Enhanced insulin absorption in the rabbit airways and lung by sodium dioctyl sulfosuccinate.

The objective of this investigation was to study regional absorption of inhaled insulin together with an enhancer (sodium di-octyl-sulfosuccinate [DOSS]) in the rabbit airways and lung. Insulin was administered with or without DOSS by aerosol inhalation, intratracheal infusion, intranasally, sublingually, and without DOSS intravenously. Blood glucose and plasma levels of insulin were measured during 100 min from the start of administration. Inhalation of insulin (3 U) with 0.25% or 1% DOSS decreased average blood glucose levels significantly more than inhalation of insulin (3 U) without DOSS. Intratracheal administration of 1.5 U of insulin with 0.25% DOSS in 0.3 mL of vehicle decreased the average blood glucose level significantly compared with intratracheal administration of 1.5 U of insulin and no DOSS in 0.3 mL of vehicle and compared with 1.5 U of insulin with 0.25% DOSS in 0.15 mL of vehicle. Intravenous insulin (1.5 U) and inhaled (1.5 U) insulin in 0.25% DOSS decreased average blood glucose levels significantly compared with intratracheal (0.15 mL), intranasal, and sublingual administration of 1.5 U of insulin with 0.25% DOSS. The bioavailability of inhaled insulin (1.5 U) with 0.25% DOSS was estimated to be 16% in comparison with 7% for intratracheally (0.15 mL), 1% intranasally, and 0.8% sublingually administered insulin (1.5 U with 0.25% DOSS), respectively. Inhaled insulin together with the absorption enhancer DOSS decreased the blood glucose level more effectively than insulin given intratracheally, intranasally, or sublingually. The effect on blood glucose reflected the difference in plasma insulin concentration for the different routes of administration.     

Neurochemical aftermath of amateur boxing

PURPOSE: To study young adult elite athletes with age- and sex-matched sedentary controls to assess sex-specific differences for left ventricular (LV) and right ventricular (RV) volumes and mass as well as for LV contraction and relaxation.
MATERIALS AND METHODS: A total of 23 male athletes (mean age 25±4 years, training 22±7 h/week in rowing, swimming, or triathlon) and 20 female athletes (mean age 24±4 years, training 19±5 h/week in rowing, swimming, or triathlon) and age- and sex-matched sedentary controls (21 males/17 females) underwent cardiovascular magnetic resonance (CMR) imaging (1.5 T). Cardiac phase contrast imaging using a black-blood k-space segmented gradient echo sequence was used for analysis of cardiac contraction and relaxation and steady-state free-precession cine images were acquired for determination of cardiac volumes and mass.
RESULTS: Male and female athletes showed similar increases in LV and RV volume and mass indices when compared with controls (ranging between 15% and 42%). No sex-specific differences in training effect on LV and RV volumes, mass indices, and ejection fractions, as well as LV to RV ratios of these volume and mass indices (parameters of balanced LV and RV dilatation and hypertrophy) were observed (all P for interaction >0.05). Similarly, no sex-specific differences in training effect on cardiac contraction and relaxation were found (all P for interaction >0.05).
CONCLUSION: Young adult elite athletes do not show sex-specific adaptive structural and functional changes to exercise training in accordance with the benign nature of the hypertrophy associated with athlete's heart.     

Affective disorder subtyped by psychomotor symptoms, monoamine oxidase, melatonin and cortisol: identification of patients with latent bipolar disorder

A multivariate approach using pattern recognition method was applied on a multivariable data set from patients with affective disorders comprising biological and clinical variables. The depressed patients were rated according to 23 items of the comprehensive psychopathological rating scale (CPRS). Variables of importance were selected and clusters of patients were found by combining monoamine oxidase, melatonin and post-dexamethasone cortisol with symptoms of psychomotor retardation and agitation. Patients were distributed with high scores of agitation in the extreme of one direction and with high scores of retardation in the opposite direction. By using the combined clinical and biological variables, a diagnostic subcategory with latent bipolar disorder was identified. Two clusters of unipolar patients, one with low melatonin and low psychomotor retardation scores, and one with high melatonin and high psychomotor retardation scores, were found. Identification of a patient group with latent bipolar disorder may have potential therapeutic value since bipolar patients should be taken care of by a specialist in psychiatry, avoid tricyclic antidepressant therapy and may be candidates for lithium treatment. Received: 14 October 1997 / Accepted: 19 January 1998     

Placental Transfer of Ampicillin in Man

Abstract: A pharmacokinetic analysis of the foetal/maternal distribution of ampicillin was performed in 25 pregnant women undergoing therapeutic abortion in the middle trimester of pregnancy. The drug was given intravenously before the hysterotomy and the plasma levels were followed during the period up to surgery. When the foetus was removed from the uterus a sample of foetal plasma was taken for ampicillin assay. By means of varying the time between injection and surgery, the ratio between foetal and maternal plasma levels could be determined at various times following the intravenous administration. It was found that the two concentrations became equal after 90 minutes and that the ratio was then steadily increasing for at least 200 minutes. If a two-compartmental pharmacokinetic analysis is made on the basis of the plasma levels in the mother, it shows that a quasi-equilibrium between the central compartment and the tissue compartment is reached already after about 35 minutes following the intravenous injection. Thus, the distribution of ampicillin to the human foetus through the placenta is slower than the distribution of the drug to the maternal tissues. A placental “barrier”seems to exist in the pharmacokinetic sense.     

Pneumatic retinopexy: A critical reappraisal

Pneumatic retinopexy (PR) has been widely advocated for treatment of selected rhegmatogenous retinal detachments: those with small, anterior, superior, retinal breaks and little or no proliferative vitreoretinopathy. It has been suggested that PR is underused and is advantageous because it is an outpatient clinic or office procedure, short in duration, nonincisional, and cost saving – with reduced perioperative morbidity, faster postoperative recovery, better and faster visual recovery, a low rate of complications and a high rate of overall success compared with scleral buckling or pars plana vitrectomy. We reevaluated these advantages to substantiate the effectiveness and efficiency of PR and critically define its role in the treatment of rhegmatogenous retinal detachment. We found that PR has a much higher rate of subsequent reoperation and proliferative vitreoretinopathy than scleral buckling or pars plana vitrectomy for simple, good prognosis rhegmatogenous retinal detachments. PR often involves multiple procedures that largely negates its potential cost savings and subjects the patient to prolonged stress and disability. Scleral buckling rather than PR is ideally suited for simple, good prognosis rhegmatogenous retinal detachments for surgeons who feel comfortable with the technique; alternatively, pars plana vitrectomy is indicated.     

Effects of docosahexaenoic acid-rich n-3 fatty acid supplementation on cytokine release from blood mononuclear leukocytes: the OmegAD study

BACKGROUND: Dietary fish or fish oil rich in n-3 fatty acids (n-3 FAs), eg, docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), ameliorate inflammatory reactions by various mechanisms. Whereas most studies have explored the effects of predominantly EPA-based n-3 FAs preparations, few have addressed the effects of n-3 FAs preparations with DHA as the main FA. OBJECTIVE: The objective was to determine the effects of 6 mo of dietary supplementation with an n-3 FAs preparation rich in DHA on release of cytokines and growth factors from peripheral blood mononuclear cells (PBMCs). DESIGN: In a randomized, double-blind, placebo-controlled trial, 174 Alzheimer disease (AD) patients received daily either 1.7 g DHA and 0.6 g EPA (n-3 FAs group) or placebo for 6 mo. In the present study blood samples were obtained from the 23 first randomized patients, and PBMCs were isolated before and after 6 mo of treatment. RESULTS: Plasma concentrations of DHA and EPA were significantly increased at 6 mo in the n-3 FAs group. This group also showed significant decreases of interleukin (IL)-6, IL-1beta, and granulocyte colony-stimulating factor secretion after stimulation of PBMCs with lipopolysaccharide. Changes in the DHA and EPA concentrations were negatively associated with changes in IL-1beta and IL-6 release for all subjects. Reductions of IL-1beta and IL-6 were also significantly correlated with each other. In contrast, this n-3 FA treatment for 6 mo did not decrease tumor necrosis factor-alpha, IotaL-8, IL-10, and granulocyte-macrophage colony-stimulating factor secretion. CONCLUSION: AD patients treated with DHA-rich n-3 FAs supplementation increased their plasma concentrations of DHA (and EPA), which were associated with reduced release of IL-1beta, IL-6, and granulocyte colony-stimulating factor from PBMCs. This trial was registered at clinicaltrials.gov as NCT00211159.     

Carbamazepine treatment recovered low N-acetylaspartate+N-acetylaspartylglutamate (tNAA) levels in the megencephaly mouse BALB/cByJ-Kv1.1(mceph/mceph)

Megencephaly mice (BALB/cByJ-Kv1.1(mceph/mceph)) display excessive brain growth and seizures related to a mutation within the potassium channel gene Kv1.1 producing a malfunctioning protein. (1)H Magnetic resonance spectroscopy (MRS) provides means to study brain transmitters and metabolites in vivo. We applied MRS to pinpoint differences in hippocampus between mceph/mceph and wild type (wt) mice. Carbamazepine (CBZ) protects against brain overgrowth in mceph/mceph. Therefore, the effects of durable oral CBZ treatment on the MR spectra were investigated. LCModel was used for spectra quantification and multivariate data analysis applied to detect group differences. mceph/mceph mice had lower levels of N-acetylaspartate+N-acetylaspartylglutamate (tNAA) and choline-containing (tCho) compounds compared to wt mice. Glutamate, glutamine, taurine and myo-inositol levels were similar in wt and mceph/mceph. Furthermore, CBZ treatment recovered tCho and tNAA levels in mceph/mceph. Thus, distinct differences in MRS spectra between mceph/mceph and wt mice were depicted and treatment effects of CBZ were monitored using MRS.     

The relationship between somatic and emotional stimuli: a comparison between adolescents with temporomandibular disorders (TMD) and a control group.

The overall purpose of this study was to determine whether adolescents with chronic temporomandibular disorder (TMD) pain are more sensitive to all types of somatic and emotional stimuli compared with a matched healthy control group. Sixty adolescents, 8 boys and 52 girls ranging from 12 to 18 years, participated in the study. Thirty of the subjects exhibited TMD, reporting pain of at least 3 months duration. The age- and gender-matched control group consisted of 30 dental recall patients who reported TMD pain less than once a week. All participants completed a 40-item questionnaire comprising 10 items each of pleasant and aversive qualities crossed with somatic and emotional forms of stimuli. The items, a selection of a broad range of familiar stimuli by a panel of experts, were rated based on intensity of experience (0-10, numerical rating scale). Well-fitting items that formed a valid construct within each of the four domains were selected using Rasch analysis. The results showed that adolescents with TMD pain reported significantly greater sensitivity (p<0.05) to aversive somatic and pleasant somatic stimuli than the controls. The differences between groups for the aversive emotional and pleasant emotional stimuli were non-significant. These findings suggest that chronic TMD pain states in adolescents are accompanied by amplification of bodily, but not purely emotional stimuli and that cognitive systems are implicated, not only an alteration of the nociceptive systems.