PubMed Health⌕ Search

Biomedical subjects

I Wexler

Publications and source records attributed to I Wexler.

17 recordsLinked to original sources
PubMed2004

Antidiabetic effect of novel modulating peptides of G-protein-coupled kinase in experimental models of diabetes.

AIMS/HYPOTHESIS: G-protein-coupled receptor kinases (GRKs) play a key role in agonist-induced desensitisation of G-protein-coupled receptors (GPCRs) that are involved in metabolic regulation and glucose homeostasis. Our aim was to examine whether small peptides derived from the catalytic domain of GRK2 and -3 would ameliorate Type 2 diabetes in three separate animal models of diabetes. METHODS: Synthetic peptides derived from a kinase-substrate interaction site in GRK2/3 were initially screened for their effect on in vitro melanogenesis, a GRK-mediated process. The most effective peptides were administered intraperitoneally, utilising a variety of dosing regimens, to Psammomys obesus gerbils, Zucker diabetic fatty (ZDF) rats, or db/db mice. The metabolic effects of these peptides were assessed by measuring fasting and fed blood glucose levels and glucose tolerance. RESULTS: Two peptides, KRX-683(107) and KRX-683(124), significantly reduced fed-state blood glucose levels in the diabetic Psammomys obesus. In animals treated with KRX-683(124) at a dose of 12.5 mg/kg weekly for 7 weeks, ten of eleven treated animals responded with mean blood glucose significantly lower than controls (4.7+/-0.4 vs 16.8+/-0.8 mmol/l, p</=0.0001). Significant reductions in blood glucose compared with controls were also seen in ZDF rats administered KRX-683(124) and in db/db mice, which had significantly reduced fasting and 2-hour postprandial glucose levels after the treatment. CONCLUSIONS/INTERPRETATION: Sequence-based peptides derived from GRK2/3 have an antidiabetic effect demonstrated in three different animal models of Type 2 diabetes. By modulating GRK2/3 activity, these peptides enhance GPCR-initiated signal transduction, resulting in improved glucose homeostasis. Sequence-based peptide modulation of GRK could prove useful in the treatment of Type 2 diabetes.

Animals↗
PubMed1992

Elimination kinetics of maternally derived thyrotropin receptor-blocking antibodies in a newborn with significant thyrotropin elevation.

OBJECTIVE: To determine the course of maternally derived elevations in thyrotropin-binding inhibitory immunoglobulins in a neonate. DESIGN: Case report. SETTING: University pediatric endocrinology clinic and endocrine immunology laboratory in Ohio. PARTICIPANTS: An infant with elevated thyrotropin levels but near-normal total thyroxine levels, and her mother. INTERVENTIONS: None. MEASUREMENTS/MAIN RESULTS: Thyroid hormone, thyrotropin, and thyrotropin-blocking immunoglobulin concentrations were serially measured in a woman and her infant, who was found to have elevated thyrotropin levels (234 mU/L) and borderline low thyroxine levels (95 nmol/L). As infant thyroxine concentrations remained normal (125 to 145 nmol/L), no thyroxine supplementation was given. Thyrotropin levels decreased concomitantly with thyrotropin-blocking inhibitory immunoglobulin levels, and normalized by day 56 of life. The apparent elimination half-life of thyrotropin-blocking immunoglobulins was 7.5 days. CONCLUSIONS: The observed parallel elimination kinetics suggest that the thyrotropin receptor antibody acts as a thyrotropin antagonist, resulting in compensatory thyrotropin elevations. The duration of such elevations may be predicted on the basis of such elimination.

Autoantibodies↗
PubMed1990

Advances in the electrodiagnosis of nerve injury.

Needle electrode nerve conduction recording is a powerful complement to the traditional techniques of EMG sampling of muscle and surface motor conduction measurements. It enables the electromyographer to assess much more accurately subtle changes in peripheral nerve and nerve root conduction that previously could have gone undetected.

Electrodiagnosis↗
PubMed1983

Sequence of demyelination-remyelination in Guillain-Barré disease.

A detailed investigation of nerve conduction was made in a patient with Guillain-Barré disease. Conduction velocity and configuration of the compound action potential in distal (median), intermediate (tibial) and central (sciatic) nerve segments were studied serially as the patient weakened and then recovered. Demyelination was found to follow a centripetal pattern, occurring first in the most distal portion of nerve and progressing, as the patient weakened, to the spinal root level. Motor and sensory fibres were equally affected although clinically motor weakness predominated. During recovery, central conduction was the first to improve. The pattern of demyelination-remyelination in Guillain-Barré disease appears to be one in which clinical recovery follows remyelination at the spinal root level and in which the first nerve segments to be demyelinated are the last to be remyelinated.

Adult↗
PubMed1977

Withdrawal symptoms in infants with the fetal alcohol syndrome.

Six infants with dysmorphic features of the fetal alcohol syndrome presented with symptoms of withdrawal from alcohol similar to those observed in adults and animals. Symptoms were characterized by irritability, tremors, spontaneous seizures, opisthotonos, and abdominal distention. A comparison of symptoms is made to animal and withdrawal from ethanol and to the neonatal narcotic withdrawal syndrome.

Affective Symptoms↗
PubMed1971

Peripheral nerve activity in response to heating the cat's skin.

1. The sensitivity of the cat hind-limb skin to non-noxious heating was studied. Neural activity was recorded with micro-electrodes from intact multifibre fascicles of the saphenous nerve while the skin was actively heated or passively cooled.2. Moderate warming from indifferent temperatures of 30-34 degrees C to temperatures of 38-39 degrees C produced a reduction in the total rate of firing of the integrated discharge. Firing picked up sharply again at skin temperatures above 39 degrees C. A considerable fraction of the impulse activity elicited above 39 degrees C was carried by C-fibre afferents.3. Prolonged heating to temperatures in excess of 45 degrees C rendered the skin insensitive to further non-noxious heating or to touch.4. The neural response to a step increase in skin temperature consisted of a delayed overshoot and then a steady-state level of firing. Steady-state firing was proportional to the level of skin temperature.5. Nerves whose C-fibre input to the spinal cord had been selectively blocked showed a potentiation of the neural response to skin heating.6. The sensitivity of hind-limb skin to heating, as judged by the character of the multifibre discharge, appears similar to that reported for a highly warm-sensitive region of the nose.

Action Potentials↗
PubMedDate not supplied

The fetal alcohol syndrome: some maternal characteristics.

The characteristics of eight mothers of ten infants born with typical features of the fetal alcohol syndrome (FAS) are presented. These chronic alcoholic mothers have poor obstetric histories, tend to have poor or no prenatal care and may repeat pregnancies which result in infants with FAS. Family planning counseling appears unhelpful.

Child Abuse↗
PubMedDate not supplied

Detection of nerve entrapment during limb lengthening by means of near-nerve recording.

Eight patients undergoing limb lengthening by the Ilizarov method had near-nerve needle electrode conduction studies when they developed clinical signs of nerve entrapment. The near-nerve technique was chosen because it is highly sensitive to configurational changes which appear in the action potential as injury occurs. In 10 out of 13 symptomatic limbs the near-nerve potential was found to be abnormally small and its usually smooth contour had become notched and irregular. In the remaining 3 limbs the potentials were normal initially but became abnormal as further constriction of the nerve took place. Nerve potentials remained normal in size and shape in asymptomatic limbs undergoing lengthening and were not altered by application of the Ilizarov frames themselves. The near-nerve technique proved useful in the early detection of nerve injury in these patients and thus enabled surgical intervention before nerve damage had become permanent.

Adolescent↗