Diagnostic accuracy and predictive validity of combined use of Fototest and Mini-Cog in cognitive impairment.

INTRODUCTION: The Fototest and Mini-Cog include all the domains that are necessary in a cognitive assessment. This study aims to evaluate the diagnostic accuracy of the combined use of both instruments for detecting cognitive impairment. METHODS: We performed a phase III diagnostic accuracy study with 2 independent samples: STUDY, which included 448 participants randomly allocated to 2 datasets (BASE [80%] and TEST [20%]); and EXTERNAL, which included 61 participants. The index test was consecutive administration of the Fototest and Mini-Cog, and the reference test was formal cognitive assessment. We evaluated the diagnostic accuracy of two-step vs consecutive application of the tests and simple (Comb-Simple), logistic regression (Comb-LR), and random decision tree (Comb-RDT) models of their combined use for detecting cognitive impairment (Global Deterioration Scale score ≥ 3). We performed an exploratory analysis of the BASE dataset, selecting criteria that maximise accuracy; a pre-specified analysis was used to evaluate the selected criteria in the TEST and EXTERNAL datasets. RESULTS: The diagnostic accuracy (95% confidence interval) of the combined models in the BASE dataset (Comb-Simple: 88.3 [88.5-91.4]; Comb-LR: 91.6 [88.2-94.3]; Comb-RDT 95.2 [92.5-97.2]) was significantly higher than the individual values observed for the Mini-Cog and Fototest (81.6 [77.1-85.4] and 84.9 [80.8-88.5], respectively). These results were replicated in the TEST (Comb-Simple: 88.9; Comb-LR: 95.6; Comb-RDT: 92.2) and EXTERNAL datasets (Comb-Simple: 91.8; Comb-LR: 90.2; Comb-RDT: 88.5). Two-step application had the same diagnostic accuracy than consecutive application but required less time (mean [SD] of 197.3 s [56.7] vs 233.9 s [45.2]; P < .0001). CONCLUSIONS: Combined application of the Fototest and Mini-Cog takes less than 4 minutes and improves the diagnostic accuracy of both instruments. Two-step application is more efficient as it requires less time while maintaining the same diagnostic accuracy.

Assessment of the diagnostic accuracy and discriminative validity of the Clock Drawing and Mini-Cog tests in detecting cognitive impairment.

INTRODUCTION AND OBJECTIVES: The Mini-Cog is a very brief, widely used cognitive test that includes a memory task and a simplified assessment of the Clock Drawing Test (CDT). There is not a formal evaluation of the Mini-Cog test in Spanish. This study aims to analyse the diagnostic usefulness of the Mini-Cog and CDT for detecting cognitive impairment (CI). METHODS: We performed a cross-sectional study, systematically including all patients who consulted at our neurology clinic over a 6-month period. We assessed diagnostic usefulness for detecting CI (defined according to the National Institute on Aging-Alzheimer's Association criteria for mild cognitive impairment and dementia) according to the area under the receiver operating characteristic curve (AUC). Sensitivity, specificity, and positive and negative likelihood ratios were calculated for each cut-off point. RESULTS: The study included 581 individuals (315 with CI); 55.1% were women and 27.7% had not completed primary studies. The Mini-Cog showed greater diagnostic usefulness than the CDT (AUC ±â€¯sensitivity: 0.88 ±â€¯0.01 vs 0.84 ±â€¯0.01; P < .01). Both instruments were less useful for screening in individuals with a low education level (0.74 ±â€¯0.05 vs 0.75 ±â€¯0.05, respectively). A cut-off point of 2/3 in the Mini-Cog achieved a sensitivity of 0.90 (95% CI, 0.87-0.93) and a specificity of 0.71 (95% CI, 0.65-0.76); a cut-off point of 5/6 in the CDT achieved a sensitivity of 0.77 (95% CI, 0.72-0.81) and a specificity of 0.80 (95% CI, 0.75-0.85). CONCLUSION: In our neurology clinic, the Mini-Cog showed acceptable diagnostic usefulness for detecting CI, greater than that of the CDT; neither test is an appropriate instrument for individuals with a low level of education.

Diagnostic accuracy and predictive validity of associated use of Fototest and Mini-Cog in cognitive impairment. / Utilidad diagnóstica y validez predictiva del uso conjunto de Fototest y Mini-Cog en deterioro cognitivo.

INTRODUCTION: The Fototest and Mini-Cog include all the domains that are necessary in a cognitive assessment. This study aims to evaluate the diagnostic accuracy of the combined use of both instruments for detecting cognitive impairment. METHODS: We performed a phase iii diagnostic accuracy study with 2 independent samples: STUDY, which included 448 participants randomly allocated to 2 datasets (BASE [80%] and TEST [20%]); and EXTERNAL, which included 61 participants. The index test was consecutive administration of the Fototest and Mini-Cog, and the reference test was formal cognitive assessment. We evaluated the diagnostic accuracy of two-step vs. consecutive application of the tests and simple (Comb-Simple), logistic regression (Comb-LR), and random decision tree (Comb-RDT) models of their combined use for detecting cognitive impairment (Global Deterioration Scale score ≥ 3). We performed an exploratory analysis of the BASE dataset, selecting criteria that maximise accuracy; a pre-specified analysis was used to evaluate the selected criteria in the TEST and EXTERNAL datasets. RESULTS: The diagnostic accuracy (95% confidence interval) of the combined models in the BASE dataset (Comb-Simple: 88.3 [88.5-91.4]; Comb-LR: 91.6 [88.2-94.3]; Comb-RDT 95.2 [92.5-97.2]) was significantly higher than the individual values observed for the Mini-Cog and Fototest (81.6 [77.1-85.4] and 84.9 [80.8-88.5], respectively). These results were replicated in the TEST (Comb-Simple: 88.9; Comb-LR: 95.6; Comb-RDT: 92.2) and EXTERNAL datasets (Comb-Simple: 91.8; Comb-LR: 90.2; Comb-RDT: 88.5). Two-step application had the same diagnostic accuracy than consecutive application but required less time (mean [SD] of 197.3 s [56.7] vs. 233.9 s [45.2]; P<.0001). CONCLUSIONS: Combined application of the Fototest and Mini-Cog takes less than 4minutes and improves the diagnostic accuracy of both instruments. Two-step application is more efficient as it requires less time while maintaining the same diagnostic accuracy.

Assessment of the diagnostic accuracy and discriminative validity of the Clock Drawing and Mini-Cog tests in detecting cognitive impairment. / Evaluación de la utilidad diagnóstica y validez discriminativa del Test del Reloj y del Mini-Cog en la detección del deterioro cognitivo.

INTRODUCTION AND OBJECTIVES: The Mini-Cog is a very brief, widely used cognitive test that includes a memory task and a simplified assessment of the Clock Drawing Test (CDT). There is not a formal evaluation of the Mini-Cog test in Spanish. This study aims to analyse the diagnostic usefulness of the Mini-Cog and CDT for detecting cognitive impairment (CI). METHODS: We performed a cross-sectional study, systematically including all patients who consulted at our neurology clinic over a 6-month period. We assessed diagnostic usefulness for detecting CI (defined according to the National Institute on Aging-Alzheimer's Association criteria for mild cognitive impairment and dementia) according to the area under the receiver operating characteristic curve (AUC). Sensitivity, specificity, and positive and negative likelihood ratios were calculated for each cut-off point. RESULTS: The study included 581 individuals (315 with CI); 55.1% were women and 27.7% had not completed primary studies. The Mini-Cog showed greater diagnostic usefulness than the CDT (AUC±sensitivity: 0.88±0.01 vs 0.84±0.01; P<.01). Both instruments were less useful for screening in individuals with a low education level (0.74±0.05 vs 0.75±0.05, respectively). A cut-off point of 2/3 in the Mini-Cog achieved a sensitivity of 0.90 (95%CI, 0.87-0.93) and a specificity of 0.71 (95%CI, 0.65-0.76); a cut-off point of 5/6 in the CDT achieved a sensitivity of 0.77 (95%CI, 0.72-0.81) and a specificity of 0.80 (95%CI, 0.75-0.85). CONCLUSION: In our neurology clinic, the Mini-Cog showed acceptable diagnostic usefulness for detecting CI, greater than that of the CDT; neither test is an appropriate instrument for individuals with a low level of education.

Granuloma de Majocchi: una forma de infección dermatofítica invasiva / Majocchi granuloma: a form of invasive dermatophyte infection

Resumen El granuloma de Majocchi es una forma de infección atípica por dermatofitos con invasión de la dermis y el tejido celular subcutáneo, favorecida por el trauma de los folículos pilosos o la inmunosupresión del huésped. Siendo una infección poco común, se destaca en este artículo el caso de una paciente que luego de usar esteroides tópicos presentó pápulas y pústulas en vulva, sitio inusual de granuloma de Majocchi, siendo este el cuarto reporte a nivel mundial.

Abstract Majocchi granuloma is a form of atypical infection by dermatophytes with invasion of the dermis and subcutaneous tissue, favored by the trauma of hair follicles or host immunosuppression. Being a rare infection, in this article highlights the case of a patient with papules and pustules on the vulva after using topical steroids, unusual site Majocchi granuloma, which is the fourth global report.

Two dose-ranging studies with PF-04937319, a systemic partial activator of glucokinase, as add-on therapy to metformin in adults with type 2 diabetes.

AIM: To assess the efficacy and safety of a range of doses of a systemic, partial, glucokinase activator, PF-04937319, as add-on therapy to metformin, in patients with type 2 diabetes mellitus (T2DM). METHODS: Patients were randomized to once-daily PF-04937319 doses of 10, 50, 100 mg, or matching placebo (Study B1621002); or PF-04937319 doses of 3, 20, 50, 100 mg, or matching placebo (Study B1621007). Titrated glimepiride (Study B1621002) or sitagliptin (Study B1621007) were included in a double-dummy manner. The primary measure was change from baseline in glycated haemoglobin (HbA1c) at week 12. Key secondary measures included other glycaemic variables and safety and tolerability. RESULTS: In the 639 patients randomized, the minimally efficacious PF-04937319 dose was identified as 50 mg once daily. At the highest PF-04937319 dose tested (100 mg), on average, a clinically significant reduction in HbA1c [-4.94 or -5.11 mmol/mol (-0.45 or -0.47%), placebo-adjusted], which was similar to that achieved with sitagliptin [-4.69 mmol/mol (-0.43%)] but lower than that achieved with titrated glimepiride [-9.07 mmol/mol (-0.83%)], was observed. At this dose, the effect on fasting plasma glucose was not consistent between the two studies (Study B1621002 vs Study B1621007: placebo-adjusted mean change of -0.83 vs +0.50 mmol/l). PF-04937319 was well tolerated at doses up to 100 mg. Hypoglycaemia was reported in 2.5% of patients (on placebo), 5.1% of patients (on PF-04937319 100 mg), 1.8% of patients (on sitagliptin) and 34.4% of patients (on titrated glimepiride). CONCLUSIONS: In patients on metformin monotherapy, the addition of a 100-mg dose of PF-04937319 improved glycaemic control and was well tolerated.

A gene variant near ATM is significantly associated with metformin treatment response in type 2 diabetes: a replication and meta-analysis of five cohorts.

AIMS/HYPOTHESIS: In this study we aimed to replicate the previously reported association between the glycaemic response to metformin and the SNP rs11212617 at a locus that includes the ataxia telangiectasia mutated (ATM) gene in multiple additional populations. METHODS: Incident users of metformin selected from the Diabetes Care System West-Friesland (DCS, n = 929) and the Rotterdam Study (n = 182) from the Netherlands, and the CARDS Trial (n = 254) from the UK were genotyped for rs11212617 and tested for an association with both HbA(1c) reduction and treatment success, defined as the ability to reach the treatment target of an HbA(1c) ≤ 7 % (53 mmol/mol). Finally, a meta-analysis including data from literature was performed. RESULTS: In the DCS cohort, we observed an association between rs11212617 genotype and treatment success on metformin (OR 1.27, 95% CI 1.03, 1.58, p = 0.028); in the smaller Rotterdam Study cohort, a numerically similar but non-significant trend was observed (OR 1.45, 95% CI 0.87, 2.39, p = 0.15); while in the CARDS cohort there was no significant association. In meta-analyses of these three cohorts separately or combined with the previously published cohorts, rs11212617 genotype is associated with metformin treatment success (OR 1.24, 95% CI 1.04, 1.49, p = 0.016 and OR 1.25, 95% CI 1.33, 1.38, p = 7.8 × 10(-6), respectively). CONCLUSIONS/INTERPRETATION: A gene variant near ATM is significantly associated with metformin treatment response in type 2 diabetic patients from the Netherlands and the UK. This is the first robustly replicated common susceptibility locus found to be associated with metformin treatment response.

Effects of a long-acting GLP-1 mimetic (PF-04603629) on pulse rate and diastolic blood pressure in patients with type 2 diabetes mellitus.

PF-04603629, an exendin-transferrin fusion protein, is a long-acting glucagon-like peptide-1 (GLP-1) mimetic. This randomized, double-blind study characterized the safety and pharmacodynamics of a single dose of PF-04603629 (n = 57; 1-70 mg) or placebo (n = 14) in subjects with type 2 diabetes mellitus (T2DM). There were dose-dependent decreases from baseline in day 6 glucose area under the curve following a mixed meal test (-27 ± 12% with 70 mg). Most treatment-related adverse events were gastrointestinal, with nausea and vomiting most frequent at 70 mg. Pulse rate (PR) and diastolic blood pressure (DBP) increased dose dependently within the normal range. At 24 h postdose mean PR increased 23 ± 9 bpm and mean DBP increased 10 ± 5 mmHg with 70 mg. In conclusion, PF-04603629 exhibited efficacy and tolerability consistent with its mechanism of action; however, PR and DBP increased. Similar effects have been reported occasionally with other GLP-1 mimetics. These data underscore the importance of careful assessments of haemodynamic effects in GLP-1 analogues.

A Dose-Ranging Study of the DPP-IV Inhibitor PF-734200 Added to Metformin in Subjects With Type 2 Diabetes*.

The purpose of this phase 2, multicentre, randomized, double-blind, placebo-controlled, 12-week dose-ranging study was to assess the efficacy, safety, and tolerability of the dipeptidyl peptidase-IV (DPP-IV) inhibitor PF-734200 in adult subjects with type 2 diabetes who were on a stable dose of metformin. Men and women with inadequate glycaemic control with metformin as their sole diabetes medication were randomized to placebo or PF-734200 2 mg, 5 mg, 10 mg, or 20 mg every day. A population subset underwent mixed meal tolerance tests (MMTT) at baseline and week 12. A total of 301 subjects were treated. At week 12, PF-734200 doses of ≥5 mg produced a statistically significant reduction in haemoglobin A (1C) (HbA (1c)) compared with placebo. The mean (95% confidence interval) placebo-adjusted changes in HbA (1c) were -0.31% (-0.70 to 0.08), -0.74% (-1.12 to -0.36), -0.70% (-1.02 to -0.38), and -0.75% (-1.07 to -0.43) for the 2 mg, 5 mg, 10 mg, and 20 mg doses, respectively. PF-734200 20 mg significantly reduced glucose area under the curve following MMTT (-12.8% [-22.9 to -2.7]; p=0.003) compared with placebo. The reductions observed with other doses were not statistically significant. PF-734200 was safe and well tolerated at all doses tested when added to metformin. PF-734200 safely and effectively lowered HbA (1c) in subjects receiving metformin. The 20 mg dose provided the greatest improvements in post-prandial glucose.

Pancreatic perfusion of healthy individuals and type 1 diabetic patients as assessed by magnetic resonance perfusion imaging.

AIMS/HYPOTHESIS: Loss of pancreatic beta cell mass and function leads to the development of diabetes mellitus. Currently there is no technical way to non-invasively image islet function and mass. Murine models suggest that islets are highly vascularised organs that make a significant contribution to the total pancreatic blood flow. The current study was undertaken to test with arterial spin labelling (ASL) magnetic resonance imaging if islet mass and/or stimulation of human pancreatic islets by hyperglycaemia can differentially increase whole-pancreas perfusion, thereby distinguishing non-diabetic from type 1 diabetic patients. METHODS: We assessed pancreatic blood flow using ASL at baseline, during a hyperglycaemia clamp study (glucose at 11 mmol/l) and during recovery to euglycaemia. RESULTS: Seventeen healthy volunteers and seven type 1 diabetic patients were studied. In healthy volunteers we observed no change in pancreatic blood flow during the three phases of the study. A trend for an increase in blood flow was observed in the two control tissues, the liver and kidney. Similarly, there was no significant difference in blood flow during the three stages (baseline, hyperglycaemia and recovery) in diabetic patients and there was no significant difference observed between diabetic patients and normal volunteers. CONCLUSIONS/INTERPRETATION: Our data suggest that in humans neither increased demand nor islet mass has a substantial influence on pancreatic perfusion. It is possible, however, that the current state-of-the art imaging technology employed in this study might not be sensitive enough to distinguish between a true effect and noise. TRIAL REGISTRATION: ClinicalTrials.gov NCT00280085.

Características clínicas y epidemiológicas de pacientes con osteomielitis en el Instituto de Salud del Niño / Clinical and epidemiological characteristics of patients with osteomyelitis at the Institute of Child Health

Se realizó un estudio clínico epidemiológico Retrospectivo - Descriptivo en donde se analizó información obtenida en base a 100 historias clínicas en el Instituto nacional de Salud del Niño desde julio del 2004 hasta julio del 2009. El objetivo de este estudio fue Conocer las características clínicas y epidemiológicas de osteomielitis en el instituto nacional de salud del niño (INSN). De un total de 100 historias clínicas que fueron revisadas se concluyo que la presencia de de los signos y síntomas clásicos de osteomielitis (fiebre, dolor, tumefacción y enrojecimiento zona afectada) (68.2 por ciento), siendo el más común de ellos el dolor (58 por ciento); Respecto a las características epidemiológicas hubo traumatismo (76 por ciento). El hueso más afectado fue el fémur (68 por ciento), el grupo etáreo más afectado fue el escolar (45 por ciento) el género masculino fue el más afectado (63 por ciento), el antibiótico más usado fue la oxacilina (65 por ciento) Y el tratamiento más indicado fue le quirúrgico (67 por ciento)

Polycyclic aromatic hydrocarbons sorption on soils: some anomalous isotherms.

The sorption of four polycyclic aromatic hydrocarbons (PAHs), namely acenaphthene (Ac), phenanthrene (Ph), anthracene (An), and fluoranthene (Fl), on soil has been investigated. The kinetics of the sorption is characterised by the presence of two distinct periods. A fast initial stage followed by a second slower sorption process. Various kinetic models (i.e., Elvoich, Lagergren, second order and double exponential models) have been used to fit experimental data. The sorption equilibrium of individual PAHs has been assessed in the 298-333 K temperature range. Unlike Ac, Ph at 333 K and An and Fl at any temperature showed anomalous isotherms. The reason seems to rely on the "trapping" of dissolved PAHs by soil organic matter (SOM) released to water. This abnormal trend was not experienced when the isotherms were obtained for four PAHs mixture. Apparently, the most soluble Ac was capable of binding all the released material so no effect was thereafter observed.

Paraoxonase 2 (PON2) polymorphisms and development of renal dysfunction in type 2 diabetes: UKPDS 76.

AIMS/HYPOTHESIS: Identification of variants predicting development of renal dysfunction would offer substantial clinical benefits. There is evidence that coding non-synonymous variants in the gene encoding paraoxonase 2 (PON2) are associated with nephropathy in both type 1 and type 2 diabetes. METHODS: We examined the relationship between variation at the C311S and A148G polymorphisms (together with PON2 intronic variant rs12704795) and indices of renal dysfunction (progression to micro- and macroalbuminuria, plasma creatinine increases) in 3,374 newly diagnosed type 2 diabetic subjects from the UK Prospective Diabetes Study followed prospectively (median 14.0 years), using proportional hazards models, adjusted for sex, ethnicity and other known or putative risk factors. RESULTS: rs12704795 genotypes were associated with differing rates of development of microalbuminuria (relative risk [RR] for CC vs AA homozygotes 0.68 [95% CI 0.54-0.87], p=0.002) but not other measures of worsening renal function. Heterozygotes for C311S were more likely to develop microalbuminuria (RR=1.31 [95% CI 1.11-1.54], p=0.001) but less likely to double creatinine levels during follow-up (RR=0.49 [95% CI 0.27-0.89], p=0.02). There was no corroboration of this latter association for related outcomes and no prior evidence supports heterosis effects at this locus. CONCLUSIONS/INTERPRETATION: We conclude that the PON2 variants typed in this study have, at best, a small effect on the risk of renal dysfunction in type 2 diabetes.

Ecstasy-induced psychotic disorder: six-month follow-up study.

OBJECTIVE: To describe the psychiatric symptoms manifested by persons diagnosed for the first time as having ecstasy-induced psychotic disorder and to explore the evolution of their symptoms over a 6-month period. DESIGN: Observational study with a 6-month follow-up. METHOD: The subjects studied were 32 ecstasy consumers who were treated at two drug-dependency outpatient centers for hallucinatory-delusive manifestations and who were diagnosed as having ecstasy-induced psychotic disorder according to DSM-IV criteria. For the assessment of the intensity of the syndrome and its follow-up, the Brief Psychiatric Rating Scale (BPRS), the Hamilton Depression Rating Scale (HDRS) and the Clinical Global Impression (CGI) were used at the outset and after 1, 3 and 6 months. All subjects received treatment with olanzapine. RESULTS: The treatment program was completed by 96.9% of the patients. At the baseline assessment, a high incidence of symptoms of a severe psychiatric disorder was observed. From the first month the psychotic symptoms (BPRS) were considerably reduced with treatment, with the most severe positive symptoms remitting in the first 3 months. The three assessment indicators (BPRS, HDRS and CGI) showed a statistically significant clinical reduction over the 6 months of the assessment period. Furthermore, no relevant side effects were noted. CONCLUSIONS: In its initial manifestations, a drug-induced psychotic syndrome includes marked symptoms meeting the criteria of a severe psychotic disorder, with the presence of considerable positive and negative symptoms. Olanzapine has been shown to be very effective in these situations and its use is suggested as first-choice therapy.

Elevated K(+) induces myristoylated alanine-rich C-kinase substrate phosphorylation and phospholipase D activation in glomerulosa cells.

Elevated extracellular potassium concentrations ([K(+)](e)) are known to stimulate aldosterone secretion from adrenal glomerulosa cells in vivo and in vitro. The mechanism is thought to involve depolarization-elicited activation of voltage-dependent calcium channels and an increase in calcium influx. Until now protein kinase C (PKC) was thought not to play a role in the steroidogenic response to elevated [K(+)](e). In this report, we provide evidence in bovine adrenal glomerulosa cells to suggest that elevated [K(+)](e) increases PKC activity, as shown by an enhancement in the phosphorylation of myristoylated alanine-rich C-kinase substrate (MARCKS). Elevated [K(+)](e)-induced MARCKS phosphorylation was delayed and transient and was not the result of a local production of angiotensin II (AngII). MARCKS phosphorylation in response to elevated [K(+)](e) was not accompanied by phosphoinositide hydrolysis but was inhibited by a selective PKC inhibitor. Elevated [K(+)](e) also activated phospholipase D (PLD) in a delayed but sustained manner. We propose that the observed PLD activation mediates the elevated [K(+)](e)-induced MARCKS phosphorylation via PKC, although other factors may modulate this phosphorylation event.

Angiotensin II priming of aldosterone secretion with agents that enhance Ca(2+) influx.

We have previously shown that angiotensin II (AngII) is able to prime, or sensitize, the secretory response of cultured bovine adrenal glomerulosa cells to the Ca(2+) channel agonist, BAY K8644. We examined the ability of AngII to prime glomerulosa cells to an elevated extracellular K(+) level, a physiological agonist that also triggers Ca(2+) influx. K(+) (9 mM) elicited enhanced secretion in AngII-primed cells compared to those with no prior exposure to the hormone, suggesting that AngII can sensitize glomerulosa cells to respond to increases in extracellular K(+). The potential involvement of protein kinase C (PKC) in priming was investigated by determining whether enhanced Ca(2+) influx could maintain the AngII-induced phosphorylation of the endogenous PKC substrate, myristoylated, alanine-rich C kinase substrate (MARCKS). Incubation with the AngII antagonist, saralasin, for 30 min following an AngII exposure reduced the AngII-induced increase in MARCKS phosphorylation. 100 nM BAY K8644 together with saralasin was unable to maintain AngII-stimulated MARCKS phosphorylation. On the other hand, phosphorylation of the steroidogenic acute regulatory (StAR) protein was sustained with saralasin exposure, both in the presence and absence of BAY K8644. This observation suggests that persistent StAR phosphorylation/activation may play a role in priming.

ANPs effect on MARCKS and StAR phosphorylation in agonist-stimulated glomerulosa cells.

Atrial natriuretic peptide (ANP) is a cardiac hormone that inhibits aldosterone secretion induced by all physiologic agonists. The purpose of this study is to explore ANP-induced changes in the phosphorylation of myristoylated alanine-rich C-kinase substrate (MARCKS) and the steroidogenic acute regulatory protein (StAR), in AngII or K(+)-stimulated glomerulosa cells. The data show that ANP completely inhibits the phosphorylation of MARCKS and partially inhibits that of StAR in cells stimulated with K(+). ANP also partially inhibits MARCKS phosphorylation but does not affect StAR phosphorylation in cells stimulated with AngII. These effects appear to be cGMP-independent and at least partially dependent on inhibition of protein kinase C (PKC). To our knowledge, this is the first report of ANP modulating either MARCKS or StAR phosphorylation in [(32)P]-labeled cells. The data also support the hypothesis that ANP inhibits aldosterone secretion acting as a step involved in cholesterol transport to the mitochondria.