Supersensitivity to isoprenaline induced in rats by prolonged isolation

1 The effect of isoprenaline on diastolic blood pressure and heart rate was determined in anaesthetized male rats which had been housed individually for 6-8 weeks after weaning, and compared with its effect in group-housed litter-mate controls.2 Isoprenaline caused a significantly greater fall in diastolic pressure in isolated rats and a greater increase in heart rate.3 Low doses of noradrenaline (5-10 ng) caused vasodepressor responses in isolated, but not in group-housed rats.4 The pressor response to noradrenaline, which was smaller in isolated rats, was increased to the level of group-housed controls by (+/-)-propranolol.5 Prolonged isolation of rats may bring about an increase in sensitivity of beta-adrenoceptors to isoprenaline and noradrenaline.     

Differential long-term effect of AF64A on [H]ACh synthesis and release in rat hippocampal synaptosomes

The activities of various presynaptic cholinergic parameters were determined in hippocampal synaptosomes of rats 29 weeks after intracerebroventricular injection of ethylcholine aziridinium (AF64A) (3 nmol/2 μl/side) or vehicle (saline). Synaptosomes were preloaded with [³H]choline ([³H]Ch), treated with diisopropyl fluorophosphate to inhibit cholinesterase activity and then were assayed for their content of [³H]Ch and [³H]acetylcholine ([³H]ACh) and for their ability to synthesize and release [³H]ACh. In synaptosomes from AF64A-treated rats compared with synaptosomes from vehicle-treated rats we observed that: (i) specific uptake of [³H]ACh was reduced to 60% of control; (ii) residing [³H]ACh levels were 43% of control while residing [³H]Ch levels were 72% of control; (iii) basal and K⁺-induced [³H]ACh release were 77% and 73% of control, respectively; (iv) high K⁺-induced synthesis of [³H]ACh was only 9% of control; (v) but, choline acetyltransferase activity remained relatively high, being 80% of control. These results suggest that AF64A-induced cholinergic hypofunction is expressed by both loss of some cholinergic neurons and impairment in the functioning of the spared neurons.     

Severe hypophosphatemia in sepsis as a mortality predictor

Hypophosphatemia has long been reported to be associated with sepsis and has been correlated with sepsis severity. This retrospective study was undertaken at a university hospital to determine whether severe hypophosphatemia could serve as a mortality predictor in septic patients. Charts of 6,190 septic patients who were hospitalized during one year (2001-02) were examined. Fifty-five patients were selected and were divided into 2 groups: group 1 comprised 26 patients with severe hypophosphatemia (serum inorganic phosphate (Pi) <1 mg/dl); group 2 comprised 29 patients without severe hypophosphatemia (Pi >1 mg/dl. The patients' charts were reviewed and information was collected regarding medical anamnesis, physical examination, hematological and biochemical analyses, chest x-ray, and cultures of blood and urine. The results demonstrated that 80.8% of the patients with severe hypophosphatemia died, vs 34.5% of the patients without severe hypophosphatemia (p = 0.001). Being in the severe hypophosphatemic group increased the risk of death by nearly 8-fold (odds ratio = 7.98; 95% CI = 2.3 to 27.6). These findings indicate that severe hypophosphatemia can serve as an independent mortality predictor in sepsis.     

Reducing blood transfusion requirements in preterm infants by a new device: a pilot study

Objective: To test a new device designed to salvage red blood cells (RBCs) from blood samples drawn from preterm infants, with the intent of decreasing blood loss and lowering the requirements for RBC transfusions.
Design: A case-controlled pilot study was conducted in two Israeli neonatal intensive care units in large municipal hospitals. Twenty low-birthweight preterm infants were randomly and equally divided into the ErythroSave™ group or a control group. All blood tests in the study group (except for complete blood count and coagulation parameters) were obtained during the first week of life by the new device in the study group and by ordinary syringes in the control group. The main outcome measure was the total number of units of blood needed.
Results: The average volume of blood obtained for laboratory analyses from each infant was 27 mL in the ErythroSave group and 24 mL in controls (not significant). The average volume of transfused packed cells was 6.4 mL for the ErythroSave group and 21.3 mL for the controls (p = 0.008).
Conclusion: The use of ErythroSave for sampling blood significantly reduced blood transfusion requirements in premature infants compared to sampling by conventional syringes.     

The AG1478 tyrosine kinase inhibitor is an effective suppressor of leiomyoma cell growth

BACKGROUND: Uterine leiomyomas are the most common benign smoothmuscle cell tumours in women. Formation of leiomyomas, stillnot completely understood, is viewed as a multistep process,with involvement of ovarian steroid hormones, cytokines andgrowth factors. Our study aimed to identify tyrosine kinaseinhibitors as potential ‘signal transduction therapeutics’for leiomyomas, underlying the effect of ovarian steroidal hormones.METHODS: The selective epidermal growth factor (EGF) receptorblocker AG1478 was evaluated as a potential target, since EGFhas been shown to mediate estrogen action and to play a crucialrole in regulating leiomyoma growth. Paired cultures of leiomyomaand normal myometrium samples were established and the suppressiveeffect of AG1478 on the cells prior and subsequent to steroidalhormone treatment was examined: cell proliferation, recoveryafter treatment, cell cycle analysis and immunochemical analysisof relevant proteins. RESULTS: Leiomyoma cell growth is effectivelyblocked by AG1478 and is unaffected by the presence of physiologicalconcentrations of progesterone and estradiol. AG1478 (10 µM)completely suppressed proliferation and the cells did not recoverafter cessation of treatment. CONCLUSION: The growth-arrestingproperties of AG1478, unaffected by ovarian steroidal hormones,identify it as a potential lead agent for the non-surgical managementof uterine leiomyomas.     

Prenatal diagnosis of Meckel syndrome: alpha-feto protein and beta-trace protein in amniotic fluid

Meckel syndrome was diagnosed prenatally by α-feto protein and β-trace protein determinations in amniotic fluid. No central nervous system anomalies were detected in the affected fetus, who presented with large polycystic kidneys and polydactyly. An excessive synthesis of these fetal proteins by the dysplastic kidneys is suggested, allowing for the possibility of prenatal diagnosis of polycystic kidneys in families at risk for this disease.
The present family emphasizes the importance of amniocentesis in pregnancies at risk for Meckel syndrome, regardless of the presence of a defect in neural tube closure.     

Satellite cells from dystrophic (mdx) mice display accelerated differentiation in primary cultures and in isolated myofibers.

In the dystrophic (mdx) mouse, skeletal muscle undergoes cycles of degeneration and regeneration, and myogenic progenitors (satellite cells) show ongoing proliferation and differentiation at a time when counterpart cells in normal healthy muscle enter quiescence. However, it remains unclear whether this enhanced satellite cell activity is triggered solely by the muscle environment or is also governed by factors inherent in satellite cells. To obtain a better picture of myogenesis in dystrophic muscle, a direct cell-by-cell analysis was performed to compare satellite cell dynamics from mdx and normal (C57Bl/10) mice in two cell culture models. In one model, the kinetics of satellite cell differentiation was quantified in primary cell cultures from diaphragm and limb muscles by immunodetection of MyoD, myogenin, and MEF2. In mdx cell cultures, myogenin protein was expressed earlier than normal and was followed more rapidly by dual myogenin/MEF2A expression and myotube formation. In the second model, the dynamics of satellite cell myogenesis were investigated in cultured myofibers isolated from flexor digitorum brevis (FDB) muscle, which retain satellite cells in the native position. Consistent with primary cultures, satellite cells in mdx myofibers displayed earlier myogenin expression, as well as an enhanced number of myogenin-expressing satellite cells per myofiber compared to normal. The addition of fibroblast growth factor 2 (FGF2) led to an increase in the number of satellite cells expressing myogenin in normal and mdx myofibers. However, the extent of the FGF effect was more robust in mdx myofibers. Notably, many myonuclei in mdx myofibers were centralized, evidence of segmental regeneration; all central nuclei and many peripheral nuclei in mdx myofibers were positive for MEF2A. Results indicated that myogenic cells in dystrophic muscle display accelerated differentiation. Furthermore, the study demonstrated that FDB myofibers are an excellent model of the in vivo state of muscle, as they accurately represented the dystrophic phenotype.