Chronic ethanol induces a pro-inflammatory switch in interleukin-1ß regulation of GABAergic signaling in the medial prefrontal cortex of male mice.

Neuroimmune pathways regulate brain function to influence complex behavior and play a role in several neuropsychiatric diseases, including alcohol use disorder (AUD). In particular, the interleukin-1 (IL-1) system has emerged as a key regulator of the brain's response to ethanol (alcohol). Here we investigated the mechanisms underlying ethanol-induced neuroadaptation of IL-1ß signaling at GABAergic synapses in the prelimbic region of the medial prefrontal cortex (mPFC), an area responsible for integrating contextual information to mediate conflicting motivational drives. We exposed C57BL/6J male mice to the chronic intermittent ethanol vapor-2 bottle choice paradigm (CIE-2BC) to induce ethanol dependence, and conducted ex vivo electrophysiology and molecular analyses. We found that the IL-1 system regulates basal mPFC function through its actions at inhibitory synapses on prelimbic layer 2/3 pyramidal neurons. IL-1ß can selectively recruit either neuroprotective (PI3K/Akt) or pro-inflammatory (MyD88/p38 MAPK) mechanisms to produce opposing synaptic effects. In ethanol naïve conditions, there was a strong PI3K/Akt bias leading to a disinhibition of pyramidal neurons. Ethanol dependence produced opposite IL-1 effects - enhanced local inhibition via a switch in IL-1ß signaling to the canonical pro-inflammatory MyD88 pathway. Ethanol dependence also increased cellular IL-1ß in the mPFC, while decreasing expression of downstream effectors (Akt, p38 MAPK). Thus, IL-1ß may represent a key neural substrate in ethanol-induced cortical dysfunction. As the IL-1 receptor antagonist (kineret) is already FDA-approved for other diseases, this work underscores the high therapeutic potential of IL-1 signaling/neuroimmune-based treatments for AUD.

[Study protocol of the monocentric prospective randomized placebo-controlled double-blind phase II study to explore the protective effects of the ginkgo biloba extract EGb 761® from temporary noise-induced hearing loss]. / Prüfplan für die monozentrische prospektive randomisierte placebokontrollierte doppelblinde Phase-II-Studie zur Exploration protektiver Effekte des Ginkgo-biloba-Spezialextrakts EGb 761® vor einer vorübergehenden Hörschädigung durch Lärm.

BACKGROUND: Hearing loss is frequently induced by occupational noise exposure and leads to rising hearing thresholds as well as reduced otoacoustic emissions (OAE), mostly caused by metabolic hair cell decompensation. OBJECTIVE: Primary endpoint is the increase in average pure tone thresholds after noise exposure, secondary endpoints are loss of distortion product and click-evoked OAE as well as reduction of their contralateral suppression. PARTICIPANTS AND METHODS: The present study design describes the verification of the anti-oxidant and neuroprotective properties of EGb 761® by evaluation of cochlear protection from noise impact as well as its safety and tolerance in 202 healthy male participants distributed equally to verum and placebo groups in a double-blind manner. Participants were assessed, medicated, exposed to noise, and then examined at timepoints up to 10 min and 4 weeks thereafter. CONCLUSION: This summary of the verification study protocol highlights the complexity of diligent and precise planning according to the European Medicines Agency criteria for controlled trials (EudraCT). Key points are the intervention rationale, definitions of in- and exclusion criteria, estimation of subject numbers, and examination method setting in terms of optimum endpoint description.

Intermittent tinnitus-an empirical description.

BACKGROUND: Tinnitus is often classified into acute or chronic persistent forms. However, epidemiologic studies have shown that intermittent tinnitus (IT), which does not clearly belong to either category, is the most common form. OBJECTIVE: The aim of this study was to further characterize IT empirically. MATERIALS AND METHODS: We conducted an exploratory cross-sectional interview study among 320 subjects with tinnitus. Sociodemographic and tinnitus characteristics, concomitant complaints, perceived triggers, and help-seeking behavior were assessed. Subjects were classified into continuous (CT), IT, or single-episode tinnitus (SET) if they had experienced tinnitus "continuously," "temporarily time and again," or "only once but for several days," respectively, during the past 12 months. RESULTS: Of the sample, 62% reported IT, 23% SET, and 16% CT. Mean time since onset was 36 (CT), 28 (IT), and 19 months (SET), respectively. Most subjects with IT experienced episodes lasting a few days, whereas in 25%, episodes lasted 1-4 weeks. Mean duration was 1.6 weeks. The frequency of IT episodes ranged from every few days to half-yearly; mean frequency was every 7 weeks. Leading triggers were occupational and private stress. Asthenia, depression, social isolation, psychiatric disorders, and inner ear disorders were more prevalent among CT than IT subjects. Help-seeking behavior was comparable between CT and IT. CONCLUSION: IT is associated with emotional reactions and situational impairment severe enough to trigger multiple treatment attempts, but usually does not result in severe impairment. Inner ear disorders and psychological changes are less frequent than in CT; therefore, treatment response and prognosis might be better. We suggest classification of tinnitus into acute single-episode (<3 months), intermittent, or chronic persistent (>3 months) forms.

[Intermittent tinnitus-an empirical description. German version]. / Intermittierender Tinnitus ­ eine empirische Beschreibung.

BACKGROUND: Tinnitus is often classified into acute or chronic persistent forms. However, epidemiologic studies have shown that intermittent tinnitus (IT), which does not clearly belong to either category, is the most common form. OBJECTIVE: The aim of this study was to further characterize IT empirically. MATERIALS AND METHODS: We conducted an exploratory cross-sectional interview study among 320 subjects with tinnitus. Sociodemographic and tinnitus characteristics, concomitant complaints, perceived triggers, and help-seeking behavior were assessed. Subjects were classified into continuous (CT), IT, or single-episode tinnitus (SET) if they had experienced tinnitus "continuously," "temporarily time and again," or "only once but for several days," respectively, during the past 12 months. RESULTS: Of the sample, 62% reported IT, 23% SET, and 16% CT. Mean time since onset was 36 (CT), 28 (IT), and 19 months (SET), respectively. Most subjects with IT experienced episodes lasting a few days, whereas in 25%, episodes lasted 1-4 weeks. Mean duration was 1.6 weeks. The frequency of IT episodes ranged from every few days to half-yearly; mean frequency was every 7 weeks. Leading triggers were occupational and private stress. Asthenia, depression, social isolation, psychiatric disorders, and inner ear disorders were more prevalent among CT than IT subjects. Help-seeking behavior was comparable between CT and IT. CONCLUSION: IT is associated with emotional reactions and situational impairment severe enough to trigger multiple treatment attempts, but usually does not result in severe impairment. Inner ear disorders and psychological changes are less frequent than in CT; therefore, treatment response and prognosis might be better. We suggest classification of tinnitus into acute single-episode (<3 months), intermittent, or chronic persistent (>3 months) forms.

[Influence of medical BPS treatment on sexual function]. / Einfluss medikamentöser BPS-Therapie auf die sexuelle Funktion.

BACKGROUND: Benign prostate syndrome is frequently associated with sexual dysfunction. The therapeutic options discussed in the S2e guideline may be able to improve existing sexual dysfunctions but can also worsen disorders or even trigger new ones. OBJECTIVES: What are the effects of therapeutic options as described in the S2e guideline on sexual function? METHODS: By selective literature search related to benign prostate syndrome and sexual dysfunction adverse effects of drugs mentioned in the S2e guideline have been evaluated. RESULTS: Serenoa repens extracts do not have adverse effects on sexual function; this is also true for muscarine receptor antagonists. 5α-Reductase inhibitors frequently worsen erectile function, libido and ejaculation; selective α1-blockers have an adverse effect on ejaculation. Phosphodiesterase (PDE)-5 inhibitors can improve sexual function. A combination of α1-blockers and 5α-reductase inhibitors worsens sexual functions significantly. CONCLUSIONS: A suitable therapy for benign prostate syndrome should be chosen jointly by the patient and the treating physician and should be adapted to personal needs. Effects on sexual functions have to be taken into consideration when choosing a therapy.

Chemoenzymatic synthesis and utilization of a SAM analog with an isomorphic nucleobase.

SalL, an enzyme that catalyzes the synthesis of SAM from l-methionine and 5'-chloro-5'-deoxyoadenosine, is shown to accept 5'-chloro-5'-deoxythienoadenosine as a substrate and facilitate the synthesis of a synthetic SAM analog with an unnatural nucleobase. This synthetic cofactor is demonstrated to replace SAM in the DNA methylation reaction with M.TaqI.

No benefit adding eleutherococcus senticosus to stress management training in stress-related fatigue/weakness, impaired work or concentration, a randomized controlled study.

INTRODUCTION: Plant adaptogens are traditionally used for stress-related symptoms, but clinical evidence is inconsistent. This trial explored the effects of 120 mg/day Eleutherococcus senticosus root extract (ES), 2-day professional stress management training (SMT) and a combination of both (COM). METHODS: 144 participants suffering from asthenia and reduced working capacity related to chronic stress were randomized to the treatments. Validated scales and tests were used to investigate cognitive performance; feeling stressed; fatigue and exhaustion; alertness, restlessness and mood; quality of life and sleep; physical complaints and activities; and physiological stress parameters including cortisol awakening response (CAR), at baseline, after 2 and 8 weeks of treatment (German Clinical Trials Register DRKS00000692). RESULTS: Almost all parameters improved significantly over time without group differences. Significant differences were found in mental fatigue and restlessness, both in favor of COM vs. ES. COM was not superior to SMT in any parameter at week 8. An attenuation of the CAR was seen at week 2 without group differences. All treatments were well tolerated. DISCUSSION: Effects of adding ES to SMT are, if any, negligible.

[Use of St. John's Wort for depression in primary care - a non-interventional study]. / Stellenwert von Johanniskraut- extrakt in der hausärztlichen Depressionstherapie. Eine nicht interventionelle Studie.

BACKGROUND: Mild to moderate depression is frequently treated by general practitioners in Germany, quite often with St. John's Wort preparations. In contrast, controlled clinical trials were usually performed in psychiatric specialist centers or hospitals. METHODS: In this one-armed, prospective non-interventional study 408 general practitioners documented 1300 patients with mild or moderate depression, which received 600 mg St. John's Wort extract WS 5570 once daily. The observation period was 8 to 10 weeks. Therapeuticeffectand tolerabilityof WS 5570 were investigated. Additionally, doctors were asked for their experienceswith and attitudes to depression therapy and complementary medicine, reasons for administration of St. Johns Wort and its contribution totreatmentsuccess. RESULTS: 807 patients, who were included in the analysis corresponding to the protocol, had rates for successful treatment (> 50% decrease of the Hamilton 17-item depression scale [HAMD]) 79,3%, respectively for remission 68,4%. Six patients (0.46%) dropped out for adverse drug reactions. For comparison with the results of an earlier controlled clinical study (WS 5570 600 mg/d vs. 1200 mg/d vs. placebo), which was conducted mainly by medical specialists, 257 patients complying with the inclusion criteria of the controlled study were analysed. HAMD-scores at entry (22.9) and improvement after 2 (-6.6) and 6 weeks (-10.8) were very similar to those reported in the controlled clinical trial. 202 evaluable questionnaires completed by 408 doctors were available. Doctors regarded self-healing and placebo effects as important therapeuticfactors; however, in 75% of the cases they assigned at least 50% of treatment success to the St. John's Wort preparation, and in 19% it was regarded as the only reason for improvement. CONCLUSIONS: General practitioners consider St. John's Wort extract WS 5570 a well tolerable therapeutic instrument contributing more than 50% to total treatment effect. Causal conclusions to the efficacy of WS 5570 cannot be drawn in this study because of the non-interventional design. Efficacy of treatment of mild to moderate depression in primary care is comparable to findings in specialist-based controlled clinical studies.

Symptomatic and quality of life response to tolterodine in subgroups of men with overactive bladder symptoms and presumed non-obstructive benign prostatic hyperplasia.

OBJECTIVES: To investigate the symptomatic and quality of life (QoL) response to treatment with tolterodine extended release (ER) in subgroups of male patients with Overactive Bladder Syndrome (OAB) and LUTS suggestive of non-obstructive benign prostatic hyperplasia (BPH) according to age, symptom severity, diabetes mellitus status, and concomitant treatment for LUTS. METHODS: Patients treated with tolterodine ER 4 mg/day for OAB symptoms, alone or added to unsuccessful alpha-blocker treatment of > or =6 weeks duration, and presumed non-obstructive BPH (Q (max) > or = 15 ml/s) were observed for 12 weeks in a non-interventional study. Patients completed the International Prostate Symptom Score (IPSS) and Overactive Bladder Questionnaire (OAB-q) at baseline and after 12 weeks. RESULTS: 52.4% of 741 patients were aged < or =65 years; 4, 64, and 32% had mild, moderate, and severe symptoms, respectively, according to IPSS; 14% had diabetes mellitus, and in 42% tolterodine was added to alpha blockers. In the various subgroups, mean IPSS total scores improved by 2.8-11.1 points, IPSS QoL scores by 1.8-2.4 points, and all OAB-q subscores by more than 14 points. Only IPSS and OAB-q baseline scores had a relevant impact on changes during treatment, benefits were greatest in patients with more severe symptoms and bother. CONCLUSIONS: In men with symptoms of OAB and LUTS suggestive of non-obstructive BPH of all IPSS severity classes, aged < or =65 years or above, with or without concomitant diabetes or alpha-blockers, symptoms and QoL improved markedly during treatment with tolterodine ER.

Safety and efficacy of tolterodine extended release in men with overactive bladder symptoms and presumed non-obstructive benign prostatic hyperplasia.

Patients with presumed non-obstructive BPH (Q (max )>or= 15 ml/s) treated with tolterodine ER 4 mg/day for OAB symptoms, alone or added to unsuccessful alpha-blocker treatment of >or=6 weeks duration, were observed for 12 weeks in a non-interventional study to generate real-life efficacy and safety data. Patients completed the IPSS, the OAB-q and a 2-day micturition diary at baseline and 12 weeks. PVR was determined sonographically. Seven hundred and forty one patients were analysed. Mean PVR did not increase (25.4 +/- 26.5 vs. 29.3 +/- 30.9 ml at baseline). AUR requiring catheterization occurred in two patients, acute UTI in four patients. Median IPSS total scores decreased from 17 to 10, IPSS QoL scores from 4 to 2, OAB-q symptom bother scores from 50.0 to 22.5 and OAB-q HRQL scores increased from 59.2 to 81.6. In men with OAB symptoms and presumed non-obstructive BPH, tolterodine ER provided considerable symptomatic and QoL improvements with a low risk of AUR, acute UTI, or increased PVR.

A typology of men's sexual attitudes, erectile dysfunction treatment expectations and barriers.

In total, 1122 men completed non-validated structured interviews on sexual attitudes and on erectile dysfunction treatment expectations and barriers. Dimensions of sexual attitudes and treatment expectations and barriers were extracted by factor analysis and subjects were grouped into types by cluster analysis. Five types emerged: the sensation seeker, the sensuous, the anxious, the confident and the abstinent. The majority of men agreed on the importance of sex for the partnership. For the majority of anxious, sensuous and sensation-seeking men, sex was important for self-esteem. Expecting quality of life, enjoyment, self-esteem and hard reliable erections from treatment with phosphodiesterase-5 inhibitors, anxieties for side effects and loss of control, sexual abstinence and desire for an intensive sex life had the strongest impact on the likelihood of use. Men's sexual attitudes vary considerably and impact reactions to erection difficulties. A typology of five groups was developed, which will contribute to research on and understanding of men's sexual and treatment-seeking behaviors.

Nitrate in aquifers beneath agricultural systems.

Research from several regions of the world provides spatially anecdotal evidence to hypothesize which hydrologic and agricultural factors contribute to groundwater vulnerability to nitrate contamination. Analysis of nationally consistent measurements from the U.S. Geological Survey's NAWQA program confirms these hypotheses for a substantial range of agricultural systems. Shallow unconfined aquifers are most susceptible to nitrate contamination associated with agricultural systems. Alluvial and other unconsolidated aquifers are the most vulnerable and also shallow carbonate aquifers that provide a substantial but smaller contamination risk. Where any of these aquifers are overlain by permeable soils the risk of contamination is larger. Irrigated systems can compound this vulnerability by increasing leaching facilitated by additional recharge and additional nutrient applications. The system of corn, soybean, and hogs produced significantly larger concentrations of groundwater nitrate than all other agricultural systems because this system imports the largest amount of N-fertilizer per unit production area. Mean nitrate under dairy, poultry, horticulture, and cattle and grains systems were similar. If trends in the relation between increased fertilizer use and groundwater nitrate in the United States are repeated in other regions of the world, Asia may experience increasing problems because of recent increases in fertilizer use. Groundwater monitoring in Western and Eastern Europe as well as Russia over the next decade may provide data to determine if the trend in increased nitrate contamination can be reversed. If the concentrated livestock trend in the United States is global, it may be accompanied by increasing nitrogen contamination in groundwater. Concentrated livestock provide both point sources in the confinement area and intense non-point sources as fields close to facilities are used for manure disposal. Regions where irrigated cropland is expanding, such as in Asia, may experience the greatest impact of this practice on groundwater nitrate.

Diffuse pollution from intensive agriculture: sustainability, challenges, and opportunities.

Global expansion and intensification of industrialized agriculture during the last 50 years was facilitated by the replacement of labor by imported chemicals and energy, thus changing the economics and the social fabric of rural communities as well as impairing water, air, and soil resources essential to sustaining food and fiber production in a world with an increasing appetite. To effectively understand and solve complex problems resulting from this agricultural revolution, expanded communications are needed at a variety of levels. It is critical for the technical community to communicate through greater interdisciplinary research among agronomists, soil scientists, hydrologists, ecologists, and others to reduce diffuse pollution from agriculture. Also, more effective translations of technical problems and solutions are needed to influence policy. Accurate advice is needed in spite of the uncertainties that scientists too often use to obscure useful information. Education will be needed for producers and conservationists to gain confidence that promised environmental responses will occur if solutions are to be implemented at more than experimental or demonstration scales. The search for comprehensive solutions to environmental degradation will require understanding the ultimate causes of pollution, not just the proximal causes. The ultimate causes will only be found by examining the systems that facilitate the release of contaminants to the environment such as the wholesale landscape changes that replaced grazing land with annual crops leading to increased leaching and runoff. Research and demonstration projects increasingly need collaborations among agronomists, livestock scientists, soil scientists, hydrologists, economists, sociologists and others who have a stake in the study of diffuse pollution and the outcomes of any proposed solutions. Partnerships developed at the working level where basic principles can be shared will help avoid the pursuit of impractical solutions when viewed from different perspectives.

[Strategies for talking to the patient with sexual dysfunction in the doctor's office]. / Tabuthema Sexualstörung: Wie spreche ich den Patienten darauf an? Ein Fragebogen kann den Einstieg erleichtern.

The use of a questionnaire for initiating talks about the topic of sexual disorders and the efficacy and acceptance by the physician and patient of various communication strategies, were investigated. Each of a total of 1191 general practitioners distributed a health questionnaire which contained questions on sexuality to 150 men aged 30 and above. In a total of 10,622 first talks on sexual health, the questionnaire met with a high level of acceptance, and was the trigger for talks in 54% of the cases. More than two-thirds of the patients reacted positively to such talks, speaking freely and readily, and relieved that this aspect of their lives was being addressed. In 75% of the patients an erectile dysfunction was diagnosed, in 27% further diagnostic measures were prescribed, and in 60% treatment was initiated. In the exes of the physician, the clearly signaled readiness to talk and the discussion of treatment options were the most favorable communication strategies.

Integrating principles of nitrogen dynamics in a method to estimate leachable nitrogen under agricultural systems.

Surplus nitrogen (N) in ground and surface water is of concern in intensive agricultural regions. Surplus N leaches during lengthy periods where annual crop systems are used in temperate regions. This paper presents a model to estimate the surplus N available for leaching to ground water beneath agricultural systems and applies the model to watersheds in an intensive maize and soybean production system. The model utilizes commonly available georeferenced data on soils, crops, and livestock, making it applicable to watersheds in many regions. The model links stocks of N in soil, crops, livestock, fertilizer and the atmosphere. Nitrogen flow centers on exchange between the soil N stocks. Nitrogen mineralization rates are defined for three soil organic matter pools, crop residue, and manure based on carbon:N ratios. Nitrogen exports from the system are harvested crops, livestock and losses to the atmosphere. Application of the model in 26 Iowa watersheds finds surpluses of 18 to 43 kg-N/ha. Surpluses exceeded measured annual nitrate-N loads in regional streams by amounts equivalent to denitrification rates in groundwater. Deficits in soil N were sufficiently small to suggest that the system is in equilibrium with soils of the region.

[Quality assurance in the urologist's practice. Erectile dysfunction as an example of a multicenter approach to documenting treatment results]. / Qualitätssicherung in der urologischen Praxis. Erektile Dysfunktion als Beispiel für die einrichtungsübergreifende Dokumentation der Ergebnisqualität.

Of 517 urologist practices approached, 93% participated in a pilot study on the quality of care in the treatment of erectile dysfunction (ED). Treatment modalities and satisfaction were documented for 10,750 ED patients in 2002-at a time when vardenafil and tadalafil had not yet been officially approved. Psychological factors (55%), BPH (42%), and hypertension (33%) were given as the most prevalent ED risk factors; 82% of the patients received sildenafil, 20% apomorphine, 12% yohimbine, and 10% intracavernous alprostadil. Of the patients, 81% were satisfied or very satisfied with one of the treatment options offered and 85% and more were satisfied or very satisfied with sildenafil's onset of action, duration of action, efficacy, and tolerability. Of the physicians, 97% rated the opportunity to compare their own treatment results with other urologists' results as important or very important.

Erectile dysfunction (ED) is prevalent, bothersome and underdiagnosed in patients consulting urologists for benign prostatic syndrome (BPS).

OBJECTIVES: The aim of the present study was to determine the prevalence of erectile dysfunction (ED) in patients visiting office-based urologists in Germany because of lower urinary tract symptoms (LUTS) due to benign prostatic hyperplasia (BPH), and to evaluate the impact of ED on quality of life (QoL) in these patients. METHODS: 500 office-based urologists in Germany were invited to evaluate 20 consecutive patients for erectile dysfunction, who presented because of BPH-related LUTS. Physicians provided information on demographic factors, duration and treatment history of BPH, severity of LUTS, ED risk factors, and assessed the patient for the clinical diagnosis of ED. Patients were asked to complete the German version of the IPSS to measure LUTS severity. ED-patients quantified erectile dysfunction and impact on quality of life with validated German questionnaires (Cologne assessment of male erectile dysfunction KEED, and Qol-Med). RESULTS: Office-based urologists were aware of ED in 37.3% of 8768 patients presenting for LUTS before the study, 14.7% of patients were treated for ED. After the study-related assessment, physicians diagnosed ED in 62.1% of these patients and planned treatment in 46.9%. Severity of LUTS and ED prevalence correlated significantly after age-stratification. The incidence of ED was increased in patients with established ED risk factors. Mean QoL-Med score (best QoL: 100, worst QoL: 0) was 53.8 in patients with ED and 50.1 in ED-patients considering treatment. CONCLUSION: ED is highly prevalent in LUTS patients visiting an office-based urologist and is accompanied by a profound impact on the quality of life. Apparently, even during an urological consultation many ED-patients are hesitant to actively ask for treatment. Sexual issues should become key considerations for physicians managing patients with LUTS, especially since effective and well established oral treatment for ED is available.

Long-term effects of nitrogen fertilizer use on ground water nitrate in two small watersheds.

Changes in agricultural management can minimize NO3-N leaching, but then the time needed to improve ground water quality is uncertain. A study was conducted in two first-order watersheds (30 and 34 ha) in Iowa's Loess Hills. Both were managed in continuous corn (Zea mays L.) from 1964 through 1995 with similar N fertilizer applications (average 178 kg ha(-1) yr(-1)), except one received applications averaging 446 kg N ha(-1) yr(-1) between 1969 and 1974. This study determined if NO3-N from these large applications could persist in ground water and baseflow, and affect comparison between new crop rotations implemented in 1996. Piezometer nests were installed and deep cores collected in 1996, then ground water levels and NO3-N concentrations were monitored. Tritium and stable isotopes (2H, 18O) were determined on 33 water samples in 2001. Baseflow from the heavily N-fertilized watershed had larger average NO3-N concentrations, by 8 mg L(-1). Time-of-travel calculations and tritium data showed ground water resides in these watersheds for decades. "Bomb-peak" precipitation (1963-1980) most influenced tritium concentrations near lower slope positions, while deep ground water was dominantly pre-1953 precipitation. Near the stream, greater recharge and mixed-age ground water was suggested by stable isotope and tritium data, respectively. Using sediment-core data collected from the deep unsaturated zone between 1972 and 1996, the increasing depth of a NO3-N pulse was related to cumulative baseflow (r2 = 0.98), suggesting slow downward movement of NO3-N since the first experiment. Management changes implemented in 1996 will take years to fully influence ground water NO3-N. Determining ground water quality responses to new agricultural practices may take decades in some watersheds.