Genetic variants of human erythrocyte glucose 6-phosphate dehydrogenase: new variants in West Africa characterized by column chromatography

Seven calves seven to 30 days of age were given Mycoplasma bovis antigen by different routes. Immunization was in two phases. The first consisted of single or multiple SC, IV or oral doses of antigen for two to four weeks. The second phase consisted of multiple SC or ID injections given from the eighth to the 19th week. The experiment was terminated at 26 weeks. Antibody titers were followed by indirect hemagglutination, growth inhibition and tetrazolium reduction inhibition. Total serum protein, protein fractions and IgG and IgM concentrations were determined in serums of one calf and the distribution of indirect hemagglutination antibodies in IgG and IgM classes were determined in serums of two of the calves. Indirect hemagglutination titers of 1280 and peak titers of >20,480 occurred after the first and second phases respectively. There was no relationship between total serum IgG or IgM concentrations and indirect hemagglutination titers. In one calf given M. bovis antigen in one dose SC and five weekly doses IV in phase I, indirect hemagglutination antibodies appeared in IgM within one week and IgG by four weeks, IgG antibody activity rose steadily until the 17th week but declined at the 26th week, whereas IgM activity after the initial rise dropped at the 13th week but rose even higher as a result of second phase ID injections. Another calf given six weekly IV doses of M. bovis antigen in phase I developed indirect hemagglutination antibodies in IgM peaking at four weeks then declining but with no IgG response. Activity in both IgM and IgG occurred after the second phase. Growth inhibition antibodies were found only on two occasions in one calf serum and tetrazolium reduction inhibition activity when tested never gave titres exceeding 1:32.     

Chemical sympathectomy and two-way escape and avoidance learning in the rat.

Reports 6 studies with male hooded Wistar rats on the effects of 2,4,5-trihydroxyphenylethylamine (6-hydroxydopamine) on 2-way escape and avoidance learning. Ss were tested on either escape or avoidance learning at 80 days of age after chemical sympathectomy at birth or 40 or 80 days of age. Neonatal and chronic sympathectomy (at 40 days), but not acute sympathectomy (at 80 days), resulted in depressed escape learning. Avoidance learning was affected by neonatal sympathectomy and partially by acute sympathectomy. Results have implications for the role of the autonomic nervous system in escape-avoidance learning. (27 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Safety and pharmacokinetics of an intramuscular humanized monoclonal antibody to respiratory syncytial virus in premature infants and infants with bronchopulmonary dysplasia. The MEDI-493 Study Group

BACKGROUND: Respiratory syncytial virus (RSV) is the leading cause of lower respiratory disease in infants and children. MEDI-493 (palivizumab, Synagis) is a humanized monoclonal IgG1 antibody to the fusion protein of RSV, and it is highly active in vitro against RSV A and B strains. OBJECTIVE: To describe the safety, tolerance, immunogenicity and pharmacokinetics of monthly intramuscular injections of MEDI-493 among premature infants and children with bronchopulmonary dysplasia and to compare these data with information previously obtained with intravenous dosing. DESIGN: A Phase I/II multicenter, open label, escalating dose clinical trial. PATIENT POPULATION AND DOSING REGIMEN: Children (n=65) born prematurely at < or =35 weeks of gestation who were < or =6 months of age (n=41) and children with bronchopulmonary dysplasia who were < or =24 months of age (n=24) were enrolled. From 1 to 5 monthly injections were given at doses of 5 mg/kg (n=11), 10 mg/kg (n=6) and 15 mg/kg (n=48). Serum was collected before administration of each dose, 30 days after the last dose, and 2, 7 and 14 days after the first and second doses for measurement of MEDI-493 concentrations by enzyme-linked immunosorbent assay. RESULTS: The pharmacokinetics of MEDI-493 were similar to those of other human IgG1 antibodies. Mean serum MEDI-493 concentrations were 91.1 microg/ml (range, 52.3 to 174.0) 2 days after the initial dose of 15 mg/kg and 49.2 microg/ml (range, 13.5 to 132.0) at 30 days. Monthly dosing of 15 mg/kg maintained mean trough concentrations of approximately 70 microg/ml. These concentrations were similar to previously published trough concentrations after i.v. administration. MEDI-493 injections were well-tolerated. Only three children had adverse events judged to be possibly related to MEDI-493. Ten children had transient, low titer anti-MEDI-493 binding titers (1:10 to 1:40) which were not associated with a pattern of specific adverse events or alterations of MEDI-493 concentrations. Two patients in the 5-mg/kg dose group were hospitalized for RSV; no RSV hospitalizations were found in the higher dose groups. CONCLUSIONS: MEDI-493 was safe and well-tolerated. Monthly intramuscular doses of 15 mg/kg maintained mean trough serum concentrations that were above 40 microg/ml (the value associated with 99% reduction of pulmonary RSV in the cotton rat model). These concentrations were similar to those previously reported with i.v. administration of MEDI-493.     

Effects of sympathetic inhibition on receptive, proceptive, and rejection behaviors in the female rat

The present investigation was designed to examine the effects of sympathetic nervous system (SNS) inhibition on sexual behavior in ovariectomized, steroid-treated female rats. Clonidine, an alpha2-adrenergic agonist, guanethidine, a postganglionic noradrenergic blocker, and naphazoline, an alpha2-adrenoreceptor agonist were used to inhibit SNS activity. Intraperitoneal injections of either 33 micrograms/ml or 66 micrograms/ml clonidine significantly decreased receptive (lordosis) and proceptive (ear wiggles) behaviors and significantly increased rejection behaviors (vocalization, kicking, boxing). Either 25 mg/ml or 50 mg/ml guanethidine significantly decreased receptive and proceptive behavior and had no significant effect on rejection behaviors. Naphazoline significantly inhibited lordosis behavior at either 5 mg/ml or 10 mg/ml doses, significantly inhibited proceptive behavior at 5 mg/ml, and had no significant effect on rejection behaviors. These findings support the hypothesis that SNS inhibition decreases sexual activity in the female rat.     

The effect of octreotide on wound healing: an in vitro and in vivo experimental study

OBJECTIVE: To investigate the effect of octreotide on wound healing. DESIGN: Experimental studies in vitro and in rats. SETTING: Teaching hospital, Israel. MATERIAL: Cultured human diploid fetal fibroblasts, and 36 male Wistar rats. INTERVENTIONS: Octreotide was added to cultures of fibroblasts in doses of 2, 10, 30, 60 and 120 ng/ml and fibroblasts were counted after 2, 4, and 6 days. Intestinal anastomoses were made in 36 rats. Rats in the octreotide group (n = 18) were given subcutaneous injections of 0.25 microg/kg twice daily and 6 rats were killed at 3, 7, and 14 days. The control group were given injections of saline. Anastomotic bursting pressures and hydroxyproline content were measured at each of the three times. MAIN OUTCOME MEASURES: Fibroblast counts, anastomotic bursting pressures, and hydroxyproline concentrations. RESULTS: Octreotide did not inhibit fibroblast proliferation in any of the doses at any of the time periods. The anastomotic bursting pressure was slightly higher in the octreotide group at each of the time points, but not significantly so, and there was no difference in hydroxyproline content between the octreotide and control groups. Octreotide did not inhibit wound healing either in vitro or in vivo.     

Changes in the level of selected laboratory parameters in blood after implantation of chitosan fibers

The tests were carried out on rats of the Wistar tribe to the peritoneal cavity of which chitosan fibres were implanted. The blood for the tests was taken in 3, 7, 14, 30 and 60 days after the implantation. In the blood hematological, biochemical and clotting system parameters were marked. Moreover they made pathomorphological tests of the tissues surrounding the implanted material and laboratory and biological tests of aqueous extracts from chitosan fibres. The shown quantitative changes in the level of the marked parameters of blood to the 14th day of observation are connected mainly with toxicity of chitosan fibres, whereas to the 30th and 60th day-with the process of biodegradation and resorption of collagenous fibres.     

Natural resistance to Marek''s disease at hatching in chickens lacking maternal antibody, and relationship between this early resistance and resistance acquired with age

A double-blind cross-over trial was conducted with 20 healthy paid volunteers for the evaluation of the subacute effects of chlorpromazine (CPZ) and sulpiride, in oral doses used for anxious outpatients, on psychomotor skills related to driving. Psychomotor performance was measured on the 7th and 14th days of treatment at 30, 90 and 150 min after the intake of 0.5 g/kg of an alcoholic or placebo drink. After the neuroleptics alone, reaction and coordination skills, but not attention, were slightly impaired, CPZ differing significantly from the placebo on the 14th day. Both drugs interacted additively with alcohol. The combined administration of CPZ and alcohol led to inaccuracy, a slowing of reactions and impaired proprioception and coordination. The combination of sulpiride and alcohol increased the error rate in the choice reaction test and impaired coordination in the coordination test driven at a free speed. It is concluded that the psychomotor decrement that occurs after 2 weeks of treatment with small doses of CPZ may effect the ability to control a motor vehicle. The concurrent administration of alcohol during treatment with CPZ or sulpiride may cause some extra risk in traffic or occupational life.     

Attenuated glutamate release during ischemia in ethanol-administered gerbils

Previous studies have found an association between prior ethanol consumption and aggravated stroke outcome. Gerbils were intermittently given ethanol injections (s.c.) for 21 days at doses of 1 and 4 g/kg. After cessation of injections and appropriate weight gain, subjects underwent bilateral carotid occlusion while amino acid neurotransmitter levels in the hippocampus were monitored. Both the low and high dose ethanol groups demonstrated significantly decreased glutamate release compared with saline-treated controls during ischemia (p < 0.05). These results are consistent with a long-lasting ethanol-induced decrease in synaptic density in the hippocampus. That no intergroup differences on histological or neurobehavioral measures was found may suggest a functional dissociation of glutaminergic involvement in the pathogenesis of aggravated stroke outcome with alcoholism.     

Bioavailability and pharmacokinetics of beta-methyldigoxin after multiple oral and intravenous doses

To obtain true half lives, glycoside elimination from six healthy subjects was studied for 14 days after multiple intravenous doses or oral administration of a daily maintenance dose of beta-methyldigoxin 0.3 mg. After oral or intravenous administration of beta-methyldigoxin ceased, the plasma concentrations declined from the 14th to the 16th days with a half life of 1.7 days. From the 16th to the 20th day a change from a shorter to a longer half life of 2.8 and 2.9 days was observed. Similar half lives were found in urine: after the last dose the initial slope from the 14th to the 16th day had a half life of 1.8 days, and the terminal slope had one of 3.2 days. The results indicate release of the glycoside from slowly equilibrating tissues.     

Role of functional overloading of the maxillo-dental system in the development of radiation osteomyelitis

The authors present a work intended to assess the effects of lumbar sympathectomy using radioactive microspheres. These contain 99mTe and are injected into the femoral artery. The distribution of radioactivity is then measured at the lower limb with a gamma camera linked to a computer. Seventeen patients were tested before and after lumbar sympathectomy. It appears from this short series that lumbar sympathectomy causes a redistribution of the radioactive material directed towards the extremities, mainly the feet.     

Inhibition of morphine-induced tolerance and dependence by a benzodiazepine receptor agonist midazolam in the rat

We investigated whether midazolam administration influenced morphine-induced antinociception and tolerance and dependence in the rat. Antinociception was assessed by the tail-flick (TF) and the hot-plate test (HP 52 degrees C). Morphine tolerance developed after daily single injections of morphine for 11 days. The effect of midazolam on morphine-induced antinociception and tolerance was assessed by giving daily injections of various doses of midazolam for 11 days. The first injection of saline or midazolam was given intraperitoneally and 30 min later morphine (10 mg/kg body weight) was administered subcutaneously. Antinociception was monitored by measuring TF and HP latencies 60 min after the second injection. Midazolam was injected at four different concentrations: 0.03, 0.1, 0.3, and 3 mg/kg body weight. Chronic administration of morphine resulted in the development of tolerance to antinociception in both TF and HP tests, with rats exhibiting baseline antinociception on Day 9. Animals treated with midazolam alone showed little antinociception on Days 3-9. However, midazolam administration in morphine-treated animals attenuated morphine-induced tolerance to antinociception on Days 1-11 as measured by the tail-flick test. Midazolam also decreased the jumping behavior following naloxone injections in morphine-dependent rats. These results suggest that midazolam may prolong the effects of morphine by delaying morphine-induced development of tolerance to antinociception. Midazolam also attenuated a decrease in weight gain induced by chronic injections of morphine.     

Season of birth and Alzheimer''s disease: a population-based study in Saguenay-Lac-St-Jean/Québec (IMAGE Project)

The ontogenic expression of progesterone and estrogen receptors (PR and ER) and effect of estrogen on these receptors were investigated immunohistochemically in rat uterus from the day of birth ( = 0 day) to 30 days of age. Uterine epithelial and stromal cells showed a negative PR immunoreaction at 0 day. The PR in the epithelial cell nuclei appeared by 5 days, while the stromal cells showed a negative PR reaction until 12 days. The staining of the stromal cells appeared from 12 to 15 days. In both the epithelial and stromal cells, the initiation of the PR appearance was not affected by ovariectomy performed at 0 day or 5 days prior to the appearance of PR in the epithelial and stromal cells. Estrogen injections from 0 day failed to initiate the appearance of PR in the epithelial cells, regardless of doses of estradiol-17 beta (0.1, 1 and 10 micrograms daily), but induced PR in the stromal cells. The staining of ER appeared at 5 days in the epithelial cells and at 1 day in the stromal cells, respectively. ER appeared after 2-3 daily injections of estrogen from 0 day depending upon the doses. These results suggest that steroid hormones secreted from neonatal ovary do not play any important role in ontogenic expression of PR during the postnatal uterine maturation.     

Morphofunctional changes in the cat pancreas after resection of the jejunum

Experiments with resection of the jejunum were carried out in male cats. Changes in the structure of the exocrine and endocrine portion of the organ were studied histologically. Amylase and lipase activity and sugar content were determined in the blood. Hypertrophy and hyperplasia were discovered in the acinar portion of the gland in the course of 1 to 14 days of the experiment; in the endocrine portion it was present for 7 to 30 days. On the 21st, 30th and 180th days of the experiment an atrophic process was observed in the acinar cells; in the island cells it was seen on the 180th day only. The function of the exocrine portion of the pancreas was disturbed on the 2nd-21st days of the experiment, while that of the endocrine portion-on the 7th day only.     

The effect of cervical sympathectomy on the pituitary and pineal endocrine system

It was reported previously that continuous exposure to light in male rats increased serum luteinizing hormone (LH) and bilateral cervical sympathectomy inhibited such a change. In the present report, to examine the effect of cervical sympathectomy on the pineal endocrine function, 30 male rats were assigned to five groups. The control (C) group and the light (L) group underwent sham sympathectomy as well as sham pinealectomy. The sympathectomy (S) group underwent sympathectomy and sham pinealectomy. The pinealectomy (P) group and pinealectomy-melatonine (PM) group underwent sympathectomy and pinealectomy. The C group was kept under a normal circadian rhythm for 10 days, and the other groups were kept under continuous exposure to light for the same period. The PM group received subcutaneously 10 mg.kg-1 of melatonine every day. Serum LH levels were measured 10 days following these experiments. With regard to serum LH levels, the differences among C group, L group, and S group were similar to those previously reported. It was higher in P group (2.53 +/- 0.40 ng.ml-1) than in S group (1.58 +/- 0.61 ng.ml-1), and lower in PM group (2.08 +/- 0.31 ng.ml-1) than in P group. In conclusion, it is suggested that the endocrine activity of melatonine from the pineal gland plays an important role in the appearance of the effect of cervical sympathectomy.     

Biphasic effects of ethanol on open-field activity: Sensitivity and tolerance in C57BL/6N and DBA/2N mice.

Male C57BL/6N (C57) and DBA/2N (DBA) inbred mice were found to differ in open-field behavior after an acute ip injection of ethanol and in the development of tolerance to repeated injections. DBA Ss showed only increased activity for 28 min after ethanol doses up to 2.67 g/kg when compared with saline-injected controls; C57 Ss showed dose-related increases in activity during the first 4 min, followed by dose-related decreases in activity. The effects endured for at least 60 min after injection in both strains. In a 3rd experiment, Ss were injected daily with saline or 2 g/kg ethanol and tested on Days 1, 5, 9, and 13 for open-field activity. On the 17th day, all Ss were tested after an ethanol injection; neither strain showed tolerance to the activity-stimulating effect of ethanol. Some evidence for tolerance to the effect of ethanol to reduce activity in C57's was found. In a 4th experiment, twice-daily injections of ethanol for 10 days produced marked tolerance to the depressant effect of an injection on the 11th day in C57 Ss; no tolerance to the stimulant effect of ethanol was found. DBA Ss injected twice daily for 19 days did not display tolerance when tested on Days 10 or 20, instead showing more marked stimulation of activity after ethanol than mice treated chronically with saline. Implications for the genetic control of responses to ethanol are discussed. (21 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

A comparison of the abilities of chlorpromazine and molindone to interact adversely with guanethidine

Chlorpromazine and molindone were tested for their abilities to impair conditioned avoidance behavior of rats. Chlorpromazine was effective within the dose range of 0.3 to 7.0 mg/kg (ID50approximately 2.0 mg/kg); molindone was effective within the range of 0.3 to 5.0 mg/kg (ID50 approximately 0.6 mg/kg). Behaviorally relevant doses of chlorpromazine and molindone were then tested for their effects on blood pressure and on adrenergic mechanisms. When given intravenously to anesthetized, hypertensive animals, both drugs (1.0 mg/kg) produced significant but transient vasodepression. When given intraperitoneally to anesthetized or to conscious hypertensive rats, the drugs did not produce significant effects on blood pressure. Both drugs (1.0 mg/kg) blocked responses to an alpha agonist (methoxamine), but chlorpromazine was significantly more potent than molindone. In addition, chlorpromazine produced a dose-dependent (1.0-10.0 mg/kg) inhibition of 3H-l-norepinephrine uptake into heart, but molindone at the same doses produced no inhibition of uptake. In related experiments, it was found that guanethidine (50 mg/kg) was an effective agent for lowering blood pressure of hypertensive rats. When chlorpromazine (3-10 mg/kg) was administered concomitantly with guanethidine, the blood pressure lowering properties of guanethidine were diminished or abolished. When molindone (1-10 mg/kg) was administered concomitantly with guanethidine, there was no loss of blood pressure control. It is concluded that molindone is an important drug, because it is an antipsychotic agent that does not interact adversely with guanethidine.     

Influence of high titers of maternal antibody on the serologic response of infants to diphtheria vaccination at three, five and twelve months of age

Diphtheria antitoxin was determined in serum from 44 pregnant women, of whom 26 had received one injection of diphtheria toxoid during pregnancy. Their infants were vaccinated with a combined diphtheria-tetanus vaccine at 3, 5 and 12 months of age. This vaccination schedule has been used in Sweden since 1986, replacing the old schedule of vaccination at 3, 4.5 and 6 months of age originally designed for diphtheria-tetanus-pertussis vaccine, which had not been used after cessation of general vaccination against pertussis in 1979. Serum samples from the infants were obtained at 3, 7 and 18 months of age. After 2 injections infants of mothers with high antitoxin titers, > or = 0.1 IU/ml, tended to have lower antitoxin titers than infants of mothers with low antitoxin concentrations (P = 0.067). All children had, however, antitoxin above the minimum protective level of 0.01 IU/ml. Median antitoxin titers were 1.6 IU/ml in both groups after the third booster injection. Four infants of mothers who had been vaccinated during pregnancy and who had titers of > or = 0.4 IU/ml did not reach the 0.1 IU/ml level after 2 injections: all 4 responded with high antitoxin titers after the third dose. Thus all infants were primed by 2 doses of vaccine, irrespective of maternal antibody concentration. The repressive effect of maternal antibody on titers noted after 2 doses was no longer observed after the third, booster dose.     

Temporal factors influence recovery of function after embryonic brain tissue transplants in adult rats with frontal cortex lesions.

Adult rats with lesions of the medial frontal cortex received implants of frontal cortex taken from embryos on the 19th day of gestation and placed directly into the zone of injury at 7, 14, 30, or 60 days after initial surgery. Another group was given bilateral frontal lesions, followed 20 days later by a second small lesion to enhance the release of putative neurotrophic factors. They then received transplants 7 days after this second operation. All rats began postoperative training on a spatial alternation learning task within 4 days after the implants of fetal tissue. The brain-damaged rats with transplants at 7 or 14 days after surgery significantly improved postoperative acquisition of spatial alternation. Transplants made 30 or 60 days postoperatively had no effect; these groups were as impaired as those with lesions alone. The animals given a second, "priming" lesion after a 20-day delay, followed by implants of fetal brain tissue, performed as poorly as the group with frontal cortex lesions alone. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Safety of single large oral doses of guanethidine

The cardiovascular effects of single 100-mg doses of guanethidine were assessed in hypertensive patients by measurement of arterial pressure, heart rate, and systolic time intervals. In the 3-hr period following a dose there was no evidence of an inotropic effect. Therefore, large doses of guanethidine as required for the guanethidine loading regimen would seem to be safe even in patients in whom inotropic effects of released catecholamines would be contraindicated.     

Effects of morphine, ethylketocyclazocine, and N-allylnormetazocine on classical conditioning of the rabbit nictitating membrane response.

The nictitating membrane response of 120 New Zealand albino rabbits was classically conditioned to tone and light conditioned stimuli (CSs) presented for 800 msec before delivery of a 100-msec unconditioned shock stimulus. Both the mu receptor agonist morphine (5 mg/kg) and the kappa receptor agonist ethylketocyclazocine (1 mg/kg) significantly retarded the acquisition of conditioned responses (CRs). The retardant effects of both morphine and ethylketocyclazocine on CR acquisition could still be detected when the Ss were tested 5 days after cessation of drug injections. The sigma receptor agonist N-allylnormetazocine (5 mg/kg) had no effect on acquisition. The retardant effects of morphine and ethylketocyclazocine on acquisition were significantly antagonized by both naloxone (1 mg/kg) and N-allylnormetazocine. It is suggested that mu and possibly kappa receptors are involved in the retardant effects of opiates on CR acquisition. (14 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)