Housing breeding mice in three different IVC systems: maternal performance and pup development.

A proper cage environment is essential for the welfare of laboratory mice, especially for females during the energy demanding lactation period and for pups during early development and growth. The most common housing system for laboratory mice is individually ventilated cages (IVCs) of which there are different layouts and ventilation strategies available on the market. The present study investigates the impact of cage environment in three different IVC types, on the maternal performance of females, and pup development and growth in C57BL/6NCrl and Crl:NMRI Foxn1 nu mice. The results show differences in in-cage climate, female body weight, pup growth, feed and water consumption, and nest quality between cage types. There was a distinct effect of genotype in these differences, with the main effects found in NMRI NU mice. The results indicate that IVC systems might need to be managed differently for mice of different types and/or different physiological status. Many of the differences seen between cage systems could be drawn to the physical construction of the cage, such as location of feed hopper and location of air inlet and outlet. In conclusion, IVC in-cage climate affects the maternal performance of female mice and pup growth, but with differences between the two strains tested.

Quality of life before and one year following stem cell transplantation using an individualized and a standardized instrument.

OBJECTIVE: The aim was to prospectively measure quality of life in patients with malignant blood disorders following stem cell transplantation (SCT) using an individualized and a standardized measure. METHODS: Twenty-two consecutive patients were assessed before and one year following SCT, using a generic and disease-related version of the Schedule for the Evaluation of Individual Quality of Life-Direct Weighting (SEIQoL-DW) and the EORTC QLQ-C30. Results of the QLQ-C30 were compared with Swedish norm values. RESULTS: A majority of the patients reported concerns related to health before as well as one year after SCT, recorded by both instruments. Mean scores produced by the SEIQoL-DW, and four scales of the EORTC QLQ-C30, showed a change over time, indicating improved quality of life one year after SCT. In comparison with Swedish norm values for the EORTC QLQ-C30, SCT recipients reported a worse functioning. CONCLUSIONS: In addition to well-known disease and treatment-related problems, areas not typically included in standardized instruments were nominated in the disease-related SEIQoL-DW. Such areas included positive aspects, e.g. a changed view of life and oneself. The results support the use of the generic and disease-related SEIQoL-DW to achieve a comprehensive picture of patient's clinical situation under treatment or when recovering from illness.

Symptoms experienced by patients with peripheral vestibular disorders: evaluation of the Vertigo Symptom Scale for clinical application.

OBJECTIVES: To describe symptoms during an episode of dizziness in a sample of patients suffering from peripheral vestibular disorders and to compare them with the items in the Vertigo Symptom Scale. DESIGN: A descriptive study from a sample of patients with peripheral vestibular disorders. SETTING: Patients visiting a department of audiology at a university hospital. PARTICIPANTS: Twenty patients with peripheral vestibular disorders. The inclusion criteria were that the patient had had at least three spontaneous attacks of vertigo and/or was constantly unsteady during the last 3 months for at least 75% of the time when awake. MAIN OUTCOME MEASURES: Patients were instructed to complete a diary where they recorded symptoms that arose during an episode of dizziness. These symptoms were compared with the content of the Vertigo Symptom Scale. RESULTS: The most frequent symptoms as mentioned by the patients in their diaries were a feeling that things are spinning or moving around, nausea, feeling unsteady/about to lose one's balance, fatigue, headache, a feeling as if the ground you walk on is distant and ear-related such as tinnitus and a feeling of pressure in the ear. Pain in the heart or chest region, a heavy feeling in the arms or legs, pain in the lower part of the back and excessive sweating were not mentioned at all or by very few patients. Analysis showed that some of the symptoms included in the Vertigo Symptom Scale occurred less during an episode of dizziness than others in this sample of patients with peripheral vestibular disorders. CONCLUSION: It was found that the Vertigo Symptom Scale is an adequate base but may need to be developed for use in patients diagnosed with peripheral vestibular symptoms to be able to evaluate care and treatment.

Lung morphology after late fetal tracheal ligation in rats.

Pulmonary hypoplasia and persistent pulmonary hypertension are the main causes of mortality and morbidity in congenital diaphragmatic hernia (CDH). Prenatal tracheal occlusion accelerates lung growth, but the mechanism remains unknown. In order to be able to establish the accuracy of our experimental model for further molecular biological examinations, we evaluated the histologic structure of 1. fetal lungs subjected to tracheal occlusion compared to 2. normal fetal lungs, 3. hypoplastic lungs in CDH, and 4. normal neonatal lungs. One group of Sprague-Dawley rat fetuses were subjected to intrauterine tracheal ligation (TL) on gestational day 19 (n = 7). Control fetuses were obtained from the same litters as those subjected to TL (n = 8). Another group of pregnant Sprague-Dawley rats were given 100 mg nitrofen on gestational day 9.5 to create CDH (n = 8). All fetuses were delivered by cesarean section on day 21. Lungs from 1-day-old, healthy, non-operated, newborn Sprague-Dawley rats were also examined (n = 6). Lung weight to body weight ratio was significantly higher in the TL lungs (5.0 +/- 0.36 %), compared to control lungs (2.8 +/- 0.15 %), CDH lungs (1.9 +/- 0.12 %), and normal neonatal lungs (4.2 +/- 0.18 %). Volume density of alveolar air space and radial alveolar count (RAC) in TL lungs (52 +/- 1.4 %) (3.3 +/- 0.25) were significantly higher than in control lungs (34 +/- 3.4 %) (2.2 +/- 0.17) and in CDH lungs (16 +/- 1.7 %) (1.7 +/- 0.07). No significant differences were found between the TL and the normal neonatal group (59 +/- 1.4 %) (3.6 +/- 0.11). Fetal lungs after TL showed evidence of growth stimulation with increased volume density of alveolar air space and increased RAC, comparable to findings in normal neonatal lungs.

Validation of an extended version of the SEIQoL-DW in a cohort of Hodgkin lymphoma' survivors.

Individual measures of quality of life (QoL) have been initiated to overcome the possible limitations with standardized measures using predefined domains for evaluation. The Schedule for the Evaluation of Individual Quality of Life-Direct Weighting (SEIQoL-DW) uses personal interviews to explore the five most important areas in life, both positive and negative, crucial for QoL. The nominated areas are rated regarding satisfaction and weighted to capture the importance of each selected area. The Swedish version has been extended with a disease-specific module, which evaluates the areas in life influenced by disease. The aim of this study was to validate the disease-specific SEIQoL-DW and furthermore, to evaluate the influence of the importance ratings on the overall index score in a cohort of Hodgkin lymphoma survivors. The results support the construct validity of the disease-specific SEIQoL-DW and indicate that the instrument appears to be a sensitive measure with ability to differentiate between groups with disparate subjective health status. The SEIQoL-DW succeeds to capture both positive and negative areas in life influenced by disease. The present study gave no evidence that the weighting procedure has any impact on the total index. The results support the use of the new extended version including a disease-specific module.

Patients' experience of ambulatory self-administration of pamidronate in multiple myeloma.

The aim was to explore ambulatory self-administration of Pamidronate (Self-A-Pam) from a patient perspective in patients with multiple myeloma. Pamidronate is normally administered once a month as an intravenous infusion over 2 to 4 hours. Twenty-one patients were included, of whom 13 (6 women, 7 men) with a median age of 56 years (range 37-70) completed the educational program and subsequent ambulatory Self-A-Pam. An RN at the hospital initiated the Pamidronate therapy (90 mg). The patients then left hospital and later, on completion, they disconnected the infusion, either alone or with the assistance of a relative or significant other. Interviews were used to collect information about the experiences during the course of the Self-A-Pam. In total, 12 patients were interviewed after 3 doses of Self-A-Pam. One patient declined to participate in the interview. A qualitative analysis of the textual data was performed. Five main categories were identified: decision concerning Self-A-Pam, information and education, sources of practical help or support, effects of Self-A-Pam, and feelings and activities in relation to place (hospital, home, or public place). All 13 patients who started on Self-A-Pam went through 3 courses of Self-A-Pam during the study period. Many patients reported a gain in feelings of freedom/independence and time saving. However, some patients reported insufficient education and feelings of anxiety associated with the responsibility of handling the venous access device.

Percutaneous endoscopic gastrostomy (PEG) - a long-term follow-up study in head and neck cancer patients.

Many patients with head and neck cancer experience problems related to swallowing. A retrospective study of 156 consecutive patients who received a percutaneous endoscopic gastrostomy (PEG) at a teaching hospital is presented. The results showed that 42% had complications. Fatal complications were seen in connection with PEG tube placement, but severe and minor complications could occur much later. The method of PEG tube insertion did not affect the complication rates. The spectrum of observed complications is different to that reported earlier, suggesting that the learning curve of surgeons under training could have influenced the outcome. It may be concluded that for a very sick patient a theoretically easy surgical procedure could turn into a potentially dangerous operation. It is important to select suitable candidates for a PEG. Head and neck cancer patients with a PEG need special attention in connection with the PEG tube placement and also in a long perspective, e.g. by follow-up at a nurse-led outpatient clinic.

Determinants of health-related quality of life in long-term survivors of Hodgkin's lymphoma.

In this study health-related quality of life (HRQL) in long-term survivors of Hodgkin's lymphoma (HL) was evaluated and the findings were analyzed using a conceptual model developed by Wilson and Cleary. A better understanding of the relationships between the variables explaining HRQL may improve care and rehabilitation of HL patients. The populations were long-term survivors of HL (n = 121) and a control group (n = 236). Participants were approached with one semi-structured interview, an extended version of the Schedule for the Evaluation of Individual Quality of Life - Direct Weighting (SEIQoL-DW) and three standardized questionnaires: Hospital Anxiety and Depression (HAD) scale, Short Form 12 health survey questionnaire (SF-12) and Sense of Coherence (SOC) scale. No differences regarding the mean scores were found between the HL survivors and the controls except for the SF-12, where the patients considered themselves to be in poorer physical health than the controls (p < 0.01). Even though physical health was diminished, patients did not evaluate overall QoL worse compared to the controls. The major determinants of perception of general QoL were self-rated physical and mental health as well as SOC. The HRQL of persons who have survived a median of 14 years with HL is similar to that of controls.

Comparison of the analgesic efficacy of ketobemidone and morphine for management of postoperative pain in children: a randomized, controlled study.

BACKGROUND: Ketobemidone has been used as an analgesic for postoperative pain in children, but to our knowledge the effect and occurrence of adverse effects of ketobemidone compared to morphine is not known. The aim was to determine if the analgesic potency and the occurrence of adverse effects of ketobemidone differ from morphine when administered to children, as measured by patient-controlled analgesia consumption (PCA) for postoperative pain. METHODS: Sixty healthy children, aged 6 to 16 years, scheduled for elective surgery were randomized to receive either ketobemidone (Ke) 1 mg ml(-1) or morphine (Mo) 1 mg ml(-1) for postoperative pain through PCA. Drug consumption (microg kg(-1) h(-1)), the number of PCA doses, pain intensity, and adverse effects were recorded at regular intervals. RESULTS: Data on total drug consumption were based on 26 children in the Ke group and 28 in the Mo group. A non-statistically significant difference for total mean consumption of ketobemidone (18.6 microg kg(-1)h(-1)) and morphine (23.2 microg kg(-1)h(-1)) was obtained. The mean dose ratio (Mo/Ke) was 0.80 and the median was 0.94. Children's characteristics, loading dose, PCA doses, VAS scores, and adverse effects showed no significant differences between the groups. CONCLUSION: The analgesic potency and adverse effects of ketobemidone are similar to morphine when used for postoperative pain management in children.

Individual quality of life in long-term survivors of Hodgkin's lymphoma--a comparative study.

This study aimed to use an individual approach in evaluating QoL in long-term survivors of Hodgkin's lymphoma (HL) and their view of what impact the disease has had on life using an extended version of the The Schedule for the Evaluation of the Individual quality of life-Direct Weighting (SEIQoL-DW). Adult long-term survivors from HL (n = 121) were compared with a randomly selected sample of the general population in Stockholm (n = 236). The results showed that the most commonly nominated areas (> 50% of patients and controls) important in life were family, personal health, work and relations to other people. The HL survivors mentioned leisure and finances less frequently than the controls. However, neither the current status in the different areas nor the QoL index score differed between survivors and controls. Thoughts and worries around disease, fatigue and loss of energy and late effects on skin and mucous membrane were the most commonly reported problems following HL. Sixty-six percent of the survivors reported a change in their view of life and of themselves. Demographic and disease characteristics did not influence the ratings of the chosen areas. In conclusion, long-term survivors of HL seem to have adapted well to the situation of having had a life-threatening disease and undergoing treatment, as measured with SEIQoL-DW. The extended Swedish version with a disease-specific module could be of great value when identifying specific issues that are important for the patient at time of evaluation.

Etoposide induction of tumor immunity in Lewis lung cancer.

PURPOSE: To determine if the antineoplastic effect of etoposide includes alteration in Lewis lung cancer cells which evoke an immunologic response in C57B1/6 host mice. METHODS AND RESULTS: Of C57B1/6 mice injected with 10(6) Lewis lung cancer (3LL) cells followed by treatment with a single 50 mg/kg dose of etoposide (VP-16), 60% survived over 60 days, in contrast to untreated control mice which died within 30 days. Approximately 40% of surviving mice rejected a subsequent challenge with 3LL. Their splenocytes protected naive mice injected with 3LL. To test if VP-16 treatment produced alterations in 3LL cells, which induce host immunity, leading to tumor rejection, C57B1/6 mice were injected with 3LL cells that had survived an 80-90% lethal concentration of VP-16 in vitro. These cells killed 75% of recipient mice but 60% of the surviving mice rejected challenge with 3LL. Splenocytes harvested from tumor-rejecting mice protected naive mice injected with 3LL. CONCLUSION: These results support the hypothesis that in addition to its antineoplastic cytotoxic effect, VP-16 induces changes in 3LL cells which are recognized by the host immune system resulting in immune rejection of 3LL. often immunosuppressive and therapeutic advantage is generally based on the tumor cytotoxicity of individual drugs or combinations of drugs [13]. Our earlier work showed a link between the use of cytotoxic chemotherapy with etoposide (VP-16) and the induction of an immune response against syngeneic murine leukemia in the intact host [16]. VP-16 is an immunosuppressive topoisomerase II-inhibiting drug which induces tumor cell apoptosis and is frequently used clinically to treat a variety of tumors [1, 3, 9, 10]. We have noted that the addition of cyclosporin A to VP-16 produces CD8 T lymphocyte-mediated tumor-specific immunity in mice bearing L1210 leukemia [17]. We have extended these experiments to a spontaneously arising non-carcinogen-induced neoplasm, Lewis lung cancer (3LL), and now report that surviving mice successfully treated with VP-16, in the absence of cyclosporin A, reject challenge with 3LL. In addition, results are presented to show that VP-16 modifies 3LL cells rendering them immunogenic. These findings are submitted to support the hypothesis that VP-16-induced cytotoxic changes include cellular membrane alterations in 3LL cells which are recognized by the immune system and cause rejection of this syngeneic lung tumor.

Increased blood pressure and loss of anp-induced natriuresis in mice lacking DARPP-32 gene.

Atrial natriuretic peptide (ANP) is an important regulator of sodium metabolism and indirectly of blood pressure. Evidence has accumulated that ANP regulates sodium metabolism through a cascade of steps involving an increase in the level of cGMP, activation of cGMP-dependent protein kinase (PKG), and inhibition of renal tubular Na+, K+-ATPase activity. One of the major substrates for PKG is DARPP-32. In the present study we observed that ANP does not induce natriuresis in mice that lack DARPP-32. In contrast, there was a 4-fold increase in urinary sodium excretion following ANP administration to wild type mice. ANP as well as Zaprinast, a selective inhibitor of cGMP phosophodiesterase, inhibited renal Na+, K+-ATPase activity in wild type mice but had no such effect in mice lacking DARPP-32. Mean arterial blood pressure, measured in conscious animals, was significantly increased in DARPP-32 deficient mice as compared to wild type mice. The results confirm that DARPP-32 acts as a third messenger in the ANP signaling pathway in renal tissue and suggest an important role of DARPP-32 in the maintenance of normal blood pressure.

The final phase in acute myeloid leukaemia (AML): a study of cause of death, place of death and type of care during the last week of life.

The aim of this study was to increase the knowledge of the final phase in acute myeloid leukaemia (AML), a period which entails many complex medical and psychosocial decisions. Data on cause and place of death were gathered through a retrospective review of medical and nursing records of 106 patients with AML who had died during 1995-1997. We focused on the actual phase of the disease and to what extent the patients were prescribed palliative care. With increased knowledge of the dying process in AML there are options to discuss which approach would be the most preferred final phase for an AML patient.

Gender differences in perceived health-related quality of life among patients with HIV infection.

This article explores how a group of human immunodeficiency virus (HIV)-infected patients perceived their health-related quality of life (HRQOL) in relation to their coping capacity expressed as sense of coherence. The emphasis was on gender differences. The sample consisted of 55 women (29%) and 134 men (71%), receiving outpatient medical care in a hospital. Self-report instruments, the health index, the HIV symptom scale, the well-being scale, the sense of coherence (SOC) scale and the Interview Schedule for Social Interaction were used. Disease status (HIV CDC classification, absolute CD4+ lymphocyte count and HIV/RNA) was also measured, and demographic data were collected. The total sample scored significantly worse self-rated health and weaker SOC than healthy controls. The HIV-infected women were significantly younger than the men (p < 0.0001). The majority of the women (60%) were infected by heterosexual transmission and of the men (58%) by homosexual/bisexual contacts. In the univariate analysis the women scored significantly less positive well-being (p < 0.05), weaker SOC (p < 0.05), and less social support (p < 0.01) than the men despite less advanced disease. Multiple regression analyses revealed that SOC was the strongest predictor of subjective HRQOL in both genders. The results suggest that health professionals who individualize their care of HIV-infected patients should try to be sensitive to the different ways in which men and women express their HRQOL.

Combined antioxidant and COMT inhibitor treatment reverses renal abnormalities in diabetic rats.

The development and progression of diabetic nephropathy is dependent on glucose homeostasis and many other contributing factors. In the present study, we examined the effect of nitecapone, an inhibitor of the dopamine-metabolizing enzyme catechol-O-methyl transferase (COMT) and a potent antioxidant, on functional and cellular determinants of renal function in rats with streptozotocin-induced diabetes. Administration of nitecapone to diabetic rats normalized urinary sodium excretion in a manner consistent with the dopamine-dependent inhibition of proximal tubule Na,K-ATPase activity. Hyperfiltration, focal glomerulosclerosis, and albuminuria were also reversed by nitecapone, but in a manner that is more readily attributed to the antioxidant potential of the agent. A pattern of elevated oxidative stress, measured as CuZn superoxide dismutase gene expression and thiobarbituric acid-reactive substance content, was noted in diabetic rats, and both parameters were normalized by nitecapone treatment. In diabetic rats, activation of glomerular protein kinase C (PKC) was confirmed by isoform-specific translocation and Ser23 phosphorylation of the PKC substrate Na,K-ATPase. PKC-dependent changes in Na,K-ATPase phosphorylation were associated with decreased glomerular Na,K-ATPase activity. Nitecapone-treated diabetic rats were protected from these intracellular modifications. The combined results suggest that the COMT-inhibitory and antioxidant properties of nitecapone provide a protective therapy against the development of diabetic nephropathy.

Mechanism of FK 506/520 action on rat renal proximal tubular Na+, K+-ATPase activity.

BACKGROUND: The neurotransmitter in renal sympathetic nerves, norepinephrine (NE), regulates the activity of proximal tubule (PT) Na+,K+-ATPase in a bidirectional manner via stimulation of alpha- and beta-adrenoceptors. The stimulatory alpha-adrenergic pathway is mediated by calcineurin, the target molecule for FK 506 and related compounds. We examined whether the FK 506 analogue FK 520, by interrupting the calcineurin-mediated alpha-adrenergic signaling pathway, enhance the inhibitory beta-adrenergic effect of NE on PT Na+,K+-ATPase activity. METHODS: The effects of three days of treatment with FK 520 were examined on rat renal PT Na+,K+-ATPase activity, measured as ouabain-sensitive ATP hydrolysis in single, microdissected PT segments. Renal function studies, including glomerular filtration rate (GFR) and urinary excretion of N-acetyl-3-D-glucoseaminidase (NAG), were examined using conventional clearance techniques after three days of treatment with FK 506. RESULTS: FK 520 treatment induced a pronounced and dose-dependent decrease in PT Na+,K+-ATPase activity. This effect was completely reversed by the competitive FK 520 antagonist, L 685 818, indicating that the effect was dependent on inhibition of calcineurin. To test whether the FK 520-induced decrease in Na+, K+-ATPase activity was mediated by enhanced beta-adrenoceptor signaling, the FK 520 effect was examined in rats pretreated with a beta-adrenoceptor antagonist (propranolol) or rats subjected to renal denervation. Both of these procedures prevented the FK 520-induced decrease in Na+,K+-ATPase activity. Thus, during FK 520 treatment, renal sympathetic nerves mediate an inhibitory effect on PT Na+,K+-ATPase activity via beta-adrenoceptors. Propranolol pretreatment also prevented FK 506-induced decreases in GFR and urinary excretion of NAG, an index of PT dysfunction. CONCLUSIONS: The results support the hypothesis that the net effect of the neurotransmitter NE on Na+,K+-ATPase activity is dependent on the balance between the alpha- and beta-adrenergic signaling pathways and suggest that agents that interfere with these pathways may, by altering the activity of tubular Na+,K+-ATPase, also alter the function of the renal tubular epithelial cell.

Composite energy deposition kernels for focused point monodirectional photon beams.

A 3D volume overlap algorithm has been developed for converting energy deposition kernels between arbitrary 2D and 3D irradiation geometries. The kernels can be used as convolution kernels in inverse radiation therapy planning and as accurate descriptions of the dose distributions for clinically important beam geometries. The new method of dose calculation combining Monte Carlo and analytical methods has introduced an improved accuracy in dose calculation on the fractional per cent level. The comparisons are also made for a wide range of photon spectra and irradiation geometries from narrow point monodirectional pencil beams to finite uniform beams, 4pi steradians isotropically converging beams and divergent beams from isotropic point sources. It is seen that the photon scatter penumbra is highest at low photon energies whereas the secondary electron penumbra is widest at high photon energies, making low energy beams more interesting for small targets and high energy beams most useful for large deep-seated targets.

Aspects on the optimal photon beam energy for radiation therapy.

The selection of optimal photon beam energy is investigated both for realistic clinical bremsstrahlung beams and for monoenergetic photon beams. The photon energies covered in this investigation range from 60Co to bremsstrahlung and monoenergetic beams with maximum energies up to 50 MeV. One head and neck tumor and an advanced cervix tumor are investigated and the influence of beam direction is considered. It is shown that the use of optimized intensity modulated photon beams significantly reduces the need of beam energy selection. The most suitable single accelerator potential will generally be in the range 6-15 MV for both superficially located and deep-seated targets, provided intensity-modulated dose delivery is employed. It is also shown that a narrow penumbra region of a photon beam ideally should contain low-energy photons (< or =4 MV), whereas the gross tumor volume, particularly when deep-seated targets are concerned, should be irradiated by high-energy photons. The regions where low photon energies are most beneficial are where organs at risk are laterally close to the target volume. The situation is completely changed when uniform or wedged beams are used. The selection of optimal beam energy then becomes a very important task in line with the experience from traditional treatment techniques. However, even with a large number of uniform beam portals, the treatment outcome is substantially lower than with a few optimized intensity-modulated beams.

Prenatal dexamethasone causes oligonephronia, sodium retention, and higher blood pressure in the offspring.

Recent reports have shown that low birth weight infants have a higher incidence of adult hypertension. These observations have stimulated a number of studies designed to evaluate the mechanisms of this phenomenon. In this study, fetal growth retardation was induced by treating pregnant rats with dexamethasone. After birth, pups whose mothers were treated with dexamethasone had a lower body and kidney weight and a lower number of glomeruli than control pups. Immunohistochemistry on treated kidneys demonstrated a marked reduction in the number of cells undergoing mitosis in the cortical nephrogenic zone. In the treated group, body and kidney weight normalized by 60 d of age, but blood pressure was significantly higher compared with controls (130+/-4 versus 107+/-1 mm Hg). In addition, GFR was significantly lower, albuminuria was higher, urinary sodium excretion rate and fractional sodium excretion were lower, and sodium tissue content was higher. In contrast, when pregnant rats were treated with a natural glucocorticoid (hydrocortisone) which is metabolized by the placenta, fetal development and adult blood pressure were normal. In conclusion, we found that high levels of maternal glucocorticoids impair renal development and lead to arterial hypertension in offspring. Even though renal mass eventually normalizes, glomerular damage as well as sodium retention occur and these factors may contribute to the development of hypertension.

The renal dopamine system.

Intrarenally formed dopamine induced natriuresis by inhibiting the activity of renal tubular Na/KATPase. This effect is mediated via a complex signal network, which includes inhibition of PP1 via the adenylyl cyclase-PKA-DARPP32 pathway and activation of PKC via the PLA2-arachidonic acid-20HETE pathway. The renal dopamine availability is a major determinant of the natriuretic effect of dopamine and is to a large extent modulated by the activity of COMT. The possibility that regulation of dopamine storage and release influences renal dopamine effects should be considered.