Intracerebroventricular administration of mouse leptin does not reduce food intake in the chicken

Recently, it has been suggested that leptin plays an important role in regulation of food intake and metabolism in rats and mice, however, the effect of central administration of leptin on food intake in chicks has not been reported. We have investigated the anorexigenic effect of leptin administered by intracerebroventricular (i.c.v.) injection in chicks using mouse leptin, which shows 97% homology to chicken leptin. Three experiments were conducted. After being deprived of food for 3 h, male broiler chicks were administered leptin by i.c.v. injection at dose levels of 0, 0.2, 1.0 and 5.0 microg (Experiment 1) or 0, 2.5 and 5.0 microg (Experiment 2). The birds were allowed free access to the diet for 2 h (Experiment 1) and 24 h (Experiment 2) after treatment. Male Single Comb White Leghorn chicks were used in Experiment 3 and were treated in the same manner as in Experiment 1. In all experiments, central administration of mouse leptin did not influence food intake in the time periods examined. It appears that either mouse leptin does not bind to the chicken leptin receptor or in the chicken brain the leptin receptor may be absent.     

Expression of the poliovirus receptor in intestinal epithelial cells is not sufficient to permit poliovirus replication in the mouse gut

Although the initial site of poliovirus replication in humans is the intestine, previously isolated transgenic mice which carry the human poliovirus receptor (PVR) gene (TgPVR mice), which develop poliomyelitis after intracerebral inoculation, are not susceptible to infection by the oral route. The low levels of PVR expressed in the TgPVR mouse intestine might explain the absence of poliovirus replication at that site. To ascertain whether PVR is the sole determinant of poliovirus susceptibility of the mouse intestine, we have generated transgenic mice by using the promoter for rat intestine fatty acid binding protein to direct PVR expression in mouse gut. Pvr was detected by immunohistochemistry in the enterocytes and M cells of transgenic mouse (TgFABP-PVR) small intestine. Upon oral inoculation with poliovirus, no increase in virus titer was detected in the feces of TgFABP-PVR mice, and no virus replication was observed in the small intestine, although poliovirus replicated in the brain after intracerebral inoculation. The failure of poliovirus to replicate in the TgFABP-PVR mouse small intestine was not due to lack of virus binding sites, because poliovirus could attach to fragments of small intestine from these mice. These results indicate that the inability of poliovirus to replicate in the mouse alimentary tract is not solely due to the absence of virus receptor, and other factors are involved in determining the ability of poliovirus to replicate in the mouse gut.     

Preactivation of B lymphocytes does not enhance mouse mammary tumor virus infection

We investigated whether mouse mammary tumor virus (MMTV) favors preactivated or naive B cells as targets for efficient infection. We have demonstrated previously that MMTV activates B cells upon infection. Here, we show that polyclonal activation of B cells leads instead to lower infection levels and attenuated superantigen-specific T-cell responses in vivo. This indicates that naive small resting B cells are the major targets of MMTV infection and that the activation induced by MMTV is sufficient to allow efficient infection.     

The specificity of immunosuppression by alloantibody in the mouse

The ability of alloantibody to suppress the humoral immune response to transplantation antigens in the mouse has been studied in relation to its specificity. It was found that antibody was able to suppress the cytotoxic antibody response to determinants other than those against which it was directed when there was some common antigenicity between the different H-2 types used for immunising. It was also found that suppression of the response to both parental haplotypes of an F1-hybrid cell could be achieved by antibody to only one parental haplotype, the antibody being made in the other parental strain to avoid any possibility of cross-reactivity. Such nonspecific immunosuppression was not achieved when cells of the two parental strains were administered mixed together.     

Removal of tissue plasminogen activator does not protect against neuronal degeneration in the cerebellum of the weaver mouse

Tissue plasminogen activator (tPA) is a serine protease that has been shown to be involved in neuronal degeneration. Recently, elevated cerebellar tPA has been reported in a naturally occurring mutant mouse, weaver. Weaver mice suffer extensive degeneration of cerebellar granular neurons during development, leading to severe malformation of the cerebellum as well as abnormal behavior (ataxia). The observations that the developing weaver cerebellum displays a 10-fold increase in tPA activity over wild-type and that a serine protease inhibitor was able to rescue weaver granule cells from premature death in culture suggested that tPA might mediate the death of these mutant neurons. We tested this possibility by introducing the weaver mutation into tPA-deficient mice and comparing the weaver phenotype in the presence or absence of tPA. Analysis at 28 days after birth indicates that tPA-deficient weaver mice are indistinguishable from tPA-containing weaver mice in behavior, cerebellar anatomy, histology, and laminin expression (also reported to be increased in weaver). These results suggest that removal of tPA activity from weaver mice does not protect against neuronal degeneration in the cerebellum and, thus, tPA does not appear to mediate this form of cell death.     

Melatonin does not increase IOP significantly in rabbits

Among 3236 pediatric necropsies over 23 years, abnormal position of thymic tissue was recorded in 34 cases. Cardiac anomalies, predominantly those seen in DiGeorge syndrome, were present in 24; 3 had noncardiac anomalies only, 4 had other diseases, and 3 were sudden infant deaths. Mediastinal thymic tissue was absent in 22 cases, small or unilateral in 7, and normal in 5. The maldescended thymic tissue was unilateral in 18, bilateral in 11, and multiple on one or both sides in 5. It was situated near the thyroid gland in 19, lower in the neck in 6, and higher in 9, including 7 medial to the submandibular salivary gland and 1 at the base of the skull. The maldescended tissue approached the size of a normal lobe of thymus in eight and was 2.4 to 0.1 cm in the remainder. Over the same period, in only two cases was no thymic tissue found. Among 68,000 surgical specimens over 40 years, there were 10 cases of ectopic thymus in the neck, including 1 cutaneous and 4 cystic. This frequency of thymic tissue in the neck may explain why lymphoid tissues are sometimes relatively normal in cases of absent mediastinal thymus and behooves a search in the submandibular salivary gland region and higher before diagnosing thymic agenesis.     

Reduced glucose consumption in the curly tail mouse does not initiate the pathogenesis leading to spinal neural tube defects

At embryonic stages of neural tube closure, the mouse embryo exhibits a high rate of glycolysis with glucose as the main energy source. In the curly tail mouse, often used as model system for study of human neural tube defects, a delay in closure of the posterior neuropore (PNP) is proposed to be indirectly caused by a proliferation defect in the caudal region. Because glucose is important for proliferation, we tested glucose uptake in curly tail and control embryos, and in a BALB/c-curly tail recombinant strain. The structure and expression of Glut-1, a glucose transporter molecule that is abundantly present during those embryonic stages and that has been mapped in the region of the major curly tail gene, were also studied; however, no strain differences could be demonstrated. Glucose uptake was determined by measuring glucose depletion from the medium in long-term embryo cultures that encompassed the stages of PNP closure and by measuring accumulation of 3H-deoxyglucose in short-term cultures at the stages of early and final PNP closure. Both approaches indicated a reduced glucose uptake by curly tail and recombinant embryos. Surprisingly, the uptake per cell appeared normal, accompanied by a significantly lower DNA content of the mutant embryos. Therefore, it is unlikely that reduced cell proliferation is caused by a reduction in glucose supply during the pathogenesis of the defects in curly tail embryos. The reduced DNA content as well as the reduced glucose uptake per embryo are likely downstream effects of the aberrant proliferation pattern.     

Pindolol does not act only on 5-HT1A receptors in augmenting antidepressant activity in the mouse forced swimming test

Hypocapnia produces cerebral vasoconstriction. The mechanisms involved in hypocapnia-induced elevation of vascular smooth muscle tone remain unclear. We addressed the hypothesis that, in cerebrovascular smooth muscle, increases in extracellular pH (pHo) cause increases in Ins(1,4,5)P3 and cytosolic calcium ([Ca2+]c). Superfused primary cultures of piglet cerebral microvascular smooth muscle cells were exposed to artificial CSF (aCSF) of control (pHo 7. 4, PCO2 36 mm Hg), metabolic alkalosis (pHo 7.7, PCO2 36 mm Hg), or respiratory alkalosis (pHo 7.7, PCO2 19 mm Hg). Intracellular pH (pHi) and [Ca2+]c were measured, using BCECF and fura-2, respectively, with dual wavelength spectroscopy. Ins(1,4,5)P3 was determined by a protein binding assay. Both metabolic and respiratory acidosis treatments increased pHi from the control value of about 7.2 to 7.35. Metabolic and respiratory alkalosis increased Ins(1,4,5)P3, as we showed previously. Metabolic and respiratory alkalosis increased [Ca2+]c about 80% and 110%, respectively. Neither Ins(1,4,5)P3 nor [Ca2+]c increased in cells treated with aCSF that produced control pHo with increased pHi (7.3). In contrast, when pHo increased (7.7), but pHi was maintained at control (7.2), Ins(1,4,5)P3 increased from 123 pmol/well to 307 pmol/well and [Ca2+]c increased 46%. However, the increase of [Ca2+]c was less than with either respiratory or metabolic alkalosis. Thus, hypocapnia-induced cerebral vasoconstriction could involve production of Ins(1,4,5)P3 with resultant elevation in [Ca2+]c. While the Ins(1,4,5)P3 signal appears to be dependent on an increase in extracellular pH, a role for intracellular pH cannot be completely excluded.     

Prolonged fasting in pediatric outpatients does not cause hypoglycemia

The long-term results after the manipulation and strapping in flexion of selected extension supracondylar fractures of the humerus were evaluated in 43 children. Reduced fractures that were stable when immobilized in approximately 110 degrees of flexion, without producing circulatory obstruction, were treated in this manner. After a minimum review of 4 years, 95 per cent of the children had an excellent or good range of elbow motion and 88 per cent had excellent or good elbow alignment. No child had Volkmann's ischaemic contracture. Five children had cubitus varus which was due to malunion in three, but was unrelated to the treatment of the supracondylar fracture in two children. If these two latter children were excluded then excellent or good alignment was observed in all children who had a Baumann (humerocapitellar) angle of 80 degrees or less at the time of reduction and 84 degrees or less 10 days after the fracture. We concluded that manipulation and strapping in flexion was suitable for approximately 60 per cent of children with isolated displaced supracondylar fractures of the humerus.     

Levodopa does not aggravate postural tremor in Parkinson's disease

Characterization of postural tremor in Parkinson's disease (PD) is incomplete. It was suggested to be an exaggerated physiological tremor and to be enhanced by the action of levodopa. We compared the magnitude of postural tremor to the magnitude of rest tremor and to plasma levodopa levels in 20 PD patients, 10 with stable motor response to oral levodopa, and 10 with the wearing-off phenomenon. Tremor assessment included motor scores of the Unified Parkinson's Disease Rating Scale and accelerometric measurements. Accelerometric data showed that the absolute power of both rest and postural basal dominant tremor frequencies significantly diminished with the increase in plasma levodopa levels and increased with their decrease. Tremor frequencies were also significantly changed by levodopa, which slowed rest tremor and increased postural tremor dominant frequency. This latter, however, did not reach the 8- to 12-Hz frequency band said to be typical of exaggerated physiological tremor. No significant differences between groups were found in their tremor response to levodopa. This study shows that the net postural tremor exhibited by PD patients is improved by levodopa, that levodopa does not augment tremor in the 8- to 12-Hz range, and that this effect is independent of the patient's motor response pattern of oral levodopa.     

The rescue chain does not stop in the hospital

When a patient is saved from a severe illness or accident, his doctor (family practitioner) must care about many problems which are not really medical but also social, psychologic, financial, occupational or political. The interest must be revealed during education and supported by head doctors in hospitals during vocational training years. Therefore, postgraduate training must discuss not only medical problems; the themes mentioned above are just as important.     

Endogenous vasopressin does not mediate hypoxia-induced anapyrexia in rats

The present study was designed to test the hypothesis that arginine vasopressin (AVP) mediates hypoxia-induced anapyrexia. The rectal temperature of awake, unrestrained rats was measured before and after hypoxic hypoxia, AVP-blocker injection, or a combination of the two. Control animals received saline injections of the same volume. Basal body temperature was 36.52 +/- 0.29 degreesC. We observed a significant (P < 0.05) reduction in body temperature of 1. 45 +/- 0.33 degreesC after hypoxia (7% inspired O2), whereas systemic and central injections of AVP V1- and AVP V2-receptor blockers caused no change in body temperature. When intravenous injection of AVP blockers was combined with hypoxia, we observed a reduction in body temperature of 1.49 +/- 0.41 degreesC (V1-receptor blocker) and of 1.30 +/- 0.13 degreesC (V2-receptor blocker), similar to that obtained by application of hypoxia only. Similar results were observed when the blockers were injected intracerebroventricularly. The data indicate that endogenous AVP does not mediate hypoxia-induced anapyrexia in rats.     

Long-acting injectable bromocriptine does not reduce relapse in alcoholics

Dopamine is one of several neurotransmitters that may mediate alcohol intake and dependence. A randomized, double-blind, placebo-controlled international, multicentre study was conducted to assess the effects of a long-acting injectable preparation of bromocriptine, a dopamine agonist, (Parlodel-LAR) in reducing relapse in 366 moderately/severely dependent alcoholics (DSM-III-R), drinking approximately 200 g alcohol (14.5 standard drinks) per day. After detoxification they were randomized to receive six monthly injections of bromocriptine 25 mg (n = 120), bromocriptine 50 mg (n = 124), placebo (n = 122). Brief psychosocial treatment was allowed. At 6 months there were no significant differences between treatment groups in rates of relapse to any drinking or to drinking > or = 5 days per month and > or = 3 drinks per day. Pre-treatment alcohol intake did not determine response. Efficacy ratings by subjects and investigators and adverse events, reported by 51% of subjects, did not differ between treatments. The results of this large study, in which compliance was enhanced by Parlodel-LAR, do not indicate that bromocriptine is efficacious in the maintenance of abstinence or reduced drinking. Possible reasons for the discrepancy between these conclusions and those of some previous clinical trials, in which bromocriptine was reported to reduce symptoms of alcohol withdrawal and dependence, are discussed.     

When target degradation does and does not enhance semantic context effects in word recognition.

Two lexical-decision experiments examined the influence of relatedness proportion (RP, the proportion of word-context–word-target trials sharing a semantic relation) and context-target stimulus onset asynchrony (SOA) on the typically observed interaction between the effects of context and stimulus quality. The standard overadditive interaction of context effects being larger for response times (RTs) to degraded than to nondegraded targets was observed when RP was .50. In contrast, additive effects of context and stimulus quality on RT were observed when RP was .25. These effects were seen at both 200-ms and 800-ms SOAs, even though context effects increased with increasing RP only at the 800-ms SOA. These results (a) undermine the view that expectancy is responsible for producing the standard overadditive Context?×?Stimulus Quality interaction, (b) delineate conditions under which context and stimulus quality have additive and interactive effects on RT, and (c) show that RP has 2 dissociable effects on semantic context effects. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Substrate utilization and maturation of cumulus cell-enclosed mouse oocytes: evidence that pyruvate oxidation does not mediate meiotic induction

This review article describes various quantitation methods for the insulin-regulatable glucose transporter (Glut4). Several methods including reconstituted glucose transport, cytochalasin B binding assays, immunocytochemistry, immunoblots, ELISA, and the more recently developed exofacial labels are discussed. Since Glut4 translocates from an intracellular compartment to the plasma membrane in response to the action of insulin, it is of particular interest to measure Glut4 changes in the membrane fractions. Hence, the measurement of Glut4 commonly involves the isolation of cell membranes using subcellular fractionation in combination with one of the quantitation methods. The limitations of each quantitation method due to the use of subcellular fractionation are discussed in this article. As well, the advantages and disadvantages in terms of isoform specificity and technical difficulties of each method are presented.