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Targeting metabolomic pathways is a promising strategy for cancer treatment. Alterations in the metabolomic state have also an epigenetic impact, making the metabolomic studies even more interesting. We explored metabolomic changes in the blood plasma of patients with primary and secondary lung cancer and tried to explore their origin. We also applied a discrimination algorithm to the data. In the study, blood samples from 132 patients with primary lung cancer, 47 with secondary lung cancer, and 77 subjectively healthy subjects without any cancer history were used. The samples were measured by NMR spectroscopy. PCA and PLS-DA analyses did not distinguish between patients with primary and secondary lung tumors. Accordingly, no significantly changed levels of plasmatic metabolites were found between these groups. When comparing with healthy controls, significantly increased glucose, citrate, acetate, 3-hydroxybutyrate, and creatinine balanced with decreased pyruvate, lactate, alanine, tyrosine, and tryptophan were found as a common feature of both groups. Metabolomic analysis of blood plasma showed considerable proximity of patients with primary and secondary lung cancer. The changes observed can be partially explained as cancer-derived and also as changes showing ischemic nature. Random Forrest discrimination based on the relative concentration of metabolites in blood plasma performed very promising with AUC of 0.95 against controls; however noticeable parts of differencing metabolites are overlapping with those observed after ischemic injury in other studies.

The formation of new blood vessels from previous ones, angiogenesis, is critical in tissue repair, expansion or remodeling in physiological processes and in various pathologies including cancer. Despite that, the development of anti-angiogenic drugs has great potential as the treatment of cancer faces many problems such as development of the resistance to treatment or an improperly selected therapy approach. An evaluation of predictive markers in personalized medicine could significantly improve treatment outcomes in many patients. This comprehensive review emphasizes the anticancer potential of flavonoids mediated by their anti-angiogenic efficacy evaluated in current preclinical and clinical cancer research. Flavonoids are important groups of phytochemicals present in common diet. Flavonoids show significant anticancer effects. The anti-angiogenic effects of flavonoids are currently a widely discussed topic of preclinical cancer research. Flavonoids are able to regulate the process of tumor angiogenesis through modulation of signaling molecules such as VEGF, MMPs, ILs, HIF or others. However, the evaluation of the anti-angiogenic potential of flavonoids within the clinical studies is not frequently discussed and is still of significant scientific interest.

Objectives Abdominal aortic aneurysm (AAA) and its complications are among the most serious cardiovascular diseases and its occurrence has risen sharply in recent years. The aim of this pilot study is to explore the relationship between the methylation of matrix metalloproteinases and tissue inhibitors of the metalloproteinases genes' promoter region, and abdominal aortic aneurysm (AAA) through the detection of the methylation status of MMP2, TIMP2, TIMP1, and MMP9 genes in peripheral blood. Methods The study included 43 males with verified AAA (case group) and 34 healthy males (control group). The methylation status of the genes' promoter region was detected by methylation-specific polymerase chain reaction (MS-PCR). Results In adominal aortic aneurysm patients, the methylation ratio of MMP2 gene was positive in 9.3 % (4 cases), 2.3 % (1 case) had methylated TIMP2 gene, 7.0 % (3 cases) had methylated TIMP1 gene, while the methylation ratio of MMP9 gene was positive in 93.0 % (40 cases). In the control group, MMP2 gene was found to be methylated in 5.9 % (2 cases), 5.9 % of cases had methylated TIMP2 and TIMP1 genes (2 cases), and MMP9 gene was found to be methylated in 91.2 % (31 cases). Conclusion In our pilot study, we found no association between DNA methylation of gelatinases and their tissue inhibitors, and the development of an abdominal aortic aneurysm (Tab. 2, Fig. 1, Ref. 27).

The global pandemic of coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is having a tremendous impact on the global economy, health care systems and the lives of almost all people in the world. The Central European country of Slovakia reached one of the highest daily mortality rates per 100,000 inhabitants in the first 3 months of 2021, despite implementing strong prophylactic measures, lockdowns and repeated nationwide antigen testing. The present study reports a comparison of the performance of the Standard Q COVID-19 antigen test (SD Biosensor) with three commercial RT-qPCR kits (vDetect COVID-19-MultiplexDX, gb SARS-CoV-2 Multiplex-GENERI BIOTECH Ltd. and Genvinset COVID-19 [E]-BDR Diagnostics) in the detection of infected individuals among employees of the Martin University Hospital in Slovakia. Health care providers, such as doctors and nurses, are classified as “critical infrastructure”, and there is no doubt about the huge impact that incorrect results could have on patients. Out of 1231 samples, 14 were evaluated as positive for SARS-CoV-2 antigen presence, and all of them were confirmed by RT-qPCR kit 1 and kit 2. As another 26 samples had a signal in the E gene, these 40 samples were re-isolated and subsequently re-analysed using the three kits, which detected the virus in 22, 23 and 12 cases, respectively. The results point to a divergence not only between antigen and RT-qPCR tests, but also within the “gold standard” RT-qPCR testing. Performance analysis of the diagnostic antigen test showed the positive predictive value (PPV) to be 100% and negative predictive value (NPV) to be 98.10%, indicating that 1.90% of individuals with a negative result were, in fact, positive. If these data are extrapolated to the national level, where the mean daily number of antigen tests was 250,000 in April 2021, it points to over 4700 people per day being misinterpreted and posing a risk of virus shedding. While mean Ct values of the samples that were both antigen and RT-qPCR positive were about 20 (kit 1: 20.47 and 20.16 for Sarbeco&nbsp, E and RdRP, kit 2: 19.37 and 19.99 for Sarbeco&nbsp, E and RdRP and kit 3: 17.47 for ORF1b/RdRP), mean Ct values of the samples that were antigen-negative but RT-qPCR-positive were about 30 (kit 1: 30.67 and 30.00 for Sarbeco&nbsp, E and RdRP, kit 2: 29.86 and 31.01 for Sarbeco&nbsp, E and RdRP and kit 3: 27.47 for ORF1b/RdRP). It confirms the advantage of antigen test in detecting the most infectious individuals with a higher viral load. However, the reporting of Ct values is still a matter of ongoing debates and should not be conducted without normalisation to standardised controls of known concentration.

Increased level of homocysteine (hHcy) in plasma is an accompanying phenomenon of many diseases, including a brain stroke. This study determines whether hyperhomocysteinemia (which is a risk factor of brain ischemia) itself or in combination with ischemic preconditioning affects the ischemia-induced neurodegenerative changes, generation of reactive oxygen species (ROS), lipoperoxidation, protein oxidation, and activity of antioxidant enzymes in the rat brain cortex. The hHcy was induced by subcutaneous administration of homocysteine (0.45 mu mol/g body weight) twice a day in 8 h intervals for 14 days. Rats were preconditioned by 5 min ischemia. Two days later, 15 min of global forebrain ischemia was induced by four vessel's occlusion. The study demonstrates that in the cerebral cortex, hHcy alone induces progressive neuronal cell death and morphological changes. Neuronal damage was associated with the pro-oxidative effect of hHcy, which leads to increased ROS formation, peroxidation of lipids and oxidative alterations of cortical proteins. Ischemic reperfusion injury activates degeneration processes and de-regulates redox balance which is aggravated under hHcy conditions and leads to the augmented lipoperoxidation and protein oxidation. If combined with hHcy, ischemic preconditioning could preserve the neuronal tissue from lethal ischemic effect and initiates suppression of lipoperoxidation, protein oxidation, and alterations of redox enzymes with the most significant effect observed after prolonged reperfusion. Increased prevalence of hyperhomocysteinemia in the Western population and crucial role of elevated Hcy level in the pathogenesis of neuronal disorders makes this amino acid as an interesting target for future research. Understanding the multiple etiological mechanisms and recognition of the co-morbid risk factors that lead to the ischemic/reperfusion injury and ischemic tolerance is therefore important for developing therapeutic strategies in human brain stroke associated with the elevated level of Hcy.

Interleukin-18 (IL-18), pro-inflammatory cytokine, plays important role in antitumor immunity. Polymorphisms in the IL-18 gene may lead to its altered production/activity and such modulate susceptibility to prostate cancer. The aim of this study was to evaluate the relationship between the -607 and +105 polymorphisms in the IL-18 gene and the risk of prostate cancer development and progression in Slovak population. The study was performed using 425 patients with prostate cancer, 270 patients with benign prostatic hyperplasia (BHP) and 263 healthy male controls. The statistically significant association of the -607 AC genotype (OR = 2.24; p < 0.001), CC genotype (OR = 1.86; p = 0.006), as well as C allele (OR = 1.27; p = 0.033) with the higher risk of prostate cancer development was observed. No association of the IL-18 -607 polymorphism and BHP was detected. The subset analysis revealed the significant association of the -607 AC genotype (OR = 2.01; p = 0.008) with development of higher-grade carcinomas (Gleason score ≥7) and the strong association of the -607 AC genotype (OR = 3.11; p < 0.001), CC genotype (OR = 2.96; p < 0.001) as well as C allele (OR = 1.51; p = 0.003) with the higher risk of prostate cancer development in the group of patients with PSA < 10 ng/ml. The -607 AC genotype was also connected with significantly higher IL-18 plasma concentrations. No association between the IL-18 +105 polymorphism and prostate cancer was observed. The analysis of the distribution of the -607 and +105 haplotypes showed significant association of the - 607 C/ + 105 A and - 607 C/ + 105 C haplotypes with the risk of prostate cancer. This study found that the IL-18 -607 promoter polymorphism could contribute to prostate cancer development in Slovak population. Its presence was also associated with development of higher-grade carcinomas and therefore may influences the prognosis and aggressiveness of the disease.

Hyperhomocysteinemia (hHCy) is recognized as a co-morbid risk factor of human stroke. It also aggravates the ischemia-induced injury by increased production of reactive oxygen species, and by the homocysteinylation and thiolation of functional proteins. Ischemic preconditioning represents adaptation of the CNS to sub-lethal ischemia, resulting in increased brain tolerance to subsequent ischemia. We present here an overview of recent data on the homocysteine (Hcy) metabolism and on the genetic and metabolic causes of hHCy-related neuropathologies in humans. In this context, the review documents for an increased oxidative stress and for the functional modifications of enzymes involved in the redox balance in experimentally induced hHCy. Hcy metabolism leads also to the redox imbalance and increased oxidative stress resulting in elevated lipoperoxidation and protein oxidation, the products known to be included in the neuronal degeneration. Additionally, we examine the effect of the experimental hHCy in combination with ischemic insult, and/or with the preischemic challenge on the extent of neuronal degeneration as well as the intracellular signaling and the regulation of DNA methylation. The review also highlights that identification of the effects of co-morbid factors in the mechanisms of ischemic tolerance mechanisms would lead to improved therapeutics, especially the brain tissue.

Today's dynamic healthcare environment demands that healthcare providers explore and implement various strategies to be successful in providing patient care. The Institute of Medicine has challenged healthcare organizations to commit to improving the quality of healthcare by providing safe care

Three parameters are needed to model symmetrical adapters, but not enough equations can be found to solve them. The proposed two-impedance model with one shunt and one series impedance gives consistent results when applied to three different lengths of embedded microstrip transmission lines. This model can be used with more complicated structures than the single-impedance model. © 2004 Wiley Periodicals, Inc. Microwave Opt Technol Lett 42: 50–54, 2004; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/mop.20204

A phenomenological model of magnetic nanoparticle composites consisting of ideal lossless particles with identical properties embedded in a non-magnetic matrix has been developed. The input material parameter for this model include the saturation magnetization (M s ) and the crystal anisotropy field (H k ) of the particles. The relationships between key magnetic properties like the low frequency effective permeability and the FMR frequency, and the material and physical attributes (such as shape, volume fraction, and packing type) of the particles have been identified using an iterative extension of the Bruggeman effective medium theory.

Meconium aspiration in newborns causes lung inflammation and injury, which may lead to meconium aspiration syndrome (MAS). In this study, the effect of the antioxidant N-acetylcysteine on respiratory and inflammatory parameters were studied in a model of MAS. Oxygen-ventilated rabbits were intratracheally given 4 mL/kg of meconium (25 mg/mL) or saline. Thirty minutes later, meconium-instilled animals were administered N-acetylcysteine (10 mg/kg; i.v.), or were left without treatment. The animals were oxygen-ventilated for additional 5 h. Ventilatory pressures, oxygenation, right-to-left pulmonary shunts, and leukocyte count were measured. At the end of experiment, trachea and lung were excised. The left lung was saline-lavaged and a total and differential count of cells in bronchoalveolar lavage fluid (BAL) was determined. Right lung tissue strips were used for detection of lung edema (expressed as wet/dry weight ratio) and peroxidation (expressed by thiobarbituric acid-reactive substances, TBARS). In lung and tracheal strips, airway reactivity to acetylcholine was measured. In addition, TBARS and total antioxidant status were determined in the plasma. Meconium instillation induced polymorphonuclear-derived inflammation and oxidative stress. N-acetylcysteine improved oxygenation, reduced lung edema, decreased polymorphonuclears in BAL fluid, and diminished peroxidation and meconium-induced airway hyperreactivity compared with untreated animals. In conclusion, N-acetylcysteine effectively improved lung functions in an animal model of MAS.

The purpose of this study was to determine the impact of secondary hypoxemia on visual discrimination accuracy after parasagittal fluid percussion injury (FPI). Rats lived singly in test cages, where they were trained to repeatedly execute a flicker-frequency visual discrimination for food. After learning was complete, all rats were surgically prepared and then retested over the following 4-5 days to ensure recovery to presurgery levels of performance. Rats were then assigned to one of three groups [FPI + Hypoxia (IH), FPI + Normoxia (IN), or Sham Injury + Hypoxia (SH)] and were anesthetized with halothane delivered by compressed air. Immediately after injury or sham injury, rats in groups IH and SH were switched to a 13% O2 source to continue halothane anesthesia for 30 min before being returned to their test cages. Anesthesia for rats in group IN was maintained using compressed air for 30 min after injury. FPI significantly reduced visual discrimination accuracy and food intake, and increased incorrect choices. Thirty minutes of immediate posttraumatic hypoxemia significantly (1) exacerbated the FPI-induced reductions of visual discrimination accuracy and food intake, (2) further increased numbers of incorrect choices, and (3) delayed the progressive recovery of visual discrimination accuracy. Thionine stains of midbrain coronal sections revealed that, in addition to the loss of neurons seen in several thalamic nuclei following FPI, cell loss in the ipsilateral dorsal lateral geniculate nucleus (dLG) was significantly greater after FPI and hypoxemia than after FPI alone. In contrast, neuropathological changes were not evident following hypoxemia alone. These results show that, although hypoxemia alone was without effect, posttraumatic hypoxemia exacerbates FPI-induced reductions in visual discrimination accuracy and secondary hypoxemia interferes with control of the rat's choices by flicker frequency, perhaps in part as a result of neuronal loss and fiber degeneration in the dLG. These results additionally confirm the utility of this visual discrimination procedure as a sensitive, noninvasive means of assessing behavioral function after experimental traumatic brain injury.

Malaria poses a threat across several continents: Eurasia (Asia and parts of Eastern Europe), Africa, Central and South America. Bradley (1991) estimates human exposure at 2,073,000,000 with infection rates at 270,000,000, illnesses at 110,000,000, and deaths at 1,000,000. Significant mortality rates are attributed to infection by the parasite Plasmodium falciparum, with an estimated 90% among African children. A worldwide effort is ongoing to chemically and pharmacologically characterize a class of artemisinin compounds that might be promising antimalarial drugs. The U.S. Army is studying the efficacy and toxicity of several artemisinin semi-synthetic compounds: arteether, artemether, artelinic acid, and artesunate. The World Health Organization and the U.S. Army selected arteether for drug development and possible use in the emergency therapy of acute, severe malaria. Male Rhesus monkeys (Macaca mulatta) were administered different daily doses of arteether, or the vehicle alone (sesame oil), for a period of either 14 days, or 7 days. Neuropathological lesions were found in 14-day arteether treated monkeys in the precerebellar nuclei of the medulla oblongata, namely: (1) the lateral reticular nuclei (subnuclei magnocellularis, parvicellularis, and subtrigeminalis), (2) the paramedian reticular nuclei (subnuclei accessorius, dorsalis, and ventralis), and the perihypoglossal nuclei (n. intercalatus ofStaderini, n.of Roller, and n.prepositus hypoglossi). The data demonstrate that the simian medullary precerebellar nuclei have a high degree of vulnerability when arteether is given for 14 days at dose levels between 8 mg/kg per day and 24 mg/kg per day. The neurological consequences of this treatment regimen could profoundly impair posture, gait, and autonomic regulation, while eye movement disorders might also be anticipated.

Meconium aspiration in newborns causes lung inflammation and injury, which may lead to meconium aspiration syndrome (MAS). In this study, the effect of the antioxidant N-acetylcysteine on respiratory and inflammatory parameters were studied in a model of MAS. Oxygen-ventilated rabbits were intratracheally given 4 mL/kg of meconium (25 mg/mL) or saline. Thirty minutes later, meconium-instilled animals were administered N-acetylcysteine (10 mg/kg; i.v.), or were left without treatment. The animals were oxygen-ventilated for additional 5 h. Ventilatory pressures, oxygenation, right-to-left pulmonary shunts, and leukocyte count were measured. At the end of experiment, trachea and lung were excised. The left lung was saline-lavaged and a total and differential count of cells in bronchoalveolar lavage fluid (BAL) was determined. Right lung tissue strips were used for detection of lung edema (expressed as wet/dry weight ratio) and peroxidation (expressed by thiobarbituric acid-reactive substances, TBARS). In lung and tracheal strips, airway reactivity to acetylcholine was measured. In addition, TBARS and total antioxidant status were determined in the plasma. Meconium instillation induced polymorphonuclear-derived inflammation and oxidative stress. N-acetylcysteine improved oxygenation, reduced lung edema, decreased polymorphonuclears in BAL fluid, and diminished peroxidation and meconium-induced airway hyperreactivity compared with untreated animals. In conclusion, N-acetylcysteine effectively improved lung functions in an animal model of MAS.

U suvremenom poslovanju i upravljanju poslovnim procesima standardizacija svih postupaka omogućava stvaranje do-datne vrijednosti, konkurentnosti i uspješnosti u poslovanju organizacije. U tom smislu primjena ključnih pokazatelja uspješnosti za upravljanje zaštitom zdravlja, sigurnošću na radu i zaštitom okoliša (HSE) pridonosi razvoju učinkovitih i djelotvornih modela upravljanja područjem HSE. U radu je prikazana analiza teorijskih postavki zaštite zdravlja, si-gurnosti na radu, zaštite okoliša te ključnih pokazatelja uspješnosti (KPI). KPI pomažu organizaciji definirati i mjeriti napredak prema postavljenim organizacijskim ciljevima. Za učinkovito mjerenje KPI neophodno je postavljanje poslov-nih ciljeva. Ciljevi poslovanja moraju biti specifični, mjerljivi, ostvarivi, svrsishodni i vremenski određeni. Na temelju provedene analize prepoznate su mogućnosti na osnovu kojih su određeni KPI za procese HSE. Praćenje i mjerenje KPI u području zaštite zdravlja, sigurnosti na radu i zaštite okoliša provodi se temeljem postavljenih ciljeva, a direktno u-tječe na poboljšanje učinkovitosti i djelotvornosti HSE. Obzirom da je područje HSE jedan od pokazatelja uspješnog po-slovanja organizacije, možemo konstatirati da utvrđivanje i mjerenje KPI u području zaštite zdravlja, sigurnosti na ra-du i zaštite okoliša pomaže u postizanju poslovnih ciljeva organizacije.

The effect of blast overpressure on visual system pathology was studied in 14 male Sprague-Dawley rats weighing 360-432 g. Blast overpressure was simulated using a compressed-air driven shock tube, with the aim of studying a range of overpressures causing sublethal injury. Neither control (unexposed) rats nor rats exposed to 83 kiloPascals (kPa) overpressure showed evidence of visual system pathology. Neurological injury to brain visual pathways was observed in male rats surviving blast overpressure exposures of 104-110 kPa and 129-173 kPa. Optic nerve fiber degeneration was ipsilateral to the blast pressure wave. The optic chiasm contained small numbers of degenerated fibers. Optic tract fiber degeneration was present bilaterally, but was predominantly ipsilateral. Optic tract fiber degeneration was followed to nuclear groups at the level of the midbrain, midbrain-diencephalic junction, and the thalamus where degenerated fibers arborized among the neurons of: (i) the superior colliculus, (ii) pretectal region, and (iii) the lateral geniculate body. The superior colliculus contained fiber degeneration localized principally to two superficial layers (i) the stratum opticum (layer III) and (ii) stratum cinereum (layer II). The pretectal area contained degenerated fibers which were widespread in (i) the nucleus of the optic tract, (ii) olivary pretectal nucleus, (iii) anterior pretectal nucleus, and (iv) the posterior pretectal nucleus. Degenerated fibers in the lateral geniculate body were not universally distributed. They appeared to arborize among neurons of the dorsal and ventral nuclei: the ventral lateral geniculate nucleus (parvocellular and magnocellular parts); and the dorsal lateral geniculate nucleus. The axonopathy observed in the central visual pathways and nuclei of the rat brain are consistent with the presence of blast overpressure induced injury to the retina. The orbital cavities of the human skull contain frontally-directed eyeballs for binocular vision. Humans looking directly into an oncoming blast wave place both eyes at risk. With bilateral visual system injury, neurological deficits may include loss or impairments of ocular movements, and of the pupillary and accommodation reflexes, retinal hemorrhages, scotomas, and general blindness. These findings suggest that the retina should be investigated for the presence of traumatic or ischemic cellular injury, hemorrhages, scotomas, and retinal detachment.

In allergic asthma, activated cells produce various substances including reactive oxygen species (ROS). As heterogenic pathophysiology of asthma results to different response to the therapy, testing novel interventions continues. Because of water-insolubility of some potentially beneficial drugs, dimethyl sulfoxide (DMSO) is often used as a solvent. Based on its antioxidant properties, this study evaluated effects of DMSO on mobilization of leukocytes into the lungs, and oxidation processes induced by ovalbumin (OVA)-sensitization in a guinea-pig model of allergic asthma. Guinea-pigs were divided into OVA-sensitized and naive animals. One group of OVA-sensitized animals and one group of naive animals were pretreated with 10% DMSO, the other two groups were given saline. After sacrificing animals, blood samples were taken and total antioxidant status (TAS) in the plasma was determined. Left lungs were saline-lavaged and differential leukocyte count in bronchoalveolar lavage fluid (BAL) was made. Right lung tissue was homogenized, TAS and products of lipid and protein oxidation were determined in the lung homogenate and in isolated mitochondria. OVA-sensitization increased total number of cells and percentages of eosinophils and neutrophils in BAL fluid; increased lipid and protein oxidation in the lung homogenate and mitochondria, and decreased TAS in the lungs and plasma compared with naive animals. However, no differences were observed in DMSO-instilled animals compared to controls. In conclusion, OVA-sensitization increased mobilization of leukocytes into the lungs and elevated production of ROS, accompanied by decrease in TAS. 10% DMSO had no effect on lipid and protein oxidation in a guinea-pig model of allergic asthma.

Artemisinin (qinghaosu) and several derivatives have been developed and are in use as antimalarial drugs but scant information is available regarding animal or human toxicity. Following a eight-day, multiple-dose, pharmacokinetic study of arteether (AE) (10 mg/kg/day [n = 6] and 20 mg/kg/day [n = 6]) in dogs, all high-dose animals displayed a progressive syndrome of clinical neurologic defects with progressive cardiorespiratory collapse and death in five of six animals. Neurologic findings included gait disturbances, loss of spinal and pain response reflexes, and prominent loss of brain stem and eye reflexes. Animals had prolongation of QT interval corrected for rate (QTc) on electrocardiograms (ECGs) with bizarre ST-T segment changes. Prominent neuropathic lesions were noted to be primarily limited to the pons and medulla. Similar lesions with dose-related severity were noted in eight other dogs studied in a second study with intramuscular (IM) administration of AE in sesame oil during a 28-day, dose-ranging study using 5, 10, 15, and 20 mg/kg/day. Injury, graded by a pathologist blinded to the dose group, showed a dose-related, region-specific injury in all animals that was most pronounced in the pons. Further studies in Sprague-Dawley rats using IM administration of AE and artemether (AM) at a dose of 12.5-50 mg/kg/day for 28 days confirmed the onset of a clinical neurologic syndrome with dose-related changes in body weight, activity, and seizure-like activity, stereotypic movement disorders, and ECG changes.(ABSTRACT TRUNCATED AT 250 WORDS)

On the surface of the SiO2 catalyst used in the ammoximation of cyclohexanone to cyclohexanone oxime in the gaseous phase the formation of the imine group (supposed precursor in the reaction) was found previously. The authors investigated the possibilities of the occurence of the imine group on Ti-silicalite used as catalyst in the same reaction when performed in liquid phase. The technique using Ti-silicalite (previously treated with H2O2) suspension in cyclohexanone, NH4OH or their 1∶1 mixture dried on an irtran disc gave the possibility of indicating the formation of surface adsorption complexes by IR spectroscopy. The appearance of a band at 1654 cm−1 corresponding to υ(C=N) after the adsorption of cyclohexanone together with NH4OH indicates the formation of the imine group, whereas the simultaneous lowering of the intensity of the band 970 cm−1 (Ti-O vibration) indicates that the Ti centres take part in this process.

Background: Microalbuminuria reflects a state of widespread vascular dysfunction, whereas obstructive sleep apnea (OSA) further promotes atherosclerotic damage in hypertension. Study Design: Cross-sectional. Setting & Participants: In an outpatient hypertensive unit, 62 untreated hypertensive patients (aged 48 ± 7 years; office blood pressure [BP], 151 ± 8/97 ± 7 mm Hg) with OSA and 70 hypertensive patients without OSA (apnea hypopnea index [AHI] ≤ 5) matched for age, sex, smoking status, body mass index, and 24-hour pulse pressure were studied. Predictor Variable: Hypertension and OSA compared with hypertension without OSA. OSA defined as AHI greater than 5, documented by polysomnography. Outcome Variable: Albuminuria assessed by urinary albumin-creatinine ratio (ACR). Measurements: Participants underwent polysomnography, ambulatory BP monitoring, echocardiography, routine metabolic profile assessment, and glomerular filtration rate estimation, whereas ACR was measured from 2 nonconsecutive morning spot urine samples. Results: Hypertensive patients with OSA compared with those without OSA showed increased 24-hour diastolic BP (87 ± 7 versus 85 ± 7 mm Hg; P = 0.03) and nighttime pulse pressure (50 ± 10 versus 45 ± 10 mm Hg; P = 0.008), but did not differ regarding metabolic profile and estimated glomerular filtration rate. Albuminuria was greater by 57% in patients with OSA compared with those without OSA: log(10)ACR, 1.1 ± 0.2 versus 0.7 ± 0.4 mg/g; P < 0.001). In the entire study population, log10(ACR) correlated with log10(AHI) (r = 0.35; P < 0.001), minimum oxygen saturation during sleep (r = -0.33; P < 0.001), 24-hour pulse pressure (r = 0.38; P < 0.001), and nighttime pulse pressure (r = 0.21; P =0 .01). In a multivariable linear regression model, independent predictors of ACR were AHI (β = 0.36; P < 0.001) and 24-hour pulse pressure (β = 0.25; P = 0.01). Limitations: Cross-sectional study. Conclusions: Albuminuria increases within the normal range in hypertensive individuals with OSA compared with those without OSA proportionally to OSA severity independently of confounders. The association of upper-airway dysfunction with albuminuria and pulsatile hemodynamic load may provide an explanatory mechanism for the OSA-related risk in hypertension. © 2008 National Kidney Foundation, Inc.

A general framework based on a 4-port, 2-layer circuit model has been developed to describe surface wave propagation in periodic surfaces. For the specific case of high impedance surfaces, a new mechanism for the occurrence of electromagnetic band gaps is presented based on eigenmode analysis. It is shown that the eigenmode of a surface electromagnetic wave at any given frequency can be written as a linear combination of two "pure" modes: a backward wave mode that propagates primarily within the surface, and a forward wave mode that resides primarily on the surface. At the band gap frequencies, the two pure modes couple so as to result in no propagation. It is anticipated that the circuit model developed as part of this work will be a powerful tool fore understanding and exploration of a large class of periodic systems.

A broadband scalable lumped-element model for multiport transformers integrated on a silicon substrate is presented. The model is based on a pi-T network for the primary and secondary coils and utilizes only frequency-independent elements to model the frequency-dependent resistive losses. Four-port S-parameters are measured for multiport transformers up to 15 GHz and accurate compact models extracted up to 4 GHz, which covers the fundamental frequency bands and their second harmonics of interest for European and US GSM/EGSM and DCS/PCS cellular bands. Good agreement is obtained between modeled and measured transformer performance attributes.

We summarize several de-embedding techniques and propose an approach using a 2-impedance model, which has one shunt and one series impedance that gives consistent results when applied to three different lengths of microstrip. We also discuss results on microstrip lines having a ground metal thickness less than a skin depth, and show the impact of the layers below thin grounds on simulations. Very good agreement is obtained between simulated and de-embedded measured results.

This paper presents a systematic analysis of inductors on silicon by using EM simulation on a FEM (finite element method) based simulator. First, the EM simulation capability is established by achieving a good agreement with measured data in terms of S-parameters, quality factor, and effective inductance. Then, both the geometrical parameters such as inner diameter and number of turns and process parameters such as metal thickness and metal conductivity are varied to determine the impact on inductor performance. Also, different shapes of inductors, octagonal and square, are simulated to compare the performance. The use of ground ring is investigated to see the effect. The analysis provides a comprehensive guideline for designing and optimizing on-chip inductors on silicon.

New compact model forms for two-port and three-port symmetric inductors fabricated on silicon are discussed in this paper. These new models incorporate a frequency independent RL network that mimics the skin effect behavior of transmission lines on conductive substrates and can accurately predict the inductive behavior as well as the one-port single-ended and the one-port differential Q of these devices at microwave and millimeter wave frequencies. The new models are validated on inductors fabricated in a thick plated copper process.

Electrical performances of 4-port n:n dual-spiral transformers fabricated in a thick plated copper on silicon process are analyzed. Multiport data analysis techniques and compact modeling are used to study the relationships between the physical and the electrical attributes of the devices. Analytical models, based on measurements from 50 MHz to 20 GHz, are used to explore achievable device performance under different design constraints.

Chip scale packages (CSP) are entering large-scale production in applications such as portable computers and consumer products. In such applications, size and weight reduction is a key goal. However, because the bulk of present and near-term CSP applications are cost-sensitive, these size and weight reductions can not come at a premium cost. The CSP producer is faced with a multi-faceted challenge. State-of-the-art process, equipment and materials are required to build these packages, but little to no price increase is acceptable. By their nature, CSPs contain minimal material to provide mechanical and environmental protection to the semiconductor die, yet no reliability performance relief is granted to CSPs. In this paper, the efforts to meet the CSP metrics of low size and weight, low cost, and high reliability for a flip-chip BGA package (the SLICC, or Slightly Larger than IC Carrier) are presented. For this package, the key challenge was to improve reliability from the then-present unacceptable level to meet Motorola package reliability requirements, without causing an unacceptable penalty in cost or manufacturability. The package construction and assembly are reviewed. Project success metrics are presented. The rational, planning, execution and analysis of a series of designed experiment performed to improve manufacturability and/or reliability are explained. The success of efforts in meeting cost and manufacturability metrics while exceeding reliability metrics is described.

RF modules are building blocks for future wireless communication products. A process that combines electromagnetic (EM) simulation with measurement data provides a means to develop circuit simulation libraries for embedded passive components in low temperature cofired ceramic (LTCC) substrates.

High precision metal-insulator-metal capacitors with a capacitance density of 1.6 fF/um/sup 2/ and metal thin film resistors of 50 ohm/sq. sheet resistance and a negative temperature coefficient of resistivity smaller than 100 ppm//spl deg/C have been integrated in a dual-inlaid Cu-based backend for mixed-signal applications. These devices deliver reduced parasitics, better linearity, lower temperature coefficients, lower noise, and better matching as compared to current silicon based devices.

Transformers integrated onto silicon substrates are characterized using a four-port network analyzer. S-parameters measured up to 20 GHz are used to study the trade-off between the device dimensions and the electrical performance of typical n:n transformers. A second order four-port compact model for integrated transformers is proposed. The evaluation of this model on devices in both standard four-port and two-port differential-to-differential configurations show a magnitude accuracy better than 8 % and a phase error less than 5 degrees in the frequency range from 300 MHz to 3 GHz.

In a previous study, we demonstrated that tadpoles are suitable organisms for monitoring small bodies of water (e.g., creeks, ponds, and drainage ditches) for genotoxicity using the alkaline single-cell gel DNA electrophoresis (SCG) or "comet" assay [Ralph and Petras, 1997]. This approach involves detection, under alkaline conditions, of cell DNA fragments which on electrophoresis migrate from the nuclear core, resulting in a "comet with tail" formation. In this initial study, most of the tadpoles collected were in the early stages of larval development, but this is not always possible. The present study evaluated the sensitivity of tadpoles, at different stages of larval development, to a range of concentrations of the genotoxicant methyl methane-sulphonate (MMS). Four specific phases of Rana clamitans (green frog) larval development were examined: first-year limbless tadpoles (Stage I as defined by Taylor and Kollros [1946]), second-year limbless tadpoles (Stages II-III), second-year tadpoles with only hindlimbs (Stages X-XVIII), and second-year tadpoles with all four limbs evident and a tail undergoing resorption (Stages XXII-XXIII). Twenty-four hour exposures to MMS of tadpoles in the three earliest phases produced a significant (P0.01) added variance component among tadpoles for DNA damage and there were significant increases (P0.05) in the length:width ratios of the DNA patterns at concentrations as low as 1.56 mg/I. However, tadpoles in the last phase studied (both pairs of limbs present) showed no significant (P0.05) added variance component and no significant increases (P0.05) in DNA damage upon exposure to any of the MMS doses tested. A nested ANOVA indicated that, for each of the tested concentrations of MMS, but not the dechlorinated water control, there was significant heterogeneity (P0.05) in DNA damage when tadpoles of all four phases studied were compared. However, when tadpoles of the lost phase of development were removed from the comparison, there was no significant heterogeneity (P0.05) among tadpoles of the remaining three phases. Possible reasons for this insensitivity to MMS as animals enter the metamorphic climax were considered. The results indicate that pooling of the early tadpole phases of R. clamitans for SCG environmental genotoxicity biomonitoring is acceptable.

Exposure to blast overpressure can typically inflict generalized damage on major organ systems, especially gas-containing organs such as the lungs and the gastrointestinal tract. The purpose of the present study was to use rat's food intake and exercise wheel running as behavioral correlates of the perhaps more subtle damage to these organ systems induced by sublethal blast overpressure. Toward this end, all rats were exposed to a 12-h light/dark cycle and food was available only in the dark period. Prior to exposure, rats in the (E)xercise group were required to execute five rotations of an activity wheel for a food pellet; wheel turns that occurred at times other than when a rat was feeding were recorded separately and labeled exercise running. In the (S)edentary and (A)nesthesia groups, wheel running was not possible and rats were required to execute five leverpresses for a single pellet. A compressed air-driven shock tube was used to expose rats to a supra-atmospheric wave of air pressure. The tube was separated into two sections by a polyester membrane, the thickness of which determined peak and duration of overpressure. All rats were anesthetized with 50 mg/kg of phenobarbital. After reaching a deep plane of anesthesia, they were individually tied in a stockinet across one end of the shock tube. In preliminary tests, the membrane thickness was 1000 (A)ngstroms and rats in Group L(ethality) were exposed to a 129 kPa (peak amplitude) wave of overpressure. Three of six rats survived exposure to this peak pressure; pathology was evident in the lungs and gastrointestinal tract of all non-survivors. Rats in Groups E and S were tested with a 500Amembrane, which resulted in an 83 kPa peak amplitude. All rats survived exposure to this lower peak pressure. On the day of exposure to blast, the relative reduction of intake during the first 3 h of the dark period was significantly greater for Group E than for Groups S and A; the intake of Groups E and S remained reduced for four additional recovery days. Bodyweight was not significantly affected. Exercise wheel running also was reduced significantly on the day of exposure and during subsequent recovery days. These preliminary findings suggest that exposure to sublethal blast overpressure can reduce food consumption and exercise performance, perhaps as a consequence of damage to the gastrointestinal tract and lungs.

Pesticides are broadly used for pest control in agriculture despite possible negative impacts they may pose to the environment. Thus, we examined the DNA damage caused by five herbicides commonly used in southern Ontario (Canada). Erythrocytes from Rana catesbeiana (bullfrog) tadpoles were evaluated for DNA damage following exposure to selected herbicides, using the alkaline single-cell gel DNA electrophoresis (SCG) or "comet" assay [Singh et al. (1988): Exp Cell Res 175:184-191; Ralph et al. (1996): Eviron Mol Mutagen 28:112-120]. This approach involves detection, under alkaline conditions, of DNA fragments that upon electrophoresis migrate from the nuclear care, resulting in a comet formation. The herbicides tested, along with their active ingredients, were AAtrex Nine-O (atrazine), Dual-960E (metalochlor), Roundup (glyphosate), Sencor-500F (metribuzin), and Amsol (2,4-D amine). Tadpoles were exposed in the laboratory for a 24-hr period to several concentrations of the herbicides dissolved in dechlorinated water. Methyl methanesulphonate was used as a positive control. The herbicides AAtrex Nine-O-, Dual-960E-, Roundup-, and Sencor-500F-treated tadpoles showed significant DNA damage when compared with unexposed control animals, whereas, Amsol-treated tadpoles did not. Unlike the other responding herbicides, Sencor-500F did not show a relationship between dosage and DNA damage. In summary, the results indicate that at least some of the herbicides currently used in southern Ontario are capable of inducing DNA damage in tadpoles.

To monitor genotoxicity in small bodies of water (e.g., creeks, ponds, and drainage ditches) we examined tadpole erythrocytes of two species: Rana clamitans and Rana pipiens,using the alkaline single cell gel DNA electrophoresis (SCG) or "comet" assay. This approach involves detection, under alkaline conditions, of cell DNA fragments which on electrophoresis migrate from the nuclear core, resulting in a "comet with tail" formation. Fifty-six samples, a total of 606 tadpoles, from 18 sites in southern Ontario, collected between 1993 and 1995, were examined. Samples of R. clamitans tadpoles collected in 1994 and 1995, from regions with heavy agricultural activity, gave significantly higher (P0.001) DNA length to width ratios than samples of R. clamitans tadpoles collected from sites in the Bruce Peninsula and near the French River, which have little or no agriculture. Samples of R. pipiens tadpoles collected in 1994 from sites on the outskirts of Windsor, Ontario, sites which receive genotoxic inputs from nearby industries, gave significantly higher (P0.001) DNA ratios than samples from agricultural areas and the Bruce Peninsula. R. clamitans tadpoles showed significant annual variation in DNA damage which was greater in samples of tadpoles collected from agricultural areas than from the Bruce Peninsula. The higher levels of DNA damage in tadpoles collected from agricultural areas may be due to the pesticides used, and the increased variation in DNA damage in the same areas is likely due to the impact of crop rotation, including leaving fields fallow, the timing of rainfall, and/or the application of pesticides. R. clamitans tadpoles, especially those collected from agricultural areas, also showed significant seasonal variation in DNA damage. There was no significant (P0.05) seasonal or annual variation in the levels of DNA damage in R. pipiens tadpoles collected from the Tallgrass Prairie. This study indicates that both species are suitable for use in the alkaline SCG assay and as in situ sentinel organisms for environmental biomonitoring.

Small bodies of water (e.g., creeks, ponds, and drainage ditches) have received very little attention in genotoxicity studies, yet these areas are important because they are often the first to be affected by industrial effluents, sewage contaminants, accidental spills, internal combustion engine emissions, landfill runoffs, and pesticide uses. To address this deficiency, we examined erythrocytes in two species of tadpoles, Rana clamitans and Bufo americanus, using the alkaline single-cell gel (SCG) ("comet") assay. This approach involves detection, under alkaline conditions, of cell DNA fragments, which on electrophoresis migrate from the nuclear core, resulting in a "comet-with-tail" formation. Exposure of R. clamitans todpoles to a range of concentrations of methyl methanesulfonate (MMS) produced a linear increase in DNA length to DNA core width ratios. This is consistent with findings in a number of other species. Time-dose experiments using MMS suggest that the peak level of DNA damage in R. clamitans todpoles occurred 42 hr after exposure. B. americanus tadpoles exposed to 6.25 mg/l of MMS for 12 hours had a significant increase in DNA damage over that seen in the controls. Freshly caught R. clamitans tadpoles from Highgate and B. americanus tadpoles from Duart, both on the north shore of Lake Erie, gave ratios of 2.78 and 2.07, respectively. This region of Ontario is a prime agricultural area and pesticide use is extensive. Tadpoles from Highgate and Duart, maintained in the laboratory for 4 months and 6 weeks, respectively, gave ratios of 1.29 and 1.44. The results of the SCG procedure in tadpoles indicate that this assay is extremely sensitive and suitable for detecting genotoxicity in the environment.

The alkaline single-cell gel (SCG) assay, which determines DNA damage in mice treated with 100 mg/kg methyl methanesulfonate (MMS), was run by using three power supplies from Bio-Rad (models 3000Xi, 200/2.0, and Power Pac 300). Comparisons of the results obtained from the use of these power supplies showed differences in mean DNA tail length to width ratios and profiles of these ratios in individual cells. Model 200/2.0 power supply appeared to enhance significantly the sensitivity of the assay. In purchasing power supplies, there is a need to evaluate their effect on the sensitivity of the test.

Battlefield use of nerve agents poses serious medical threats to combat troops and to civilians in the immediate or adjacent environment. The experiments reported herein were carried out in the 1980s to help to define both the neurological and neuropathological consequences of exposure to the organophosphate nerve agent Soman. These data contributed to the scientific foundation for a program of drug development to find agents that would prevent or reduce the risk of injury to the central nervous system and specifically pointed to the importance of including an anticonvulsant in the treatment of agent exposure. Since these experiments were conducted, research efforts have continued to improve pretreatment and treatment, such as the inclusion of the anticonvulsant diazepam in the medical treatment of exposed personnel.

A solid-solid interaction between Cu oxides and NH 4 -Y or HZSM-5 zeolite was investigated by means of IR, ESR, XPS, SEM and development of the catalytic activity. It is shown that Cu ions from the metal oxide are incorporated into the zeolite cationic sites. The process is controlled by temperature, Cu oxide content and, it is enhanced by water or ammonia presence. Moreover, it can be applied as a method for preparation of highly active Cu-zeolite based catalyst for selective reduction of NO with ammonia at low (470 K) temperature.

The sensory innervation of the postpharyngeal foregut was investigated by injecting the enzyme horseradish peroxidase (HRP) into the walls of the esophagus, stomach, or duodenum. The transported HRP was identified histochemically, labeled neurons in the spinal and vagal ganglia were counted, and the results were plotted using an SAS statistical program. The spinal sensory fields of each viscus were defined using three determinations: craniocaudal extent, principal innervation field, and peak innervation field. The data revealed that innervation fields are craniocaudally extensive, the sensory field of each viscus overlaps significantly with its neighbor, yet each viscus can be characterized by a field of peak innervation density. Craniocaudal innervation of the esophagus spans as many as 22-23 paired spinal ganglia (C1-L2). There are two peak innervation fields for the cervical (C2-C6 and T2-T4) and for the thoracic (T2-T4 and T8-T12) sectors of the esophagus. The sensory innervation of the stomach extends craniocaudally over as many as 25 paired spinal ganglia (C2-L5). The peak innervation field of the stomach spans a large area comprising the cranial, middle, and the immediately adjoining caudal thoracic ganglia (T2-T10). The duodenum is innervated craniocaudally by as many as 15 paired thoracolumbar ganglia (T2-L3). Peak innervation originates in the middle and caudal thoracic ganglia and cranial lumbar (T6-L1) ganglia. There is a recognizable viscerotopic organization in the sensory innervation of the postpharyngeal foregut; successively more caudal sectors of this region of the alimentary canal are supplied with sensory fibers from successively more caudal spinal dorsal root ganglia. Vagal afferent innervation of the esophagus, stomach, and duodenum is bilateral and originates predominantly, but not exclusively, from vast numbers of neurons in the nodose (distal) ganglia. The esophagus is innervated bilaterally and more abundantly by jugular (proximal) ganglia neurons than is either the stomach or duodenum. The physiological significance of the findings are discussed in relation to the phenomena of visceral pain and referred pain.

Documentation typically is an area that can be streamlined, thereby saving nursing time and money. The authors' nursing division created a combination intervention record and nursing progress notes form for a 24-hour period. The results yielded a savings of 90 minutes of RN time in a 24-hours period, a 36% reduction in charting time, and an annual cost savings of $437,000.

Documentation typically is an area that can be streamlined, thereby saving nursing time and money. The authors' nursing division created a combination intervention record and nursing progress notes form for a 24-hour period. The results yielded a savings of 90 minutes of RN time in a 24-hours period, a 36% reduction in charting time, and an annual cost savings of $437,000.

The origin of spinocerebellar projections from the caudal cervical, the thoracic, and the cranial lumbar regions of the spinal cord was studied in neonatal dogs. The present cytoarchitectonic and experimental studies of the cervical intumescence of the spinal cord led to the description of a cell group prominent in the dorsal horn, the nucleus centrobasalis. This nucleus, comprised of neurons of varying size and shape, extended over the length of the cervical intumescence. The largest neurons of the n. centrobasah exhibited retrograde reaction following cerebellar injury or they accumulated horseradish peroxidase (HRP) after injection of the enzyme into the cerebellum. Unilateral cerebellar ablation or cordotomy evoked retrograde changes in the ipsilateral nucleus. The cerebellar-projecting neurons were large, multipolar and chromatophilic. They occured singly, in small clusters, or in columns. The columnar arrangement was common at caudal levels of the cervical intumescence where these large cells were most abundant. The results of earlier experiments with cats and rhesus monkeys have demonstrated massive fiber degeneration in the n. centrobasah following dorsal rhizotomy (Petras, '65, '66; Petras and Cummings, '72). The presence of spinal afferents in this nucleus suggests that its largest neurons may serve as a link for the passage of forelimb afferent information to the cerebellum by way of an uncrossed brachiospinocerebellar projection. The present anatomical data suggest too that these large neurons are the cells of origin for the rostral spinocerebellar tract (Oscarsson and Uddenberg, '64; Oscarsson, '65). The cellular composition of the nucleus dorsalis was studied also, and the results compared with Loewy's ('70) findings in the cat. Three types of neurons were present in the n. dorsalis. These have been classified as giant, medium, and small-sized neurons. The giant and medium-sized neurons responded to cerebellectomy, and accumulated enzyme following HRP injections into the cerebellum. The retrograde responses, generally, were most pronounced in cranial thoracic segments and diminished progressively in more caudal segments. Unilateral cerebellar ablations, cerebellar pedunculotomy, and cordotomy almost exclusively affected ipsilateral neurons. The present study provides the first demonstration of discrete retrograde changes in the giant cells of Clarke's column following cerebellectomy. The contribution of the medium-sized neurons of the n. dorsalis to spinocerebellar projections is established for the first time.

The origin of spinocerebellar projections from the cranial cervi cal spinal cord was studied in neonatal dogs following cerebellar ablations or the injection of horseradish peroxidase (HRP) into the cerebellum. Cerebellar ablations produced distinct retrograde changes of three types: type I response or cen tral chromatolysis; type II response or ghost cells; and type 111 response or neu ronal loss and gliosis. These ablation-induced changes were evident in the cells of the nucleus cervicalis centralis. The results of hemicerebellectomy, unilateral cer ebellar pedunculotomy, and cordotomy established that the cells of this nucleus project contralaterally to the cerebellum. Cytoarchitectonic study revealed that this nucleus is composed of clustered medium-sized, multipolar, chromatophilic neurons located in the zona intermedia of the C1-C4 segments. The retrograde la beling of central cervical neurons following cerebellar injections of HRP con firmed the results obtained with the axonal reaction. Anterograde fiber degeneration was present in the central cervical nucleus following dorsal rhizotomy in the dog and cat. These experiments demonstrated dorsal root fibers among the somata of central cervical neurons rendered chromatolytic following cerebellectomy in the dog. Electron microscopic evidence is presented for the presence of degenerated dorsal root terminals upon the dendrites and somata of central cervical neurons. The nucleus cervicalis centralis forms a direct link between neck afferents and the cerebellum by way of a crossed cervicospinocerebellar pathway. Evidence could not be found for the presence of a spinocerebellar projection originating in the nucleus ceruicalis lateralis.

The kappa opioid agonist dynorphin A (Dyn A) (1-13) produced dose-related neurological deficits after subarachnoid injection in the lumbar spinal cords of rats. Whereas the neurological dysfunctions produced by low doses of Dyn A (1-13) were transient, higher doses caused persistent deficits, characterized by motor and nociceptive impairment in hindlimbs and tail, hindlimb edema, priapism, bladder infarction and atony and urinary incontinence. These deficits appeared to result from nonopioid actions of Dyn A (1-13), as they were: 1) not blocked by the opioid antagonists naloxone or WIN 44,441-3; 2) shared by Dyn A (3-13), which lacks opioid activity; and 3) not produced or altered by the selective kappa opioid agonist U 50,488. Coinjection of a combination of peptidase inhibitors, shown previously to enhance the actions of Dyn A fragments in vitro, significantly increased the paralytic actions of Dyn A (1-13). The peptidase inhibitors did not by themselves cause neurological dysfunction, and they did not alter the paralytic potency of the peptidase-resistant delta opioid antagonist ICI 174864. These findings indicate that Dyn A effects were: 1) limited appreciably by its rapid enzymatic degradation after injection and 2) most likely the result of actions of the intact peptide rather than proteolytic products generated after injection. Neuroanatomical evaluations revealed extensive neuronal and axonal injury in the lumbosacral spinal cords of rats injected with 25 nmol of Dyn A (1-13). Collectively, these results indicate that Dyn A (1-13) acts through nonopioid mechanisms to cause the injury and death of neurons involved in diverse spinal cord functions.