Changes in skeletal muscle contractile properties in streptozocin-induced diabetic rats and role of polyol pathway and hypoinsulinemia

Functional changes in slow-twitch soleus and fast-twitch extensor digitorum longus muscles were assessed after 2 mo of streptozocin-induced diabetes in rats. For soleus, there was a slowing of twitch times both for contraction and relaxation and a reduction of maximum tetanic relaxation rate. There was little effect on strength performance assessed by maximal tetanic tension production. Treatment with the aldose reductase inhibitor ponalrestat largely prevented relaxation defects but had little effect on contraction. For the fast muscle, twitch times were relatively unaffected, but maximum tetanic relaxation rate was reduced. In addition, tetanic tension output decreased. These changes were largely prevented by ponalrestat treatment. The effects of partial insulin therapy were also investigated. This regimen reduced hypoinsulinemia, but sufficient hyperglycemia remained to stimulate the polyol pathway. It prevented the slowing of soleus twitch contraction but had no effect on relaxation. For extensor digitorum longus, insulin produced further deleterious effects on tetanic tension and maximum relaxation rate, which were antagonized by ponalrestat. A 1% dietary myo-inositol supplement had little effect on contractile function in slow or fast muscles. It was concluded that polyol-pathway activity is an important factor underlying skeletal muscle functional changes in diabetes, probably acting through disruption of Ca2+ handling. Hypoinsulinemia was considered a secondary factor causing atrophy, particularly of fast muscles. There was no evidence of effects dependent on neuropathy.     

Role of H3 receptor-mediated signaling in cognition

Inflammation Research -     

Potential for cost economies in guiding therapy in patients with metastatic breast cancer.

Therapeutic response in patients with advanced breast cancer is conventionally assessed with reference to criteria devised by the International Union Against Cancer. Evidence to date suggests, however, that assessments of equivalent quality may be obtained at lower cost from the use of serum markers. The paper presents estimates of potential cost savings resulting from the use of serum markers in place of conventional assessment and argues that the size of these savings merits the establishment of a randomised controlled trial.     

An Inbred Epilepsy-Prone Substrain of BALB/c Mice Shows Absence of the Corpus Callosum, an Abnormal Projection to the Basal Forebrain, and Bilateral Projections to the Thalamus

BALB/c mice lack a corpus callosum in about 11% of the population.Two inbred substrains of BALB/c mice, epilepsy-prone (EP) andepilepsy-resistant (ER), have been examined to determine whetherthese substrains differ in regard to corpus callosum morphology.Further, this study addressed the issue of whether misroutedcortical axons form an aberrant pathway instead of the corpuscallosum. Initial studies that examined fresh brain tissue ofadult animals revealed normal corpora callosa in all ER micebut deficient or absent corpora callosa in all EP mice. Subsequently,Dil crystals were placed in the motor cortices of aldehyde-fixedbrains of 2-week-old animals to investigate cortical projectionsin both inbred substrains of mice. Fluorescent microscopy revealedthat all of the ER animals had normal corpora callosa, whereasall EP animals exhibited either reduced corpora callosa (partiallycallosal) or an absence (acallosal) of this structure. Bothacallosal and partially callosal EP mice displayed an extensive,aberrant projection to the basal forebrain as well as bilateralprojections to midline and intralaminar thalamic nuclei. Thefibers projecting to the basal forebrain arose from the cortex,coursed toward the midline before turning ventrally along themidline, and appeared to terminate in the medial septal nucleusand the nucleus of the diagonal band. ER animals lacked thisaberrant cortical projection to the basal forebrain. Electronmicroscopic results obtained from EP mice indicated that labeledaxons in this aberrant pathway formed axosomatic, axodendritic,and axospinous synapses with the neurons in the medial septal/diagonalband complex. The function of the aberrant projection to thebasal forebrain remains unknown but it may provide an abnormalexcitatory input to a region that provides cholinergic and GABAergicinput to the cerebral cortex and hippocampus. The additionalprojections to midline and contralateral intralaminar thalamicnuclei in EP mice may function to intensify the synchronizationof bilateral discharges.     

The effect of transportation between the recovery room and intensive care unit on postoperative acoustic tumor patients

Cardiovascular changes have been noted to occur during movement from the operating room or recovery room (RR) to the intensive care unit (ICU). This study examined blood pressure changes and related variables during transport from the RR to the ICU in 135 postoperative acoustic tumor patients. Although there was no significant change in blood pressure values from the RR to the ICU, patients with pre-existing hypertension and elevated RR blood pressures were noted to have an increased frequency of postoperative complications. In addition, a relationship was noted between administration of halothane and frequency of postoperative complications. Results highlight the need for nurses not only to monitor, but also closely control postoperative blood pressure in this population.     

Abnormalities of copper in Gilles de la Tourette syndrome

The Gilles de la Tourette syndrome is a disorder whose etiology and pathogenesis are little understood. The number of biochemical abnormalities described in this disorder is minimal. Ten of a total of 80 patients were found to have an abnormally low serum copper. A report is presented on two patients who consented to further detailed investigation and in whom copper radioisotope studies were carried out. Both exhibited abnormalities of copper handling, in that we observed an abnormally fast disappearance of copper from the plasma and an abnormally slow uptake by the liver. The rates of intestinal absorption and urinary excretion were normal. We did not identify an abnormal site of sequestration of the metal in the body.     

Influence of menstrual cycle, parity and oral contraceptive use on steroid hormone receptors in normal breast.

Steroid receptor was assessed immunohistochemically in 158 samples of normal breast for variation through the menstrual cycle. Patterns and intensity of reaction were used in a semi-quantitative scoring system to examine the influence of cycle phase, cycle type, parity and age. The changes in oestrogen receptor for natural cycle and oral contraceptive (OC) cycles indicated down-regulation by progestins. Progesterone receptor did not vary significantly in natural cycles, but increased steadily through OC cycles. This study provides strong evidence that both oestrogen and progesterone influence breast epithelium, but dissimilarities from the endometrium are apparent. The interval since pregnancy had a significant negative effect on frequency and score of oestrogen receptor and score of progesterone receptor. Multivariate analysis established the phase of cycle and OC use as independent significant influences on oestrogen receptor. The interval since pregnancy was an independent significant factor for both oestrogen and progesterone receptor presence.