NIFEDIPINE BLOCKS ACTH AND CORTISOL RELEASE IN MAN

1. The present study investigated the effect of prior administration of nifedipine on AVP-induced ACTH release in seven normal volunteers. Three protocols were used: 20 mg oral nifedipine; 0.14 pressor units intramuscular (i.m.) per kg bodyweight aqueous AVP; oral nifedipine plus i.m. AVP 90 min later. Plasma ACTH and cortisol were measured at intervals for 2.5 h during each test. 2. The mean peak plasma ACTH and cortisol levels and the mean peak changes from basal in these levels were significantly lower in the nifedipine/AVP test than in the AVP alone test. The integrated area under the cortisol time curve was significantly lower for the nifedipine/AVP test than that for the AVP test alone. Nifedipine alone caused no changes in ACTH or cortisol. 3. Acute administration of oral nifedipine caused an inhibition of AVP-stimulated ACTH and cortisol release in normal humans. This effect may be due to blockade of plasma membrane calcium channels normally activated during AVP stimulation of pituitary corticotrophs.     

Discoid lupus erythematosus at the site of an intradermal injection of killed staphylococcus aureus

A case of chronic discoid lupus erythematosus is described in which there were recurrent relapses following infections, and at the same time repeated `flare ups' at the site of a delayed hypersensitivity reaction to Staphylococcus aureus. The appearance of the injection site changed from that of a typical `tuberculin reaction' to a patch of discoid lypus erythematosus which was confirmed both histologically and by immunofluorescence.     

Neuroimaging of typical and atypical development: a perspective from multiple levels of analysis

To date, research involving functional neuroimaging of typical and atypical development has depended on several assumptions about the postnatal maturation of the brain. We consider evidence from multiple levels of analysis that brings into question these underlying assumptions and advance an alternative view. This alternative view, based on an "interactive specialization" approach to postnatal brain development, indicates that there is a need to: obtain data from early in development; focus more on differences in interregional interactions rather than searching for localized, discrete lesions; examine the temporal dynamics of neural processing; and move away from deficits to image tasks in which atypical participants perform as well as typically developing participants.     

Interactions between the stimulated hypothalamic-pituitary-adrenal axis and leptin in humans

Leptin, produced by adipocytes, has homeostatic effects on body fat mass through inhibition of appetite and stimulation of the sympathetic nervous system. Several studies have reported that high-dose exogenous glucocorticoids increase circulating leptin concentrations in humans. Conversely, leptin has inhibitory effects on the hypothalamic-pituitary-adrenal (HPA) axis, both at the hypothalamic and adrenal levels. We hypothesized that acute hypercortisolism, in the physiological range, may not alter leptin secretion. Four stimuli of the HPA axis were administered to eight healthy male volunteers in a placebo-controlled study. On separate afternoons, in a randomised order, fasting subjects received i.v. injections of saline, naloxone (125 microg/kg); vasopressin (0.0143 IU/kg); naloxone and vasopressin in combination; or insulin (0.15 U/kg; a dose sufficient to induce hypoglycaemia). Plasma concentrations of adrenocorticotrophic hormone (ACTH), cortisol and leptin were measured before and for 120 min after the injection. The cortisol secretory response was greatest after insulin-hypoglycaemia, this response was significantly greater than that following naloxone, naloxone/vasopressin, or vasopressin alone. Despite the cortisol release, leptin concentrations were not increased after any stimulus. Insulin-hypoglycaemia was associated with a decrease in leptin concentration at 60 and 90 min, while naloxone did not alter leptin concentrations. However, basal leptin concentrations were positively correlated with integrated ACTH and cortisol responses to naloxone, but did not correlate with ACTH or cortisol responses to the other stimuli. Thus acute elevations of plasma cortisol, in the physiological range, do not appear to influence plasma leptin concentrations. The fall in plasma leptin concentration after insulin-induced hypoglycaemia may reflect catecholamine secretion after this stimulus.     

Cytotoxic activity screening of Bangladeshi medicinal plant extracts

The cytotoxic activity of 23 crude methanol extracts from 19 Bangladeshi medicinal plants was investigated against healthy mouse fibroblasts (NIH3T3), healthy monkey kidney (VERO) and four human cancer cell lines (gastric, AGS; colon, HT-29; and breast, MCF-7 and MDA-MB-231) using MTT assay. High cytotoxicity across all cell lines tested was exhibited by Aegiceras corniculatum (fruit) and Hymenodictyon excelsum (bark) extracts (IC₅₀ values ranging from 0.0005 to 0.9980 and 0.08 to 0.44 mg/mL, respectively). Fourteen extracts from 11 plant species, namely Clitoria ternatea (flower and leaf), Dillenia indica (leaf), Diospyros peregrina (leaf), Dipterocarpus turbinatus (bark and leaf), Ecbolium viride (leaf), Glinus oppositifolius (whole plant), Gnaphalium luteoalbum (leaf), Jasminum sambac (leaf), Lannea coromandelica (bark and leaf), Mussaenda glabrata (leaf) and Saraca asoca (leaf), were also significantly cytotoxic (IC₅₀ < 1.0 mg/mL) against at least one of the cancer cell lines tested. More selectively, Avicennia alba (leaf), C. ternatea (flower and leaf), Caesalpinia pulcherrima (leaf), E. viride (leaf) and G. oppositifolius (whole plant) showed cytotoxicity only against both of the breast cancer cell lines (MCF-7 and MDA-MB-231). In contrast, C. ternatea (flower and leaf) exhibited high cytotoxic activity against MDA-MB-231 (IC₅₀ values of 0.11 and 0.49 mg/mL, respectively), whereas E. viride and G. oppositifolius whole plant extracts exhibited high activity against MCF-7 cells (IC₅₀ values of 0.06 and 0.15 mg/mL, respectively). The cytotoxic activity test results for 9 of the plant species correlate with their traditional use as anticancer agents, thus making them interesting sources for further drug development.     

Health literacy: Use of the Four Habits Model to improve student pharmacists’ communication

Objective

To assess whether student pharmacists’ communication skills improved using the Four Habits Model (FHM) at the St. Louis College of Pharmacy.

Methods

During the Fall of 2009 and 2010, student pharmacists in the third professional year learned and practiced the FHM. They were given feedback by faculty on three of the four Habits, used the FHM for self and peer assessment, and were formally evaluated on all four Habits during a standardized patient encounter.

Results

Student pharmacist performance significantly improved from baseline during both Fall 2009 and Fall 2010 in the majority of the Habits assessed.

Conclusion

Use of the FHM in pharmacy education can improve a student pharmacists’ ability to display the four Habits of communicating and developing relationships with patients. Tailoring of the FHM to pharmacy encounters will further enhance the utility of this communication framework.

Practice implications

Use of the FHM enhances the measurement and assessment of the relational aspects of student pharmacist–patient communication skills. Consistent use of the FHM over time is likely necessary to fully develop and retain communication skills. The overall goal is to improve patient's health literacy and appropriate medication use by improving communication and the pharmacist–patient relationship.     

Conversational metrics,psychopathological dimensions and self-disturbances in patients with schizophrenia

European Archives of Psychiatry and Clinical Neuroscience - Difficulties in interpersonal communication, including conversational skill impairments, are core features of schizophrenia. However,...     

Use of a glyphosate-based herbicide-induced nephrotoxicity model to investigate a panel of kidney injury biomarkers

Accidental or intentional ingestion of glyphosate surfactant-based herbicides, like Roundup^®, leads to nephrotoxicity as well as death. In this study, a panel of kidney injury biomarkers was evaluated in terms of suitability to detect acute kidney injury and dysfunction. The Roundup^® intoxication model involved oral administration of glyphosate to rats at dose levels of 250, 500, 1200 and 2500 mg/kg. Urinary and plasma biomarker patterns were investigated at 8, 24 and 48 h after dosing. Biomarkers were quantified by absolute concentration; by normalising to urine creatinine; and by calculating the excretion rate. The diagnostic performances of each method in predicting of acute kidney injury were compared. By Receiver Operating Characteristic (ROC) analysis of the selected biomarkers, only urinary kidney injury molecule-1 (KIM-1) best predicted histological changes at 8 h (best cut-off point > 0.00029 μg/ml). Plasma creatinine performed better than other biomarkers at 24 h (best cut-off point > 0.21 mg/dl). Urinary KIM-1 was the best early biomarker of kidney injury in this glyphosate-induced nephrotoxicity model.     

Resistance to RevM10 inhibition reflects a conformational switch in the HIV-1 Rev response element

Nuclear export of certain HIV-1 mRNAs requires an interaction between the viral Rev protein and the Rev response element (RRE), a structured element located in the Env region of its RNA genome. This interaction is an attractive target for both drug design and gene therapy, exemplified by RevM10, a transdominant negative protein that, when introduced into host cells, disrupts viral mRNA export. However, two silent G->A mutations in the RRE (RRE61) confer RevM10 resistance, which prompted us to examine RRE structure using a novel chemical probing strategy. Variations in region III/IV/V of mutant RNAs suggest a stepwise rearrangement to RevM10 resistance. Mass spectrometry was used to directly assess Rev “loading” onto RRE and its variants, indicating that this is unaffected by RNA structural changes. Similarity in chemical footprints with mutant protein implicates additional host factors in RevM10 resistance.