Comparative Effects of the Branched-Chain Amino Acids,Leucine, Isoleucine and Valine,on Gastric Emptying,Plasma Glucose,C-Peptide and Glucagon in Healthy Men

(1) Background: Whey protein lowers postprandial blood glucose in health and type 2 diabetes, by stimulating insulin and incretin hormone secretion and slowing gastric emptying. The branched-chain amino acids, leucine, isoleucine and valine, abundant in whey, may mediate the glucoregulatory effects of whey. We investigated the comparative effects of intragastric administration of leucine, isoleucine and valine on the plasma glucose, C-peptide and glucagon responses to and gastric emptying of a mixed-nutrient drink in healthy men. (2) Methods: 15 healthy men (27 ± 3 y) received, on four separate occasions, in double-blind, randomised fashion, either 10 g of leucine, 10 g of isoleucine, 10 g of valine or control, intragastrically, 30 min before a mixed-nutrient drink. Plasma glucose, C-peptide and glucagon concentrations were measured before, and for 2 h following, the drink. Gastric emptying of the drink was quantified using ¹³C-acetate breath-testing. (3) Results: Amino acids alone did not affect plasma glucose or C-peptide, while isoleucine and valine, but not leucine, stimulated glucagon (p < 0.05), compared with control. After the drink, isoleucine and leucine reduced peak plasma glucose compared with both control and valine (all p < 0.05). Neither amino acid affected early (t = 0–30 min) postprandial C-peptide or glucagon. While there was no effect on overall gastric emptying, plasma glucose at t = 30 min correlated with early gastric emptying (p < 0.05). (4) Conclusion: In healthy individuals, leucine and isoleucine lower postprandial blood glucose, at least in part by slowing gastric emptying, while valine does not appear to have an effect, possibly due to glucagon stimulation.     

Response of the ENPP1-Deficient Skeletal Phenotype to Oral Phosphate Supplementation and/or Enzyme Replacement Therapy: Comparative Studies in Humans and Mice

Inactivating mutations in human ecto-nucleotide pyrophosphatase/phosphodiesterase-1 (ENPP1) may result in early-onset osteoporosis (EOOP) in haploinsufficiency and autosomal recessive hypophosphatemic rickets (ARHR2) in homozygous deficiency. ARHR2 patients are frequently treated with phosphate supplementation to ameliorate the rachitic phenotype, but elevating plasma phosphorus concentrations in ARHR2 patients may increase the risk of ectopic calcification without increasing bone mass. To assess the risks and efficacy of conventional ARHR2 therapy, we performed comprehensive evaluations of ARHR2 patients at two academic medical centers and compared their skeletal and renal phenotypes with ENPP1-deficient Enpp1^asj/asj mice on an acceleration diet containing high phosphate treated with recombinant murine Enpp1-Fc. ARHR2 patients treated with conventional therapy demonstrated improvements in rickets, but all adults and one adolescent analyzed continued to exhibit low bone mineral density (BMD). In addition, conventional therapy was associated with the development of medullary nephrocalcinosis in half of the treated patients. Similar to Enpp1^asj/asj mice on normal chow and to patients with mono- and biallelic ENPP1 mutations, 5-week-old Enpp1^asj/asj mice on the high-phosphate diet exhibited lower trabecular bone mass, reduced cortical bone mass, and greater bone fragility. Treating the Enpp1^asj/asj mice with recombinant Enpp1-Fc protein between weeks 2 and 5 normalized trabecular bone mass, normalized or improved bone biomechanical properties, and prevented the development of nephrocalcinosis and renal failure. The data suggest that conventional ARHR2 therapy does not address low BMD inherent in ENPP1 deficiency, and that ENPP1 enzyme replacement may be effective for correcting low bone mass in ARHR2 patients without increasing the risk of nephrocalcinosis. © 2021 American Society for Bone and Mineral Research (ASBMR).     

An Inner-City Asthma Disease Management Initiative

Objectives: The purpose of this study was to evaluate the effects of a recently implemented disease management programme [Asthma Control and Education Program (ACE)] on patient outcomes (clinical and functional) and on resource utilisation in socio-economically disadvantaged (and largely Hispanic) individuals with asthma treated at Hartford Hospital. Design and Setting: Using standardised measures (i.e. the Health Status Questionnaire [HSQ] and the Center for Epidemiologic Studies Depression Scale) and conducting serial assessments the investigators determined: (i) functional status at intake and follow-up; (ii) change in the level of illness severity over time; (iii) patientss’ acquisition of self-management skills; and (iv) the type and frequency of acute care services utilised pre- and post-enrolment in ACE. Patient Population:The study participants consisted of consenting individuals, aged 18 years or older, enrolled in ACE from 1 January 1997 to 30 September 1998. Each individual had a comprehensive intake interview (data collected included clinical and financial status) followed by 3 educational sessions. Results: While only 34.7% (n = 282) of the 813 patients referred from Hartford Hospital to physicians or emergency department services elected to participate in the programme, 60% of participants completed the educational sessions. 73% of these enrollees returned for the 3-month follow-up.On the HSQ, the mean Physical Composite Summary (PCS) scores increased from 33.3 ± 10.01 at baseline to 41.6 ± 11.48 at the 3-month follow up and 45.3 ± 10.30 at the 6-month follow-up. In an analysis using only those patients (n = 50) with HSQ scores at baseline and 3- and 6-month follow-ups, there were statistically significant increases in both the PCS and the Mental Composite Summary scores (p < 0.001).For the 68 patients with severity data at baseline, 3 months and 6 months there was a statistically significant improvement over time (p < 0.001). For example, 4.4% had severe disease at 6 months versus 69.1% at baseline. A subset of 73 patients for whom pre-ACE data were available realised a 37% reduction in emergency department use and a 52% reduction in in-patient visits. Conclusions: The evaluation of disease management programmes requires outcomes data. The results of this study of an asthma disease management programme indicate there was an improvement in overall functioning, illness severity, self-management, and utilisation of inpatient and emergency department services. Although a cause and effect relationship could not be assumed, the results suggest that the disease management model is an effective one for the studied population of inner-city patients, socioeconomically disadvantaged individuals previously identified as high utilisers of healthcare services and as having significant environmental exposures problematic for patients with asthma. As currently designed, however, this programme does not address the healthcare needs of the large number of referred patients who choose not to enrol or the enrollees (40%) who do not complete the education and follow-up sessions.     

Challenges of and strategies for changing prescribing practices of health care providers

Problems related to inappropriate prescribing practices of physicians in general are well recognized. Dietary fluoride supplements have been implicated as one of the contributing factors in an increase in dental fluorosis. Inappropriate prescribing practices of providers have been cited as a major factor in this implication. Numerous studies of physicians and dentists have documented a lack of knowledge and inappropriate prescribing practices regarding fluoride supplements. The purpose of this paper is to identify barriers to changing fluoride-prescribing practices of health care providers and to suggest strategies for implementing change. To increase optimal and appropriate use of fluoride supplements, educational interventions are necessary for all user groups--detail men and women, physicians, dentists, pharmacists, nurse practitioners, dental hygienists, and the public. In addition, environmental supports for the educational activities in the form of policy, regulation, standards of care, and guidelines are recommended for consideration.     

Intravitreal gas injection diminishes hyaluronic acid

OBJECTIVES: To determine if compression of the vitreous by an intraocular gas bubble diminishes the concentration of hyaluronic acid (NaHA). MATERIALS AND METHODS: Eighteen albino rabbits had air, xenon or perfluoroethane (C2F6) injected into the vitreous to displace 12.5% to 90% of the vitreous volume. After the gas was absorbed, the vitreous was analyzed for NaHA by the Carbazole method (1, 13). RESULTS: A 90% displacement diminished the NaHA concentration by 18.6%. Lesser displacements caused a lesser loss, but the differences are not significant. CONCLUSION: Intraocular gas injections, both large and small, reduce the concentration of NaHA and destabilize the vitreous structure.     

Tolerance induction by transdermal glyceryl trinitrate in rats.

Mechanisms of mild glyceryl trinitrate tolerance in rats (transdermal application; 15 mg/day/2 days) were examined in isolated aortic rings contracted with phenylephrine. Tolerance to glyceryl trinitrate was comparable in both endothelium-intact and -denuded vessels; the maximum relaxation decreased to 70-80% and the EC50 increased 3-4-fold. There was minimal cross-tolerance to acetylcholine (1.7-fold increase in EC50) and none to sodium nitroprusside. The results suggest that mild tolerance to glyceryl trinitrate in rats is mediated by mechanisms which are predominantly endothelium-independent and which produce little activation of the cellular mechanism responsible for cross-tolerance.     

The vasa vasorum and angioplasty

Interruption of flow in the vasa vasorum may lead to medial necrosis and aneurysm formation. The purpose of this study was to determine whether angioplasty produces significant alterations in the morphology or blood flow of the vasa vasorum of the dilated artery. The morphology of the canine vasa vasorum was studied before and after angioplasty; in a separate experiment vessel wall blood flow (VWBF) in canine carotid arteries was measured after angioplasty to determine whether physiologic regulation of the blood flow was disrupted by arterial dilation. No morphologic changes could be demonstrated in the vasa vasorum of the dilated artery; however, VWBF was increased by 1194 +/- 215% (mean +/- standard error, p less than 0.01) between 90 and 120 minutes after angioplasty. VWBF in the adjacent nondilated arterial segment was also increased (720 +/- 177% between 10-30 minutes, p less than 0.01) but returned toward normal after 60 minutes. Adenosine caused a "paradoxical" decrease in VWBF (p less than 0.05) of the dilated arterial segment while causing increased VWBF (p less than 0.05) in the thoracic aorta. Angioplasty appears to produce persistent hyperemia in the dilated arterial wall. A paradoxical response to adenosine suggests that vasa vasorum in the dilated arterial segment are maximally vasodilated. This may be due to mechanical disruption of vasomotor tone or to release of vasoactive substances.     

New flavonoid-glycosides from Crataegus monogyna and Crataegus pentagyna

From the leaves and flowers of Crataegus monogyna and C. Pentagyna six new flavonoid-C- and O-glycosides respectively have been isolated and identified as 2'-O-rhamnosyl-orientin, 2'-O-rhamnosyl-isoorientin, 2'-O-rhamnosyl-isovitexin, rutin, spiraeosid, 8-methoxy-k?mpferol and 8-methoxy-k?mpferol-3-O-glucoside. The structure of O-rhamnosyl-vitexin and O-acetyl-O-rhamnosyl-vitexin isolated previously, have been elucidated unambigiously mainly by NMR- and MS-spectroscopy.     

Comparative trial of mexiletine and lignocaine in the treatment of early ventricular tachyarrhythmias after acute myocardial infarction

The antiarrhythmic effects of intravenously administered lignocaine and mexiletine were compared over a period of 48 hr in a randomized trial on 24 patients who developed ventricular tachyarrhythmias within 48 hr of the onset of acute myocardial infarction. Mexiletine was given as an initial bolus of 200 mg, followed by an infusion of 1 mg/min reduced to 0.5 mg/min after 1 hr. Lignocaine was given as a bolus of 100 mg, followed by an infusion of 3 mg/min reduced to 2 mg/min after 1 hr. Plasma levels of mexiletine, lignocaine, and monoethylglycinexylidide were monitored. The frequency of "complex" ventricular tachyarrhythmias was significantly lower in the mexiletine-treated group. This group of patients also had significantly fewer ventricular extrasystoles than those receiving lignocaine, the difference being most marked during the second 24 hr of treatment. Too few episodes of ventricular fibrillation occurred for statistical comment. The greater efficacy of mexiletine was not associated with increased drug toxicity.     

The incidence of known diabetics among U.S. Army active duty dental patients

Diabetes affects an estimated 16 million Americans. The purpose of this study was to determine the incidence of known diabetes among active duty soldiers by reviewing medications dispensed for diabetes at a large military installation. This study was conducted from July 31, 1997, through August 1, 1998. Fifty-eight (0.18%) members of the total active duty male population of 32,593 had been dispensed diabetes medications, whereas 43 (0.48%) members of the total female active duty population of 8,898 had been dispensed medications for diabetes. Gestational diabetes was the cause for 88.37% of the total active duty females dispensed diabetic medication at Fort Hood, Texas. The female-to-male ratio for diabetes was 2.7:1. Diabetics made up 0.27% of the total population.