Immunoglobulin-like domain containing receptor 1 mediates fat-stimulated cholecystokinin secretion

Cholecystokinin (CCK) is a satiety hormone produced by discrete enteroendocrine cells scattered among absorptive cells of the small intestine. CCK is released into blood following a meal; however, the mechanisms inducing hormone secretion are largely unknown. Ingested fat is the major stimulant of CCK secretion. We recently identified a novel member of the lipoprotein remnant receptor family known as immunoglobulin-like domain containing receptor 1 (ILDR1) in intestinal CCK cells and postulated that this receptor conveyed the signal for fat-stimulated CCK secretion. In the intestine, ILDR1 is expressed exclusively in CCK cells. Orogastric administration of fatty acids elevated blood levels of CCK in wild-type mice but not Ildr1-deficient mice, although the CCK secretory response to trypsin inhibitor was retained. The uptake of fluorescently labeled lipoproteins in ILDR1-transfected CHO cells and release of CCK from isolated intestinal cells required a unique combination of fatty acid plus HDL. CCK secretion secondary to ILDR1 activation was associated with increased [Ca²⁺]_i, consistent with regulated hormone release. These findings demonstrate that ILDR1 regulates CCK release through a mechanism dependent on fatty acids and lipoproteins and that absorbed fatty acids regulate gastrointestinal hormone secretion.     

Adaptation of the health literacy universal precautions toolkit for rheumatology and cardiology – Applications for pharmacy professionals to improve self-management and outcomes in patients with chronic disease

Over a decade of research in health literacy has provided evidence of strong links between literacy skills of patients and health outcomes. At the same time, numerous studies have yielded insight into efficacious action that health providers can take to mitigate the negative effects of limited literacy. This small study focuses on the adaptation, review and use of two new health literacy toolkits for health professionals who work with patients with two of the most prevalent chronic conditions, arthritis and cardiovascular disease. Pharmacists have a key role in communicating with patients and caregivers about various aspects of disease self-management, which frequently includes appropriate use of medications. Participating pharmacists and staff offered suggestions that helped shape revisions and reported positive experiences with brown bag events, suggestions for approaches with patients managing chronic diseases, and with concrete examples related to several medicines [such as Warfarin^©] as well as to common problems [such as inability to afford needed medicine]. Although not yet tested in community pharmacy sites, these publically available toolkits can inform professionals and staff and offer insights for communication improvement.     

Intravenous streptokinase in the management of a subset of patients with unstable angina: a randomized controlled trial

We report the results of a randomized controlled trial of intravenous streptokinase in a subset of patients with unstable angina. Seventy-six patients were admitted with prolonged (more than 20 minutes) angina at rest of less than 3 weeks onset. Fifty-two patients continued to have more than 3 episodes of prolonged angina in 48 hours on medical therapy with metoprolol, isosorbide dinitrate, nifedipine and intravenous nitroglycerin. Forty-eight patients consented to enter the study and were randomized into two groups. The first group, of 24 patients, received 1.5 million units of streptokinase infusion and the second group, also of 24 patients, received a placebo. Pain relief within 48 hours was achieved in 19/24 (79.1%) patients after streptokinase infusion as compared to 9/24 (37.5%) of the controls (P less than 0.05). Approximately 90% (17/19) of patients responding to streptokinase therapy were relieved of chest pain within the first six hours as against none in the controls. The incidence of acute myocardial infarction within six months was 12.5% (3/24) in those receiving streptokinase and 25% (6/24) in the controls. Mortality at six months stood at 8.33% (2/24) in the treated patients and 16.6% (4/24) in the controls. Intravenous streptokinase thus appears to be of benefit in patients with angina at rest of recent onset which does not respond to conventional medical therapy.     

NMR based CSF metabolomics in tuberculous meningitis: correlation with clinical and MRI findings

Metabolic Brain Disease - We report the potential role of 1H Nuclear Magnetic Resonance (NMR) based metabolomics in tuberculous meningitis (TBM). We also correlate the significant metabolites with...     

Correlation of symptoms with occurrence of paroxysmal supraventricular tachycardia or atrial fibrillation: a transtelephonic monitoring study. The Flecainide Supraventricular Tachycardia Study Group.

The purpose of this study was to determine whether symptoms recorded at the time of transtelephonic ECG monitoring (TTEM) correlate with attacks of paroxysmal supraventricular tachycardia (PSVT) or paroxysmal atrial fibrillation (PAF). We studied 113 patients with these arrhythmias who made a total of 3319 TTEM calls during their participation in double-blind, placebo-controlled, crossover, multicenter trials of flecainide therapy. Among 49 patients with PSVT, 62.7% of symptomatic calls were associated with ECG-documented PSVT as compared with 6.8% of asymptomatic calls (p less than 0.001). Similarly, among 69 patients with PAF, 69% of symptomatic calls were associated with ECG-documented PAF compared with 10.6% of asymptomatic calls (p less than 0.001). Both in patients with PSVT and PAF, an attack of PSVT or PAF could be documented by ECG in more than 70% of the calls when patients complained of tachycardia, increased sweating, or dyspnea. The sensitivity of a symptomatic call was 91% for PSVT and 89% for PAF, and it was not influenced by flecainide therapy. However, flecainide therapy was associated with a decrease in the positive predictive value of symptomatic TTEM calls and an increase in false positive TTEM transmissions. We conclude that in patients with symptomatic PSVT or PAF, there is a temporal relationship between symptoms and the occurrence of ECG-documented attacks of PSVT or PAF. However, sole reliance should not be placed on the presence or absence of symptoms as a measure of drug failure or efficacy, and it is important to document the cardiac rhythm by TTEM at the time symptoms are recorded.     

Frequency and significance of induced sustained ventricular tachycardia or fibrillation two weeks after acute myocardial infarction

Electrophysiologic study, 24-hour ambulatory electrocardiographic monitoring, treadmill exercise test and angiographic evaluations were performed in 45 patients 14 +/- 3 days (mean +/- standard deviation) after acute myocardial infarction. Electrophysiologic study protocol included burst ventricular pacing and 1 to 3 ventricular extrastimuli at 2 cycle lengths from right ventricular apex, right ventricular outflow and left ventricle. Sustained monomorphic ventricular tachycardia (VT) (13 patients) or ventricular fibrillation (VF) (7 patients) was induced in 20 patients (44%) (group I). In these 20 patients, VT/VF was inducible with 2 extrastimuli in 10 patients, 3 extrastimuli in 9 patients and burst pacing in 1 patient. In the remaining 25 patients (56%), induction of no fewer than 7 ventricular beats were noted (group II). Severe left ventricular (LV) wall motion abnormalities occurred in 70% of group I patients and 22% of group II patients (p less than 0.005). There was no difference in the site of infarction, frequency and grade of ventricular ectopic rhythm on ambulatory electrocardiographic monitoring, double product on submaximal exercise, LV ejection fraction, and number of obstructed coronary arteries (70% or greater) (p greater than 0.1) between group I and group II patients. During a mean follow-up of 10 +/- 3 months, 1 patient in each group died suddenly, and in 1 group I patient spontaneous sustained VT developed which was identical in morphologic configuration to that induced during electrophysiologic study. In conclusion, electrical induction of sustained VT or VF during electrophysiologic study is common in patients 2 weeks after acute myocardial infarction.(ABSTRACT TRUNCATED AT 250 WORDS)     

Is β-cell failure in type 2 diabetes mellitus reversible?

BACKGROUND:

In the UK Prospective Diabetes Study (UKPDS), many subjects maintained glycemic goal (HbA_1c < 7.0%) at 9 years, showing that β-cell function was preserved and that the initial decline in β-cell function recovered with sulphonylureas. Moreover, obese subjects using high daily doses of insulin for several years rarely require insulin or oral hypoglycemic agents to maintain their glycemic goal following weight loss achieved by gastric bypass surgery. Thus, declining β-cell function during the course of type 2 diabetes mellitus (T2DM) is neither universal nor permanent.

OBJECTIVE:

To assess β-cell function in morbidly obese subjects before insulin withdrawal and on attaining the glycemic goal with weight loss and oral agents.

MATERIALS AND METHODS:

Serum C-peptide (CPEP) and glucose (G) concentrations were determined up to 180 min during an oral glucose tolerance test (OGTT) with 75 glucose in 10 obese men with T2DM, before insulin withdrawal, and on achieving the glycemic goal with metformin, glimepiride, and weight loss. Ten age-matched healthy men participated as controls. Cumulative responses (CR) of CPEP and G were calculated by adding differences between the level at each time-period during OGTT and fasting (F) concentration. β-Cell function was expressed as the FCPEP as well as the insulinogenic index (CRCPEP/CRG). Insulin sensitivity was determined as FCEP × FG.

RESULTS:

FCPEP was decreased, though still present, prior to insulin withdrawal. Moreover, on attaining the glycemic goal over 6-9 months, FCPEP, CRPEP/CRG, and FCPEP × FG improved markedly (P < 0.001).

CONCLUSION:

Decline in β-cell function in morbidly obese T2DM may not be progressive and is reversible on improving insulin sensitivity and on eliminating the inhibition by exogenous insulin.     

Day to day reproducibility of electrically inducible ventricular arrhythmias in survivors of acute myocardial infarction

Day to day reproducibility of the response to programmed ventricular stimulation has not been evaluated in survivors of acute myocardial infarction. Programmed ventricular stimulation was performed prospectively on 2 consecutive days in 56 patients on an average of 12 +/- 5 days (range 7 to 29) after an acute myocardial infarction. No patient had a history of documented or suspected sustained ventricular tachycardia or fibrillation occurring greater than 48 h after infarction. During initial programmed ventricular stimulation, 21 patients had induction of sustained ventricular tachycardia or fibrillation (Group I), and 35 patients had induction of either nonsustained ventricular tachycardia or no ventricular tachycardia (Group II). Repeat programmed ventricular stimulation in Group I patients induced sustained ventricular tachycardia or fibrillation in 16 of 21 patients (reproducibility 76%); the maximal induced response in the other 5 patients was nonsustained ventricular tachycardia in 2 patients and fewer than six repetitive ventricular responses in 3 patients. The day to day reproducibility was significantly higher for inducible sustained ventricular tachycardia of cycle length greater than or equal to 240 ms compared with rapid sustained ventricular tachycardia of cycle length less than 240 ms (100% versus 44%, p less than 0.009) or ventricular fibrillation (100% versus 43%, p less than 0.009). Repeat programmed ventricular stimulation in Group II patients did not induce sustained ventricular arrhythmias in 31 of 35 patients (reproducibility 89%). Thus, in survivors of acute myocardial infarction, inducible slow sustained ventricular tachycardia was a highly reproducible finding, whereas inducibility of rapid sustained ventricular tachycardia and ventricular fibrillation showed a significant day to day variability.(ABSTRACT TRUNCATED AT 250 WORDS)     

Emerging Treatments in Episodic Migraine

Purpose of Review

The purpose of this review is to evaluate and describe recent and emerging treatment options for episodic migraine.

Recent Findings

Recent advances have been made in better understanding the pathophysiology of migraine, which has led to further investigation of potential new pharmacologic and non-pharmacologic treatment options.

Summary

A number of new medications are emerging for the acute and preventive treatment of migraine, including CGRP monoclonal antibodies, CGRP receptor antagonists, serotonin 5-HT_1F agonists, and PACAP receptor monoclonal antibodies. Additionally, newer studies on existing non-invasive neuromodulation devices including transcranial magnetic stimulation, supraorbital transcutaneous nerve stimulation, and transcutaneous vagus nerve stimulation have recently received FDA approval for use in migraine. Neuromodulation devices including percutaneous mastoid electrical stimulation, non-painful remote electrical stimulation, and caloric vestibular stimulation are undergoing further investigation and have shown promising results thus far. These new developments are expected to contribute to better treatment and decreased disability in migraine.