamster pancreatic DNA is almost exclusively methylated and that the sole source of the methyl group is the alpha carbon of NDOPA. Hamster liver DNA was equally methylated and alkylated by a three-carbon chain. Current studies using generally labelled tritiated NDOPA with a very high specific activity have shown that the three-carbon alkylation is 2-hydroxypropylation. We have identified two adducts isolated from hamster liver DNA, N7-(2-hydroxypropyl)-guanine and O6-(2-hydroxypropyl)guanine, which contain this group, and we have also isolated and identified N7-methylguanine and O6-methylguanine in DNA from hamster liver and pancreas. beta-Oxidized N-nitrosocarbamates, ethyl N-nitroso-2-oxopropylcarbamate (NOPC) and ethyl N-nitroso-2-hydroxypropylcarbamate (NHPC), are useful models for predicting the DNA adducts observed in vivo following NDOPA treatment. Base-catalysed decomposition of NOPC in the presence of exogenous DNA yields five methylated purines (N3-, N7- and O6-methylguanines and N1- and N3-methyladenines). NHPC, a model for N-nitrosamines containing the 2-hydroxypropyl group, reacts with guanosine to yield N7- and O6-(2-hydroxypropyl)guanines.(ABSTRACT TRUNCATED AT 250 WORDS)

Carcinogenicity of N-nitrosobis (2-hydroxypropyl) amine after administration to Syrian hamster skin.

Weekly application of N-nitrosobis (2-hydroxypropyl) amine (BHP) at a dose of 50 mg/application to the skin of the neck and flank organ of male Syrian golden hamsters induced no local lesions. However, nearly all treated animals developed internal tumors, primarily of pancreatic, hepatic, respiratory and colorectal origins. Results from this and previous studies indicate that the local carcinogenic effect of nitrosamines depends on the molecular structure of the carcinogen, rather than on tissue specificity. Furthermore, some common types of human cancer could be induced by absorption of specific nitrosamines through skin.

Modification of pancreatic carcinogenesis in the hamster model. VIII. Inhibitory effect of exogenous insulin.

The effect of exogenous insulin, which has been known to suppress beta-cell function of islets, was investigated on pancreatic carcinogenesis induced by N-nitrosobis(2-oxopropyl) amine [(BOP) CAS: 60599-38-4; 2,2'-dioxo-N-nitrosodipropylamine]. Three groups of Syrian golden hamsters were treated sc once with BOP (20 mg/kg body wt) simultaneously with (group 1), 120 minutes before (group 2), or 120 minutes after (group 3) a single sc injection of porcine insulin (5 U/kg body wt). Group 4 was a BOP-treated control. Survivors were killed 46 weeks after BOP administration, and the pancreas, common duct, and gallbladder were examined histologically. When given 120 minutes before or after BOP, insulin inhibited the induction of benign and malignant pancreatic lesions in a statistically significant fashion. However, the simultaneous administration of BOP also led to similar (although not statistically significant) results as did the administration of insulin 120 minutes after BOP. Insulin also seemed to inhibit tumor induction in the common duct and gallbladder, regardless of when it was administered; however, the differing incidence was statistically significant only in hamsters from group 3 killed at the experiment's end. The overall data suggest that the inhibitory effect of exogenous insulin on pancreatic carcinogenicity is not merely through islet cells, but rather through other (or additional) mechanisms.

Modification of pancreatic carcinogenesis in the hamster model. XI. Inhibitory effect of pilocarpine hydrochloride.

Pilocarpine hydrochloride (PH) was administered as a single sc injection (15 mg/kg body wt) to outbred Syrian golden hamsters either prior to, simultaneously with, or after a single 20-mg/kg body weight dose of the pancreatic carcinogen N-nitrosobis(2-oxopropyl)amine (BOP). An additional group was treated with PH, once before and once simultaneously with BOP; another group received PH daily for life after BOP and controls were given BOP only. Surviving hamsters were killed 46 weeks after BOP treatment. PH significantly inhibited pancreatic ductal-ductular cancer induction, whether it was given once before, simultaneously with, or after BOP. A more pronounced inhibitory effect was seen when PH was administered once before and once simultaneously with BOP. However, daily injection of PH did not alter the carcinoma incidence over the BOP control value. The possible mechanisms are discussed.

Modification of pancreatic carcinogenesis in the hamster model. 6. The effect of ductal ligation and excision.

The effect of ligation and excision of the pancreatic duct in pancreatic carcinogenesis was examined in the hamster model. Animals were treated with a single dose (20 mg/kg body weight) of N-nitrosobis(2-oxopropyl)amine (BOP) either immediately (Group 1) or on Days 1 (Group 2), 3 (Group 3) or 7 (Group 4) after ligation and excision of the duct of the splenic lobe. Group 5 received BOP shortly after laparoscopy, and Group 6 consisted of BOP-treated controls. All hamsters were killed 46 weeks after BOP treatment. The results showed that despite advanced atrophy of the splenic lobe distal to the excised duct in Groups 1-4, some hamsters in Groups 2, 3, and 4 showed hyperplasia, dysplasia, and increased mitotic activities of ductal and ductular cells. However, carcinomas in the duct-excised atrophic lobe were found only in Groups 1-3. These data indicate that BOP carcinogenesis is mediated through blood circulation, and that cancer development is not inhibited in the duct-excised lobe for up to 3 days after surgery. However, in the entire pancreas, a significant reduction in tumor incidence was seen when the carcinogen was given immediately, or to a lesser extent, 1 day after surgery, regardless of whether or not excision was made. On the contrary, BOP, when given 3 and 7 days after duct excision, enhanced tumor development in the nonexcised (intact) pancreas, compared with other test groups and with BOP controls. Both inhibition and enhancement seemed due to a proportional decrease and increase, respectively, of BOP-responsive cells throughout the intact pancreas.

Modification of pancreatic carcinogenesis in the hamster model. XII. Dose-related effect of ethanol.

Ethanol (E) was given to outbred Syrian golden hamsters in drinking water at a 5% (wt/vol) concentration for life beginning either before or after a single dose of N-nitrosobis(2-oxopropyl)amine (BOP). No effects on tumor induction were seen in the pancreas or in other BOP target tissues (e.g., the common duct and gallbladder), whether E was given immediately after or 4 weeks before and immediately after BOP. These results sharply conflicted with our previous findings in which a higher concentration of E (25% wt/vol) inhibited BOP-induced pancreatic lesions, and they indicated a dose-related action of E on pancreatic carcinogenesis. Development of a few acinar cell foci in hamsters treated with BOP and E, but not in those treated with E alone or BOP alone, indicated that E in this concentration alters pancreatic functions without modifying carcinogenesis.