Treatment of methicillin-sensitive Staphylococcus aureus bacteremia secondary to septic phlebitis using dalbavancin.

WHAT IS KNOWN AND OBJECTIVE: Treatment of bacteremia due to Staphylococcus aureus often requires prolonged therapy leading to increased hospital lengths of stay and associated costs. For certain patients, referral to an outpatient parenteral antimicrobial therapy (OPAT) programme serves as an alternative to increased inpatient length of stay. We report an alternative to OPAT using dalbavancin for the treatment of methicillin-sensitive Staphylococcus aureus (MSSA). CASE SUMMARY: A 54-year-old Caucasian man was brought to the emergency department from a rehabilitation centre with altered mental status and possible seizure. A peripheral intravenous catheter was placed in the left forearm, and the patient was transferred to the intensive care unit (ICU) for management of his acute psychosis, possible seizure and hyponatremia. Seven days into admission, the patient became febrile thought to be secondary to septic phlebitis of the forearm. Blood cultures were taken and organism identification using Nanosphere Verigene® BC-GP rapid diagnostic testing resulted in MSSA. The patient received treatment with cefazolin with a planned treatment duration of 14 days but because of the patient's history of alcohol abuse, psychosis requiring hospitalization via the Baker Act, and history of non-compliance to follow-up appointments, the patient was deemed ineligible for OPAT. Due to the limited treatment options, therapy for MSSA bacteremia was changed on day 6 of cefazolin therapy to dalbavancin to complete the 14-day treatment duration. Blood cultures were negative at the end of treatment and no relapse of infection occurred. WHAT IS NEW AND CONCLUSION: To our knowledge, this is the first case report using dalbavancin in clinical practice for the treatment of MSSA bacteremia secondary to septic phlebitis. This report highlights the potential role of the newer lipoglycopeptides, such as dalbavancin, in treating patients who require long-term parenteral antimicrobial therapy and are ineligible for treatment via OPAT.

Indicators for childhood asthma in Spain, using the Rand method.

OBJECTIVE: To develop quality indicators to measure asthma care in primary health care. METHOD: A modified RAND was used, which included the systematic review of the literature in Embase, Cochrane and Pubmed Quality Agencies and Database. The work group identified the indicators, translated them into Spanish and resolved any duplicates. Each indicator is composed of several dimensions (access to care, clinical effectiveness, patient-centred quality and patient safety). A multidisciplinary panel of 98 professionals from all over Spain were invited to score each indicator using a Likert scale. After calculating the average and median of each indicator, this information was sent to those who responded (n=38) for a second round and further scoring. The agreement percentage for the group was obtained for each indicator. RESULTS: Of the 105 asthma indicators reviewed, we selected 46 that were presented to the panel of experts. In both Delphi phases, 37.1% of the members of the initial panel of experts responded. Of these, 26 were primary care paediatricians, six were pulmonologists, three were nurses, two were pharmacists and one was an allergist. For 32 indicators, agreement exceeded 70% and seven of those scored highest for the various care aspects for asthmatic children. CONCLUSION: Quality indicators are presented for the follow-up of asthma and their implementation in primary care, which have undergone a strict selection and agreement process by a multidisciplinary work group.

[Functional improvement in frail older adults through the Vivifrail exercise program, during two years of pandemic]. / Mejora funcional en personas mayores frágiles mediante el programa de ejercicios Vivifrail, durante dos años de pandemia.

BACKGROUND AND OBJECTIVE: Physical exercise increases functional capacity in older adults, helping to prevent or delay dependence. This study evaluates the impact of a multicomponent physical exercise intervention based on the Vivifrail program, conducted in a primary care center over two years coinciding with the COVID pandemic. SUBJECTS AND METHODS: Descriptive longitudinal design with before-after comparison without control group. Participants were older than 65 years old with functional impairment measured by execution test, enrolled in the El Palo Health Center, Málaga. The intervention consists of two weekly group sessions of physical exercise guided by a monitor, according to the Vivifrail program. VARIABLES: Barthel Index, Gait Speed, Vivifrail Category, Quality of Life (EuroQol 5-D [EQ-5D]), use of walking aids, number of falls in the previous year. MEASUREMENTS: baseline, second (one year) and final (two years). Analysis of the Kruskal-Wallis test, significance level 0.05. RESULTS: Twenty patients were evaluated. Between the first and second evaluation, we observed a significant modification in the use of walking aids (p 0.01) and Vivifrail categories: from an initial B category, 50% remained, 25% moved to A, 16.7% to C2 and 8.3% to D (p 0.048). In the analysis of the baseline-final evaluation, we found a statistically significant improvement in quality of life measured by EQ-5D (mean increase of 24 points in today's quality of life measurement, EQ-5D thermometer, with 95% CI (9.6-38.3), p 0.004) and Vivifrail category (n=10) with 60% remaining in category B and 40% moving to D (autonomous) (p<0.0001). There was a trend towards improvement in gait speed, daily walking time, and number of falls, but without reaching statistical significance. CONCLUSIONS: Multicomponent physical exercise improves perceived quality of life measured by EQ-5D and leads to a trend towards improvement in functional capacity, mood, and number of falls.

Pattern of long-term weight and metabolic changes after a first episode of psychosis: Results from a 10-year prospective follow-up of the PAFIP program for early intervention in psychosis cohort.

BACKGROUND: People with psychosis are at higher risk of cardiovascular events, partly explained by a higher predisposition to gain weight. This has been observed in studies on individuals with a first-episode psychosis (FEP) at short and long term (mainly up to 1 year) and transversally at longer term in people with chronic schizophrenia. However, there is scarcity of data regarding longer-term (above 3-year follow-up) weight progression in FEP from longitudinal studies. The aim of this study is to evaluate the longer-term (10 years) progression of weight changes and related metabolic disturbances in people with FEP. METHODS: Two hundred and nine people with FEP and 57 healthy participants (controls) were evaluated at study entry and prospectively at 10-year follow-up. Anthropometric, clinical, and sociodemographic data were collected. RESULTS: People with FEP presented a significant and rapid increase in mean body weight during the first year of treatment, followed by less pronounced but sustained weight gain over the study period (Δ15.2 kg; SD 12.3 kg). This early increment in weight predicted longer-term changes, which were significantly greater than in healthy controls (Δ2.9 kg; SD 7.3 kg). Weight gain correlated with alterations in lipid and glycemic variables, leading to clinical repercussion such as increments in the rates of obesity and metabolic disturbances. Sex differences were observed, with women presenting higher increments in body mass index than men. CONCLUSIONS: This study confirms that the first year after initiating antipsychotic treatment is the critical one for weight gain in psychosis. Besides, it provides evidence that weight gain keep progressing even in the longer term (10 years), causing relevant metabolic disturbances.

Renal lithiasis in pediatric patients: correlation of methods that depend on 24-hour collections with simpler methods that do not require timed urine. / Litiasis en pediatría: correlación de métodos que dependen de la recogida de orina de 24 horas con otros más sencillos que no requieren orina minutada.

INTRODUCTION: Daily practice requires quick, simple and accessible methods to appropriately assess the urinary excretion of solutes in diagnostic or follow-up evaluations of children with renal lithiasis. OBJECTIVES: The objective of this study was to correlate urine elimination of substances related to renal lithiasis that depend on the volume of excreted urine in a unit of time with other parameters that are calculated by measuring the concentration of these substances in blood and urine, such as urinary ratios, fractional excretions and excretion rates. MATERIALS AND METHODS: The study included 401 healthy children aged 3-14 years (187 boys and 214 girls), mean age 8.78±3.40 years. The analysis was carried out by Pearson's correlation coefficient. RESULTS: There was significant correlation between the elimination of sodium, potassium and chlorine in 24-hour urine sample and the urinary ratios and fractional excretions of these ions. Urinary ratios and rates of excretion of calcium, uric acid, phosphate, magnesium, citrate and oxalate were highly correlated with the determinations of these substances in 24-hour collections. CONCLUSIONS: These equations provide relevant information for the study of the etiology of renal lithiasis in children, as well as about compliance to dietary treatment. They also assess the effectiveness of the various treatments used in these patients, without having to resort to 24-hour collections, which pose a considerable challenge in the pediatric age group.

Validation of the index of consciousness during sevoflurane and remifentanil anaesthesia: a comparison with the bispectral index and the cerebral state index.

BACKGROUND: The purpose of this study was to validate a new level of consciousness monitor derived from the EEG, called the index of consciousness (IoC), by comparing it with the bispectral index (BIS) and the cerebral state index (CSI) during general anaesthesia for cardiac surgery using sevoflurane, remifentanil, and atracurium. METHODS: After ethical committee approval and written patient consent, data from 35 patients [31 males, four females, age 55 (10) yr] were recorded during general anaesthesia for elective cardiac bypass surgery. All patients were induced with sevoflurane 8%, until the Observer's Assessment of Alertness and Sedation (OAAS) scale level 1 was reached, and then was set at a 1% end-tidal sevoflurane concentration. Subsequently, remifentanil and atracurium were administered, the trachea was intubated, and the procedure continued as usual. To assess accuracy, the prediction probability (Pk) was calculated both during induction and during maintenance. RESULTS: The Pk values [mean (se)] for IoC, BIS, and CSI during induction were 0.90 (0.01), 0.90 (0.01), and 0.88 (0.01), respectively, whereas the corresponding Pk values during maintenance were 0.95 (0.01), 0.94 (0.01), and 0.60 (0.01). CONCLUSIONS: The three indices performed equally well during the induction phase and were able to predict the level of consciousness of the patients satisfactorily. During maintenance, the IoC and the BIS showed good agreement with the clinical signs. The CSI was significantly influenced by the administration of atracurium; therefore, the agreement with the OAAS scale during the maintenance phase was significantly less for CSI than for IoC and BIS.

Characterization of Gene Expression in the Rat Brainstem After Neonatal Hypoxic-Ischemic Injury and Antioxidant Treatment.

The perinatal brainstem is known to be very vulnerable to hypoxic-ischemic events which can lead to deafness, swallowing dysfunction, and defective respiratory control. The aim of the present work was to evaluate the potential neuroprotective effects of nicotine, melatonin, resveratrol, and docosahexaenoic acid on the expression of a panel of genes in the brainstem following hypoxic-ischemic damage. Quantitative PCR was used to examine gene expression 3 and 12 h after the damage, and immunohistochemistry was employed to evaluate neurons, astrocytes, and synaptic vesicles 24 h post insult. We found that the expression of some immediate-early genes, as well as that of inflammatory genes TNF-α, COX2, and caspase 3, was upregulated in response to the insult. Twenty-four hours after the damage, the percentage of NeuN and synaptophysin immunolabeled cells was found to be reduced while GFAP expression was upregulated. No differences were observed in ROS gene expression following treatments.

Docosahexaenoic Acid Reduces Cerebral Damage and Ameliorates Long-Term Cognitive Impairments Caused by Neonatal Hypoxia-Ischemia in Rats.

As the interest in the neuroprotective possibilities of docosahexaenoic acid (DHA) for brain injury has grown in the recent years, we aimed to investigate the long-term effects of this fatty acid in an experimental model of perinatal hypoxia-ischemia in rats. To this end, motor activity, aspects of learning, and memory function and anxiety, as well as corticofugal connections visualized by using tracer injections, were evaluated at adulthood. We found that in the hours immediately following the insult, DHA maintained mitochondrial inner membrane integrity and transmembrane potential, as well as the integrity of synaptic processes. Seven days later, morphological damage at the level of the middle hippocampus was reduced, since neurons and myelin were preserved and the astroglial reactive response and microglial activation were seen to be diminished. At adulthood, the behavioral tests revealed that treated animals presented better long-term working memory and less anxiety than non-treated hypoxic-ischemic animals, while no difference was found in the spontaneous locomotor activity. Interestingly, hypoxic-ischemic injury caused alterations in the anterograde corticofugal neuronal connections which were not so evident in rats treated with DHA. Thus, our results indicate that DHA treatment can lead to long-lasting neuroprotective effects in this experimental model of neonatal hypoxia-ischemic brain injury, not only by mitigating axonal changes but also by enhancing cognitive performance at adulthood.

Current concepts in the diagnosis and management of metabolic complications of HIV infection and its therapy.

Changes in fat distribution, dyslipidemia, disordered glucose metabolism, and lactic acidosis have emerged as significant challenges to the treatment of human immunodeficiency virus (HIV) infection. Over the past decade, numerous investigations have been conducted to better define these conditions, identify risk factors associated with their development, and test potential therapeutic interventions. The lack of standardized diagnostic criteria, as well as disparate study populations and research methods, have led to conflicting data regarding the diagnosis and treatment of metabolic and body shape disorders associated with HIV infection. On the basis of a review of the medical literature published and/or data presented before April 2006, we have prepared a guide to assist the clinician in the detection and management of these complications.

[Management of transient radicular pain after receiving an epidural blood patch for headaches due to spontaneous intracranial hypotension]. / Radiculalgia transitoria tras administración de parche hemático epidural en la cefalea por hipotensión intracraneal espontánea, conducta a seguir.

Spontaneous intracranial hypotension headache is an uncommon disease that resolves spontaneously in most of the cases and in a short period of time. The initial treatment should be symptomatic. In some patients the symptomatology is extremely disabling, and in these cases both the diagnosis and treatment may be performed by an epidural blood patch. A 49-year-old Caucasian woman, with no previous record of epidural or intrathecal puncture, consulted in the Emergency Department complaining of a 9-day history of frontal headache and diplopia, along with nausea and vomiting. The patient was diagnosed with spontaneous intracranial hypotension headache. Considering the symptomatology and the uncontrolled pain, the Pain Unit of our hospital performed an epidural blood patch. In the first 24h the patient reported a remarkable relief of both headache and diplopia but developed a left lumbar radiculopathy that was treated successfully with supportive measures. Transient lumbar radiculopathy is a common and acceptable event secondary to the use of epidural blood patch as a treatment for spontaneous intracranial hypotension headache.

Urban NH3 levels and sources in six major Spanish cities.

A detailed spatial and temporal assessment of urban NH3 levels and potential emission sources was made with passive samplers in six major Spanish cities (Barcelona, Madrid, A Coruña, Huelva, Santa Cruz de Tenerife and Valencia). Measurements were conducted during two different periods (winter-autumn and spring-summer) in each city. Barcelona showed the clearest spatial pattern, with the highest concentrations in the old city centre, an area characterised by a high population density and a dense urban architecture. The variability in NH3 concentrations did not follow a common seasonal pattern across the different cities. The relationship of urban NH3 with SO2 and NOX allowed concluding on the causes responsible for the variations in NH3 levels between measurement periods observed in Barcelona, Huelva and Madrid. However, the factors governing the variations in A Coruña, Valencia and Santa Cruz de Tenerife are still not fully understood. This study identified a broad variability in NH3 concentrations at the city-scale, and it confirms that NH3 sources in Spanish urban environments are vehicular traffic, biological sources (e.g. garbage containers), wastewater treatment plants, solid waste treatment plants and industry. The importance of NH3 monitoring in urban environments relies on its role as a precursor of secondary inorganic species and therefore PMX. Further research should be addressed in order to establish criteria to develop and implement mitigation strategies for cities, and to include urban NH3 sources in the emission inventories.

Delayed apoptotic pyramidal cell death in CA4 and CA1 hippocampal subfields after a single intraseptal injection of kainate.

We have performed a detailed time-course analysis of cell death in the hippocampal formation, basal forebrain and amygdala following a single intraseptal injection of kainate in adult rats. Acetylcholinesterase histochemistry revealed a profound loss of staining in the medial septum but not in the diagonal band, and cholinergic fiber density was highly reduced in the hippocampus and amygdala at 10 days postinjection. Terminal deoxynucleotidyl transferase-mediated uridine 5'-triphosphatebiotin nick end labeling (TUNEL) histochemistry was performed for precise location of apoptotic cells. Both the medial septum and amygdala exhibited numerous TUNEL-positive nuclei after the intraseptal injection of kainate, while the lateral septum exhibited a lower but significant incidence in terms of apoptotic cells. In the medial septum, the presence of apoptotic cells was at a location displaying acetylcholinesterase staining. TUNEL histochemistry revealed a time-dependent sequential apoptotic cell death in hippocampal pyramidal cells. During the first two days postinjection, apoptosis in the hippocampus was only evident in the CA3 region. At five days postinjection, the entire CA4 region became apoptotic. At 10 days postinjection, the whole extent of the CA1 pyramidal cell layer exhibited numerous TUNEL-positive nuclei. The time-course of kainate-induced apoptosis in Ammons's horn correlated with the disappearance of hippocampal pyramidal neurons as detected by Nissl staining, which is suggestive of a prominent apoptotic death for these cells. The temporal delayed distant damage to CA4 and CA1 hippocampal subfields after a single intraseptal kainate injection is not seen in other models employing kainate and may be a valuable tool for exploring the cellular mechanisms leading to cell death in conditions of status epilepticus.

Serotonin hyperinnervation in the adult rat ventral mesencephalon following unilateral transection of the medial forebrain bundle. Correlation with reactive microglial and astroglial populations.

We have previously studied changes in the serotoninergic and dopaminergic nigrostriatal systems following transection of the medial forebrain bundle and found a long-term axotomy-induced increase in the levels of serotonin and its main metabolite, 5-hydroxyindolacetic acid in substantia nigra [Venero et al. (1997) J. Neurochem. 68, 2458-2468]. In an attempt to find a rationale for this effect, we have performed an immunohistochemical study. Transection of the medial forebrain bundle of the rat interrupted most of the ascending serotoninergic pathways from the raphe nuclei as revealed by serotonin immunoreactivity. While serotonin immunostaining was almost absent in striatum, it doubled in the ventral mesencephalon at 21 days postlesion. This axotomy-induced increase was accompanied by an increased density of the serotonin nerve terminal network in the ipsilateral substantia nigra and ventral tegmental area. The increase in serotonin immunoreactivity was in line with the measured levels of serotonin and 5-hydroxyindolacetic acid in substantia nigra. In addition, the distribution pattern of glial fibrillary acidic protein-immunoreactive astrocytes and OX42-immunoreactive microglia correlated highly with the location of increased serotonin fibre density in the ventral mesencephalon, especially in ventral tegmental area and in the most medial part of substantia nigra. We suggest that a pruning effect may underly the axotomy-induced increase in serotonin immunoreactivity in the ventral mesencephalon, and further, that activated astroglia and microglia may play a role in directing serotoninergic axonal regeneration following axotomy.

Long-lasting induction of brain-derived neurotrophic factor is restricted to resistant cell populations in an animal model of status epilepticus.

We have recently characterized an animal model of status epilepticus induced by a single intraseptal injection of kainate. Under these conditions, there is a delayed expanding apoptotic hippocampal and amygdalar cell death. In order to further characterize this animal model, we have performed a detailed time-course analysis of the appearance of cell death, brain-derived neurotrophic factor messenger RNA expression and astroglial and microglial response in different brain areas related to the limbic system. We found a long-lasting delayed apoptotic cell death in the hippocampal formation, amygdala, medial thalamus, dorsal endopiriform nucleus and multiple cortical areas from two to 21 days post-injection. There was a spatiotemporal correlation between the appearance of cell death and induction of brain-derived neurotrophic factor messenger RNA expression in the areas studied, and interestingly this induction was found in non-degenerating cells. We conclude that our animal model of status epilepticus exhibits remarkable features of recurrent seizure activity and provides evidence for a neuroprotective role of brain-derived neurotrophic factor against seizure-induced apoptotic cell death.

Less induced 1-methyl-4-phenylpyridinium ion neurotoxicity on striatal slices from guinea-pigs fed with a vitamin C-deficient diet.

The effect of ascorbic acid depletion on the 1-methyl-4-phenylpyridinium ion (MPP+)-induced neurotoxicity in the dopaminergic system has been tested in guinea-pig striatal slices. Guinea-pigs were divided into three groups and fed on a control diet, ascorbic acid-free diet and ascorbic acid-supplemented diet, respectively. Diets were maintained during 30 days. Striatal slices from ascorbic acid-deficient animals showed the highest levels of dopamine following 25 microM MPP+ treatment; the results from animals under this treatment condition were statistically different from both control and ascorbic acid-supplemented animals under identical experimental conditions. In addition, neurochemical analysis demonstrated that the levels of ascorbic acid and dehydroascorbic acid were highly reduced in striatal tissue from ascorbic acid-deficient animals, thus proving scorbutic conditions in our experimental animals. In view of the higher resistance of the ascorbic acid-deficient animals to the neurotoxicity elicited by MPP+, additional dopaminergic parameters were also measured in striatal tissue from ascorbic acid-deficient animals in the absence of MPP+, including levels of dopamine and its metabolites, tyrosine hydroxylase activity and dopamine uptake, with the aim of finding an explanation for this unexpected result. While dopamine levels and tyrosine hydroxylase activity remained close to control levels, dopamine uptake was significantly reduced in striatal synaptosomes from ascorbic acid-deficient animals as compared with control animals. Since MPP+ is actively accumulated into dopaminergic nerve terminals via the high-affinity dopamine uptake system, this finding could explain the higher resistance of ascorbic acid-deficient animals to the dopamine-depleting effect induced by MPP+ toxicity assayed in striatal slices.

Intrastriatal quinolinic acid injections protect against 6-hydroxydopamine-induced lesions of the dopaminergic nigrostriatal system.

We tested the effect of intrastriatal quinolinic acid (QA) injections 2 weeks before subsequent intrastriatal injections of 6-hydroxydopamine (6-OHDA). Levels of DA and its metabolites were measured 2 days and 21 days after lesioning the dopaminergic nigrostriatal system with 6-OHDA. Intrastriatal 6-OHDA injections in the absence of prior treatment of QA significantly decreased dopamine (DA) and its metabolite levels in striatum but not in substantia nigra at day 2, and in striatum and substantia nigra at day 21, a clear indication of a time-dependent retrograde axonal degeneration of substantia nigra cell bodies. Intrastriatal QA injections 2 weeks before subsequent intrastriatal injection of 6-OHDA partially prevented the 6-OHDA-depleting effect on DA and its metabolite levels in both striatum and substantia nigra 21 days after 6-OHDA injection. However, no statistically significant differences were found between QA + 6-OHDA- and 6-OHDA-treated animals at day 2. Our results suggest that intrastriatal QA injections partially prevent the naturally-occurring retrograde axonal degeneration of substantia nigra cell bodies caused by 6-OHDA, and illustrate a target-derived interaction between dopaminergic nerve endings and cell bodies. We suggest that the protective effect found in the QA-injected animals against the neurotoxic action of 6-OHDA is mediated by neurotrophic agents released by activated astroglia.

Mechanisms involved in kaempferol-induced relaxation in rat uterine smooth muscle.

The effect of kaempferol on KCI (60 mM)-induced tonic contraction in isolated rat uterus and its modification by inhibitors of cAMP-dependent protein kinase (PKA) (Rp-cAMPS and TPCK), phosphodiesterase (papaverine), adenylyl cyclase (2',3'-dideoxyadenosine, DDA), transcription (actinomycin D), protein synthesis (cycloheximide) and ornithine decarboxylase (alpha-difluoromethyl-ornithine, DFMO), as well as a polyamine, spermine, have been assayed. Kaempferol (3 to 60 microM) induced concentration-dependent relaxation on KCl-induced tonic contraction (IC50: 10.1 +/- 1.89 microM). This relaxing effect was antagonized (p<0.05) by Rp-cAMPS (10 microM), TPCK (3 microM), DDA (100 microM), actinomycin D (4 and 12 microM), cycloheximide (100 microM), DFMO (10 mM), actinomycin D (12 microM) plus TPCK and actinomycin D (12 microM) plus spermine (1 mM). Furthermore, the displacement obtained with actinomycin D plus DFMO was not statistically significant. Our results suggest that kaempferol through cAMP produces transcriptional events and polyamines are, at least partially, involved in the relaxant effect of kaempferol.

Pharmacological evidence for the contribution of polyamines as mediators of the transcriptional component involved in smooth muscle relaxation elicited by forskolin.

To study whether cAMP-dependent transcriptional effect and polyamines might play a modulatory role on smooth muscle, the effect of forskolin on KCl (60 mM)-induced contractions in isolated rat uterus and its modification by inhibitors of cAMP-dependent protein kinase (PKA) (Rp-cAMPS and TPCK), transcription (actinomycin D), protein synthesis (cycloheximide) and ornithine decarboxylase (alpha-difluoromethyl-ornithine, DFMO), and a polyamine (spermine) have been assayed. Forskolin (0.1 to 6 microM) induced concentration-dependent relaxation on KCl-induced tonic contractions in rat uterus (IC50: 0.55 +/- 0.12 microM) which was antagonized (p<0.05) by Rp-cAMPS (30 microM), TPCK (3 microM), cycloheximide (300 microM), actinomycin D (4 and 12 microM) and TPCK (3 microM) plus actinomycin D (12 microM). The IC50 values of forskolin in the presence of these drugs were 3.75 +/- 1.53 microM, 12.08 +/- 8.18 microM, 6.88 +/- 5.02 microM, 3.80 +/- 2.35 and 5.31 +/- 2.80 microM, and 4.26 +/- 3.65 microM respectively. Furthermore, DFMO (10 mM) also shifted the relaxation curve to forskolin to the right (IC50: 3.06 +/- 2.66 microM, p<0.05) but DFMO (10 mM) plus actinomycin D (12 microM) (IC50: 1.78 +/- 1.33 microM) did not. However, DFMO (10 mM) and actinomycin D (12 microM) did not antagonize the spermine (1-30 mM)-elicited relaxation (IC50s: 7.8 +/- 0.7 mM vs 7.28 +/- 1.4 mM and 4.67 +/- 0.44 mM in the presence of DFMO and actinomycin D, respectively). Moreover, spermine (1 mM) did not decrease the forskolin induced relaxation and counteracted the antagonism produced by actinomycin D and DFMO. Our results suggest that, in rat uterus, forskolin: a) produced cAMP-dependent relaxation, as this is antagonized by Rp-cAMP and TPCK, and b) increased the activity of ornithine decarboxylase, as this is inhibited by DFMO. Therefore, polyamines could be the mediator of the cAMP-dependent transcriptional component involved in forskolin relaxation, since, as mentioned, DFMO antagonized this relaxation and spermine counteracted the displacement produced by DFMO and actinomycin D. Thus, a plasma membrane-nucleus interaction might, at least partially, explain the mechanisms involved in forskolin induced relaxation in smooth muscle of rat uterus under the present experimental conditions.