Land use and air quality in urban environments: Human health risk assessment due to inhalation of airborne particles.

Particle matter (PM) and its associated compounds are a serious problem for urban air quality and a threat to human health. In the present study, we assessed the intraurban variation of PM, and characterized the human health risk associated to the inhalation of particles measured on PM filters, considering different land use areas in the urban area of Cordoba city (Argentina) and different age groups. To assess the intraurban variation of PM, a biomonitoring network of T. capillaris was established in 15 sampling sites with different land use and the bioaccumulation of Co, Cu, Fe, Mn, Ni, Pb and Zn was quantified. After that, particles were collected by instrumental monitors placed at the most representative sampling sites of each land use category and an inhalation risk was calculated. A remarkable intraurban difference in the heavy metals content measured in the biomonitors was observed, in relation with the sampling site land use. The higher content was detected at industrial areas as well as in sites with intense vehicular traffic. Mean PM10 levels exceeded the standard suggested by the U.S. EPA in all land use areas, except for the downtown. Hazard Index values were below EPA's safe limit in all land use areas and in the different age groups. In contrast, the carcinogenic risk analysis showed that all urban areas exceeded the acceptable limit (1 × 10-6), while the industrial sampling sites and the elder group presented a carcinogenic risk higher that the unacceptable limit. These findings validate the use of T. capillaris to assess intraurban air quality and also show there is an important intraurban variation in human health risk associated to different land use.

Strain Doping: Reversible Single-Axis Control of a Complex Oxide Lattice via Helium Implantation.

We report on the use of helium ion implantation to independently control the out-of-plane lattice constant in epitaxial La(0.7)Sr(0.3)MnO(3) thin films without changing the in-plane lattice constants. The process is reversible by a vacuum anneal. Resistance and magnetization measurements show that even a small increase in the out-of-plane lattice constant of less than 1% can shift the metal-insulator transition and Curie temperatures by more than 100 °C. Unlike conventional epitaxy-based strain tuning methods which are constrained not only by the Poisson effect but by the limited set of available substrates, the present study shows that strain can be independently and continuously controlled along a single axis. This permits novel control over orbital populations through Jahn-Teller effects, as shown by Monte Carlo simulations on a double-exchange model. The ability to reversibly control a single lattice parameter substantially broadens the phase space for experimental exploration of predictive models and leads to new possibilities for control over materials' functional properties.

Juvenile, adult and late-onset systemic lupus erythematosus: a long term follow-up study from a geographic and ethnically homogeneous population.

OBJECTIVES: This paper aims to identify clinical and serological differences, damage accrual and mortality, in juvenile, adult and late-onset SLE. METHODS: We conducted our study with patients fulfilling SLE classification criteria taken from the Hospital Gregorio Marañon Autoimmune Systemic Rheumatic Diseases' Registry (1986 to 2012). Clinical characteristics, laboratory data and therapies used during the course of the disease were analysed with patients divided into 3 groups: juvenile-onset (≤ 18 years), adult-onset (19-50) and late onset (>50 years). RESULTS: Four hundred and forty-five patients were included. Renal disease and cutaneous manifestations were more frequent in the juvenile-onset group at disease onset. During follow-up, juvenile-onset group presented a higher incidence of renal disease, malar rash, Raynaud's phenomenon, cutaneous vasculitis, and neuropsychiatric manifestations than the other two groups. Arthritis and lymphopoenia were more frequent in the adult-onset group. Arterial hypertension and neoplasm were more frequent in the late-onset group. Low serum complement, anti-dsDNA, anti-U1RNP and anti-Sm antibodies were more common in the juvenile-onset group. Patients with late-onset SLE had more damage accrual. Thirty-seven patients (8.3%) died during the study. All-cause mortality was significantly higher in the late-onset group. Age at disease onset >50 years was an independent risk factor for damage accrual (OR, 2.2; 95%CI, 1.1-4.6; p=0.029) and mortality (OR, 2.6; 95%CI, 1.1-6.3; p=0.03). CONCLUSIONS: We found significant differences in clinical and serological profiles between juvenile, adult and late-onset SLE. The most significant of which was a higher prevalence of neuropsychiatric and renal complications as well as different autoantibody signatures for the juvenile-onset group.

Synthesis of nanowires via helium and neon focused ion beam induced deposition with the gas field ion microscope.

The ion beam induced nanoscale synthesis of platinum nanowires using the trimethyl (methylcyclopentadienyl)platinum(IV) (MeCpPt(IV)Me3) precursor is investigated using helium and neon ion beams in the gas field ion microscope. The He(+) beam induced deposition resembles material deposited by electron beam induced deposition with very small platinum nanocrystallites suspended in a carbonaceous matrix. The He(+) deposited material composition was estimated to be 16% Pt in a matrix of amorphous carbon with a large room-temperature resistivity (∼3.5 × 10(4)-2.2 × 10(5) µΩ cm) and temperature-dependent transport behavior consistent with a granular material in the weak intergrain tunnel coupling regime. The Ne(+) deposited material has comparable composition (17%), however a much lower room-temperature resistivity (∼600-3.0 × 10(3) µΩ cm) and temperature-dependent electrical behavior representative of strong intergrain coupling. The Ne(+) deposited nanostructure has larger platinum nanoparticles and is rationalized via Monte Carlo ion-solid simulations which show that the neon energy density deposited during growth is much larger due to the smaller ion range and is dominated by nuclear stopping relative to helium which has a larger range and is dominated by electronic stopping.

Dataset for evaluating WRF-Chem sensitivity to biogenic emission inventories in a tropical region. Global online model (MEGAN) vs local offline model (BIGA).

This article presents a dataset comparing emissions of Biogenic Volatile Organic Compounds (BVOC) in a zone of complex topography in the tropical Andes, which presents elevations ranging from 250 to more than 4000 m above sea level in a radius of only 50 km. Two approximations were evaluated, (1) online with the Model of Emissions of Gases and Aerosols from Nature (MEGAN) coupled with the Weather Research and Forecast model with Chemistry (WRF-Chem) and (2) offline applying the Biogenic Altitudinal Gradient Model (BIGA). Modeled concentrations of pollutants (mainly isoprene and tropospheric ozone) were obtained with WRF-Chem employing the biogenic emission models mentioned previously. This information identified areas where BVOC emissions vary significantly, comparing the global emission inventory (MEGAN) and the local inventory (BIGA). Re-evaluation of the emission factors and land cover assigned to those areas in the global online biogenic models should be considered in order to reduce the uncertainty in the values. In addition, the dataset shows the impact of the biogenic emission inventories on the air quality simulations on a tropical high mountain area, where vegetation is diverse, and the altitudinal changes influence meteorological variables.

Application of infrared thermography in diagnosing peripherally inserted central venous catheter infections in children with cancer.

APPROACH: Children affected by oncological diseases are often fitted with central venous catheters (CVCs). Catheter infection is a frequent complication, sometimes accompanied by thrombosis. A case/control-type pilot study of children with oncological diseases fitted with a CVC is here designed. OBJECTIVE: The objective of this preliminary study is to use infrared thermography to discern whether there is an infection in patients with a CVC and, if so, to undertake a close follow-up of its evolution, after administering a therapy. Thermal asymmetry by mean and maximum temperatures (temperature affected ROI - temperature contralateral ROI) is measured. MAIN RESULTS: In all cases with catheter infection, thermal asymmetry values were higher than in controls without infection, allowing us to assess improvement after starting the treatment. SIGNIFICANCE: These preliminary results are satisfactory because they reflect the advantages of using infrared thermography on oncological child patients, as it is a harmless, non-contact, accessible and quick technique, allowing us to reduce the use of ionizing radiation and quantify the clinical signs of inflammation, which are otherwise only qualitatively detectable in clinical examination. By doing so, it may be possible to anticipate infection and provide early treatment, and, moreover, to observe whether there is any complication after starting a treatment. More studies need to be undertaken with an extensive paediatric population to establish reference values.

Regulation of ErbB-4 endocytosis by neuregulin in GABAergic hippocampal interneurons.

Neuregulin (NRG)/ErbB receptor signaling pathways have recently been implicated in the reversal of long-term potentiation at hippocampal glutamatergic synapses. Moreover, polymorphisms in NRG-1 and ErbB-4 genes have been linked to an increased risk for developing schizophrenia. ErbB-4 is highly expressed at glutamatergic synapses where it binds to PSD-95 via its carboxyl terminal T-V-V sequence. Here we investigated the expression, localization and trafficking of ErbB-4 in cultured hippocampal neurons by immunocytochemistry, surface protein biotinylation, and live labeling of native receptors. We show that neuronal ErbB-4 is detected at its highest levels in GABAergic interneurons, as observed in vivo. ErbB-4 immunoreactivity precedes PSD-95 expression, with ErbB-4 cluster initially forming in the absence of, but later associating with, PSD-95-positive puncta. By surface protein biotinylation, the fraction of ErbB-4 receptors on the plasma membrane increases from 30% to 65% between 6 and 16 days in vitro (DIV). Interestingly, 30 min of NRG stimulation triggers measurable ErbB-4 receptor internalization at DIV 16, despite increased colocalization with PSD-95. We also investigated the role of TNFalpha-converting enzyme (TACE)-mediated receptor processing in regulating ErbB-4 surface expression. We found that the cleavage-resistant JM-b isoform accounts for 80% of all ErbB-4 transcripts in cultured hippocampal neurons. Receptor stimulation or treatment with phorbol esters does not induce detectable ErbB-4 processing, indicating that neurons mostly rely on endocytosis of the intact receptor to regulate ErbB-4 surface expression. These results enhance our understanding of the regulation of ErbB-4--mediated signaling at glutamatergic synapses.

Oral sildenafil citrate lacks genotoxicity and cytotoxicity in a primate model: Callithrix jacchus.

OBJECTIVE: To determine sildenafil citrate (SC) genotoxicity and cytotoxicity in the Callithrix jacchus. STUDY DESIGN: Fifteen organisms were assigned to one of three groups as follows: experimental (25 mg/kg of SC); negative control (glucose solution 5%); and positive control (3 mg/kg of cytocine arabinoside). Systemic hemodynamic changes were monitored in each animal before and after each treatment. A drop of blood was obtained before and after the treatment at 24-120 h. Smears were made and the frequency of micronucleated erythrocytes (MNE), micronucleated polychromatic erythrocytes (MNPCE) and polychromatic erythrocytes (PCE) was counted. RESULTS: No significant differences in MNE, MNPCE and PCE were found in the group that received sildenafil and negative control. A significant increase in genotoxicity and cytotoxicity was observed in the positive control group. No changes were observed in systemic hemodynamic changes. CONCLUSION: The macro-dose of SC lacks genotoxic, cytotoxic or systemic hemodynamic changes effects in this species.

Environmental variation of PCDD/Fs and dl-PCBs in two tropical Andean Colombian cities using passive samplers.

Passive air-sampling data of polychlorinated dibenzo-p-dioxins (PCDDs), polychlorinated dibenzofurans (PCDFs) and dioxin-like polychlorinated biphenyls (dl-PCBs) taken in Manizales (a medium-sized city) and Bogotá (a megacity), Colombia, were analyzed in order to identify potential sources of pollution and the possible influence of meteorological variables like temperature and precipitation. The results indicate important differences in levels of PCDD/Fs and dl-PCBs between Bogotá and Manizales, attributed to differences in site characteristics and potential local/regional sources. Higher PCDD/Fs concentrations were observed in Bogotá (373fg/m(3)) compared to those observed in Manizales, with mean levels ranging from 64fg/m(3) in a residential zone to 151fg/m(3) around a vehicular-influenced area. Higher dl-PCBs concentrations were observed in the industrial area of Manizales compared to those observed in Bogotá, with mean levels of 6668fg/m(3) and 4388fg/m(3) respectively. In terms of PCDD/Fs congener distribution, there was a predominance of octachlorodibenzodioxin (OCDD) followed by 1,2,3,4,6,7.8-heptachlorodibenzofuran (HpCDF) congeners, with both cities showing higher levels in zones of high vehicular activity. Industrial influence was most evident in dl-PCB levels. In comparison to the mean levels of dl-PCB congeners obtained in the vehicular zones of Bogotá and Manizales, the industrially influenced sampling stations showed higher concentrations of dl-PCB congeners. Passive sampling results suggested that congener concentration profiles are characteristic of their different emission sources, and can be used to distinguish between their industrial or vehicular origins.

Production of Cost-Effective Mesoporous Materials from Prawn Shell Hydrocarbonization.

In this work, prawn shell was studied as raw material for the production of mesoporous adsorbents via hydrocarbonization, studying the effect of temperature and time on the process reactivity and final characteristics of the hydrochars. By suitable characterization technique analyses (N2 adsorption at 77 K, SEM observation, ultimate analysis, surface composition), the materials were examined. It was found that in both cases mesoporous materials with low values of S BET due to the presence of CaCO3 on the material structure. In order to provide a potential application for these materials, the adsorption behaviour of hydrochars (HCs) as well as that of pristine prawn shells and ashes from prawn shell combustion was studied for the first time with the model compound p-nitrophenol (PNP). The results indicated that HC treatment was beneficial and enhanced adsorption performance, especially at high values of equilibrium concentration, attaining adsorption capacities up to 1.6 mg g(-1).

Prognostic factors for trabeculectomy failure in a Cuban population.

OBJECTIVE: To identify the prognostic factors for mid-term trabeculectomy failure. METHOD: A prospective cohort study was conducted on 113 eyes (113 patients) that had undergone a trabeculectomy for primary open or closed angle, pigmentary, or juvenile glaucoma. Surgical failure was defined if intraocular pressure was equal or more than 18mmHg with medication (two or more drops), after 1-4 postoperative years. The relative risk was calculated and a logistic regression analysis was performed. RESULTS: Previous trabeculectomy, preoperative intraocular pressure ≥ 31mmHg, black race, and advanced glaucoma increased the failure risk by 7.9 times (P=.036), 5.3 times (P=.011) and 4.7 times (P=.028, and P=.027), respectively. The addition of two or more factors increased the risk by 6.4 times (P<.001). It was not affected by age, sex, pre-operative drops, or surgical complication. CONCLUSIONS: Previous trabeculectomy, pre-operative intraocular pressure ≥ 31mmHg, black race, and advanced glaucoma are prognostic factors for trabeculectomy failure, in decreasing order of their association with surgical failure. The addition of two or more factors increased the risk of failure. In those situations, the use of trans- operative anti-metabolites is suggested.

Squalamine treatment of human tumors in nu/nu mice enhances platinum-based chemotherapies.

Squalamine, an antiangiogenic aminosterol, is presently undergoing Phase II clinical trials in cancer patients. To broaden our understanding of the clinical potential for squalamine, this agent was evaluated in nu/nu mouse xenograft models using the chemoresistant MV-522 human non-small cell lung carcinoma and the SD human neuroblastoma lines. Squalamine was studied alone and in combination with either cisplatin or paclitaxel plus carboplatin. Squalamine alone produced a modest MV-522 tumor growth inhibition (TGI) and yielded a TGI with cisplatin that was better than cisplatin alone. Squalamine also significantly enhanced the activity of paclitaxel/carboplatin combination therapy in the MV-522 tumor model. Squalamine similarly improved the effectiveness of cisplatin in producing TGI when screened against the SD human neuroblastoma xenograft. Xenograft tumor shrinkage was seen for the MV-522 tumor in combination treatments including squalamine, whereas no tumor shrinkage was seen when squalamine was omitted from the treatment regimen. To gain a greater understanding of the mechanism by which squalamine inhibited tumor growth in the xenograft studies, in vitro experiments were carried out with vascular endothelial growth factor-stimulated human umbilical vein endothelial cells in culture exposed to squalamine. Squalamine treatment was found to retard two cellular events necessary for angiogenesis, inducing disorganization of F-actin stress fibers and causing a concomitant reduction of detectable cell the surface molecular endothelial cadherin (VE-cadherin). We propose that the augmentation by squalamine of cytotoxicity from platinum-based therapies is attributable to interference by squalamine with the ability of stimuli to promote endothelial cell movement and cell-cell communication necessary for growth of new blood vessels in xenografts after chemotherapeutic injury to the tumor.

Independent and combined influence of neonatal and current body composition on academic performance in youth: The UP & DOWN Study.

BACKGROUNDS: Unhealthy body composition is a cause for concern across the lifespan. OBJECTIVE: The objective of this study was to examine the independent and combined associations between neonatal and current body composition with academic performance among youth. METHODS: This cross-sectional study was conducted with a total of 1557 youth (745 girls) aged 10.4 ± 3.4 years. Birth weight and length at birth were self-reported. Current body composition was assessed by body mass index (BMI), waist circumference (WC) and percentage of body fat (BF%). Academic performance was assessed through schools records. RESULTS: Birth weight was related to all academic variables in boys, independent of potential confounders, including BMI; whereas WC, BMI and BF% were related to all academic performance indicators in both boys and girls, independent of potential confounders, including birth weight (all P < 0.05). In addition, the combined adverse effects of low birth weight and current overweight on academic performance were observed in both boys and girls for grade point average (GPA) indicator. Boys in the group with none adverse effect had significantly higher scores in GPA (score +0.535; 95% confidence interval, 0.082-0.989) than boys in the group of both adverse effects (P < 0.007); among girls, GPA score was higher in the group with none adverse effect than in the groups with one or two adverse effects (P for trend = 0.029). CONCLUSIONS: Neonatal and current body composition, both independently and combined, may influence academic performance in youth.

(S)-13-[(dimethylamino)methyl]-10,11,14,15-tetrahydro-4,9:16, 21-dimetheno-1H, 13H-dibenzo[e,k]pyrrolo[3,4-h][1,4,13]oxadiazacyclohexadecene-1,3(2H)-d ione (LY333531) and related analogues: isozyme selective inhibitors of protein kinase C beta.

Protein kinase C (PKC) is a family of closely related serine and threonine kinases. Overactivation of some PKC isozymes has been postulated to occur in several diseases states, including diabetic complications. Selective inhibition of overactivated PKC isozymes may offer a unique therapeutic approach to disease states such as diabetic retinopathy. A novel series of 14-membered macrocycles containing a N-N'-bridged bisindolylmaleimide moiety is described. A panel of eight cloned human PKC isozymes (alpha, beta I, beta II, gamma, delta, epsilon, sigma, eta) was used to identify the series and optimize the structure and associated activity relationship. The dimethylamine analogue LY333531 (1), (S)-13-[(dimethylamino)methyl]-10,11,14,15-tetrahydro-4,9:16, 21-dimetheno-1H, 13H-dibenzo[e,k]pyrrolo[3,4-h][1,4,13]oxadiazacyclohexadecene++ +-1,3(2H)-dione, inhibits the PKC beta I (IC50 = 4.7 nM) and PKC beta II (IC50 = 5.9 nM) isozymes and was 76- and 61-fold selective for inhibition of PKC beta I and PKC beta II in comparison to PKC alpha, respectively. The additional analogues described in the series are also selective inhibitors of PKC beta. LY333531 (1) exhibits ATP dependent competitive inhibition of PKC beta I and is selective for PKC in comparison to other ATP dependent kinases (protein kinase A, calcium calmodulin, caesin kinase, src tyrosine kinase). The cellular activity of the series was assessed using bovine retinal capillary endothelial cells. Retinal endothelial cell dysfunction has been implicated in the development of diabetic retinopathy. Plasminogen activator activity stimulated by a phorbol ester (4 beta-phorbol 12,13-dibutyrate) in endothelial cells was inhibited by the compounds in the series with ED50 values ranging from 7.5 to 0.21 microM. A comparison of the PKC isozyme and related ATP dependent kinase inhibition profiles is provided for the series and compared to the profile for staurosporine, a nonselective PKC inhibitor. The cellular activity of the series is compared with that of the kinase inhibitor staurosporine.

Vasopressin-induction of the immediate early gene, NGFI-A, in cultured hippocampal glial cells.

Our earlier autoradiographic work had documented a wide distribution of vasopressin receptors in the hippocampus [R.E. Brinton, K.W. Gee, J.K. Wamsley, T.P. Davis, H.I. Yamamura, Regional distribution of putative vasopressin receptors in rat brain and pituitary by quantitative autoradiography, in: Proc. Natl. Acad. Sci. USA, 81 (1984) pp. 7248-7252; C. Chen, R.D. Brinton, T.J. Shors, R.F. Thompson, [Arg 8]-Vasopressin-induction of long lasting potentiation of synaptic transmission in the dentate gyrus, Hippocampus 3 (1993) 193-203.] which suggested the possibility that receptors for vasopressin were present in both neurons and glia. In the periphery, vasopressin is a potent mitogen in select proliferative cell types [E. Rozengurt, A. Legg, P. Pettican, Vasopressin stimulation of mouse 3T3 cell growth, Proc. Natl. Acad. Sci. USA, 76 (1979) pp. 1284-1287.] which also suggested a possible association between vasopressin receptor activation and the proliferative capacity of astrocytes. We therefore investigated whether vasopressin would induce the expression of the immediate early response gene, NGFI-A (also known as zif/268, ZENK, egr-1, krox 24), which is associated with initiation of mitogenesis [M. Sheng, M.E. Greenberg, The regulation and function of c-fos and other immediate early genes in the nervous system, Neuron, 4 (1990) pp. 477-485.]. Cultured hippocampal glial cells were exposed to vasopressin or a selective V1 vasopressin receptor agonist and in situ hybridization for NGFI-A mRNA was conducted. Results of these experiments demonstrated that vasopressin induced a highly significant dose-dependent increase in the number of cells expressing NGFI-A. Studies to determine the receptor subtype mediating vasopressin induction of NGFI-A were conducted utilizing the specific V1 agonist, [Phe2, Ile3, Orn8]-vasopressin. The V1 receptor agonist induced a highly significant dose dependent increase in the number of grains per NGFI-A positive cell. Time course analysis demonstrated that V1 agonist induction of NGFI-A occurred within 5 min, was maximally induced at 15 min of exposure and exhibited a gradual decline within 30 min of exposure which continued to decline over the 60 min time course. Glial cell responsivity was selective in that vasopressin and V1 agonist induction of NGFI-A occurred in a subpopulation of glial cells. Within a sea of glial cells, vasopressin and V1 agonist would induce islands of NGFI-A positive cells. Results of combined immunocytochemical labeling for the astrocyte specific marker, GFAP, and in situ hybridization for NGFI-A demonstrated that V1 agonist-induced NGFI-A expression occurred in GFAP positive cells. We observed no evidence for V1 agonist induction of NGFI-A in neurons. Collectively, these data document that vasopressin, acting via V1 vasopressin receptors, induces a highly significant increase in NGFI-A expression in select GFAP positive hippocampal astrocytes. To our knowledge, these data are the first report of a vasopressin mediated response in hippocampal glial cells. The potential functional significance of these findings is discussed.

Sildenafil causes a dose- and time-dependent downregulation of phosphodiesterase type 6 expression in the rat retina.

OBJECTIVES: Some authors have advocated the daily use of sildenafil for prophylaxis against, or treatment of, erectile dysfunction. However, no information has been published to support such a dosage regimen. The safety profile of uninterrupted use of sildenafil has not been evaluated as it pertains to alteration of PDE type 6 in the retina. In the present study we investigated whether short- or long-term exposure to a variety of sildenafil doses affect the expression of an enzyme important in the normal phototransduction cascade. METHODS: Sustained-release sildenafil pellets were implanted in 120-day-old male rats with concentrations from 1-200mg. Rat retinal tissue was harvested 7, 14, and 29 days after implantation. Quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) using GAPDH as an endogenous internal standard was used to quantitate PDE type 6 gene expression. RESULTS: Expression of PDE type 6 was upregulated after 7 days with dosages < or =5 mg (P<0.02). Significant downregulation of PDE type 6 expression was first noted with high dose sildenafil 14 days after implantation (P<0.02). Expression of PDE type 6 was significantly and profoundly downregulated 29 days after implantation for all pellet formulations > or =10 mg (P<0.01). CONCLUSIONS: Sildenafil downregulates PDE type 6 expression in a dose- and time-dependent fashion. These findings support the explanation that PDE type 6 inhibition causes the dose-dependent clinical effects of visual disturbance in men taking sildenafil. Implications for long-term, daily use of sildenafil in men are not clear.

Analysis of NOS isoform changes in a post radical prostatectomy model of erectile dysfunction.

Optimal treatment of erectile dysfunction (ED) following radical prostatectomy remains a subject of much controversy and is a significant concern for prostate cancer patients requiring surgical intervention. Neural stimulation involving nitric oxide synthase (NOS) is a crucial aspect of the normal erection process. In this study NOS isoform interaction was evaluated to improve our understanding of molecular changes pertaining to erection post radical prostatectomy. Bilateral cavernous nerve (CN) resected and control adult male Sprague-Dawley rats were killed 7, 14 and 21 days after injury. RT-PCR, in situ hybridization, Western blot and immunohistochemical analysis were used to evaluate changes in NOS isoform expression and distribution. NOS-I protein was dramatically decreased after CN injury while NOS-III and NOS-II remained unchanged. A profound decrease in smooth muscle and endothelium was observed in the corpora. To our knowledge this is the first report of differential altered NOS isoform protein abundance under conditions which mimic radical prostatectomy. These results show the importance of maintaining at least partial innervation of the penis after surgical intervention and that endothelial and smooth muscle changes resulting from loss of innervation may account for the ED observed in prostatectomy patients.

Protein and gene expression of nitric oxide synthase isoforms I and III in the rat penile shaft.

Nitric oxide synthase (NOS) plays a key role in penile smooth muscle relaxation through the regulation of nitric oxide (NO). NO is a major neurotransmitter in the autonomic nervous system, and alteration of its activity has been implicated in erectile dysfunction. The objectives of this study were twofold: 1) to demonstrate and localize the NOS protein isoforms I and III in the normal rat penis, and 2) to identify and quantitate NOS I and III gene expression in the normal rat penis. The gene and protein product of NOS isoforms I and III are expressed in rat penile tissue. Protein expression of NOS I was confined primarily to neuronal tissue, while NOS III protein expression was identified primarily in both cavernosal smooth muscle and endothelium. The presence of both NOS I and III was confirmed in the penile shaft by Western blot. Quantitation of NOS I and III gene expression by reverse transcription-polymerase chain reaction revealed NOS III to be more highly expressed than that of NOS I in the rat penile shaft. NOS I and III protein and gene products are both expressed in normal rat penile tissue. Protein expression is localized primarily to neuronal tissue for NOS I, whereas NOS III is localized primarily to cavernosal smooth muscle and endothelium. NOS III gene expression is greater than that of NOS I in the normal rat penile shaft. These findings support the possibility that penile erection is regulated by different NOS isoforms released from neural, endothelial, and smooth muscle sources.

Hand-assisted vs. retroperitoneal laparoscopic nephrectomy.

PURPOSE: We retrospectively compared our initial experience with the hand-assisted and retroperitoneal laparoscopic nephrectomy techniques to determine if there are important differences between these approaches. PATIENTS AND METHODS: Twenty-four laparoscopic cases consisting of 12 hand-assisted and 12 retroperitoneal nephrectomies were compared. All cases but one were radical nephrectomies with intact specimen extraction performed for suspected stage T1 neoplasms. Data were collected from medical records and a postoperative questionnaire. To determine if significant learning curves existed, the first six nephrectomies in each group were compared with the second six nephrectomies on the basis of operative criteria. The two groups did not differ significantly in age, body mass index, ASA rating, or number of previous abdominal operations. RESULTS: Although the mean tumor volume was greater in the hand-assisted group than the retroperitoneal group, the difference did not quite reach statistical significance (91.19 v 24.7 cc3; P = 0.06). The mean operative time, estimated blood loss, narcotic use (milligrams of intravenous morphine equivalent), hours to oral intake, hospital stay, and estimated percent activity at 2 weeks for the hand-assisted group (238.33 min, 293.75 mL, 35.7 mg, 17.56 hours, 4.4 days, 74.75%, respectively) were not significantly different from the values in the retroperitoneal group (255.83 min, 141.67 mL, 24.5 mg, 22.36 hours, 3.6 days, 76.91%). We found no significant difference in the mean operative times for the first and second six cases in either group. CONCLUSION: In the initial experience and comparison of hand-assisted and retroperitoneal laparoscopic nephrectomy, we found no significant differences in operative time, estimated blood loss, narcotic usage, hours to oral intake, hospital stay, or activity level at 2 weeks postoperatively. A randomized trial is under way at our institution.

Hand-assisted laparoscopic radical nephrectomy: the experience of the inexperienced.

PURPOSE: We retrospectively examined the experience of novice laparoscopic surgeons performing hand-assisted laparoscopic radical nephrectomy. The purpose was to determine if urologists with minimal laparoscopic training could perform hand-assisted laparoscopic nephrectomies in a safe and efficient manner. MATERIALS AND METHODS: The first six hand-assisted laparoscopic radical nephrectomies performed by four different urology residents at the Chicago Lakeside VA hospital were reviewed. The residents included three chief urology residents and one postgraduate year 3 urology resident. None of the residents had taken any laparoscopic course, and all had limited exposure to the hand-assisted technique. In all cases, the residents performed the entire operation. The patients were evaluated for operative time, tumor size, body mass index, and ASA score. RESULTS: All six procedures were completed without conversion to the open technique. The average operating time was 215.8 minutes, and the time from incision to organ removal averaged 140.8 minutes. The average estimated blood loss was 166 mL. Complications included an intraoperative diaphragmatic injury (recognized and repaired laparoscopically) and one postoperative ileus. CONCLUSION: Hand-assisted laparoscopic radical nephrectomy can be performed safely and efficiently by urologists with minimal laparoscopic experience.