Pharmacological properties of Ca2+-activated K+ currents of ramified murine brain macrophages

Using the whole-cell configuration of the patch clamp technique, calcium-activated potassium currents (I_K,Ca) were investigated in ramified murine brain macrophages. In order to induce I_K,Ca the intracellular concentration of nominal free Ca²⁺ was adjusted to 1μM. The Ca²⁺-activated K⁺ current of brain macrophages did not show any voltage dependence at test potentials between –120 and +30mV. A tenfold change in extracellular K⁺ concentration shifted the reversal potential of I_K,Ca by 51mV. The bee venom toxin apamin applied at concentrations of up to 1μM did not affect I_K,Ca. Ca²⁺-activated K⁺ currents of ramified brain macrophages were highly sensitive to extracellularly applied charybdotoxin (CTX). The half-maximal effective concentration of CTX was calculated to be 4.3nM. In contrast to CTX, the scorpion toxin kaliotoxin did not inhibit I_K,Ca at concentrations between 1 and 50nM. Tetraethylammonium (TEA) blocked 8.0% of I_K,Ca at a concentration of 1mM, whereas 31.4% of current was blocked by 10mM TEA. Several inorganic polyvalent cations were tested at a concentration of 2mM for their ability to block I_K,Ca. La³⁺ reduced I_K,Ca by 72.8%, whereas Cd²⁺ decreased I_K,Ca by 17.4%; in contrast, Ni²⁺ did not have any effect on I_K,Ca. Ba²⁺ applied at a concentration of 1mM reduced I_K,Ca voltage-dependently at hyperpolarizing potentials. Received: 17 January / Accepted: 5 May 1997     

HEAD INJURY IN SOUTH AUSTRALIA: INCIDENCE OF HOSPITAL ATTENDANCE AND DISABILITY BASED ON A ONE-YEAR SAMPLE

A full-year sample of 1,698 head injuries treated at the accident and emergency department of a major metropolitan public hospital during 1984 was traced. Using a combination of medical record review of all cases, questionnaires and personal clinical assessment, estimates were made of the incidence rates of hospital attendance, admission and disability due to head injury by residents in the region of the hospital as well as estimates of the extent of the head injury problem in South Australia. The estimates are known to underestimate the actual rates, but provide valuable information on the size of the significant public health problem of head injury morbidity, and the burden on community rehabilitation and support services.     

Evaluation of the Coulter Counter model S-Plus IV

Evaluation of linearity, carry-over, precision, and accuracy of a Coulter Counter model S-Plus IV prototype showed that they meet the manufacturer's specifications. The instrument also was compared with an earlier model. Correlations of the lymphocyte and granulocyte values in the three-part differential count with manual eye-count and a Technicon Hemalog D90 results were very close to the correlation of eye-count to Hemalog D90 results. The percentage of mononuclear cells showed acceptable correlation to the manual eye-count when monocytes were combined with blasts, eosinophils, and basophils. The medical effectiveness of the three-part differential was determined by comparison with manual eye-counts in 1,084 samples. The false positive and false negative values were 7.38% and 7.84%, respectively. The instrument has acceptable limits of operation. When combined with analysis of histograms by trained personnel, the three-part differential count is capable of screening for abnormalities that require further analysis.     

Heterosynaptic postactivation potentiation in hippocampal CA 3 neurons: Long-term changes of the postsynaptic potentials

Summary CA 3 neurons were excited synaptically by stimulation in the dentate hilus and the stratum radiatum of CA 1 in guinea pig hippocampal slices. Following repetitive stimulation (10–20 c/s, 10 s) of either stimulation site, the amplitudes of orthodromic population spikes or the probability of unitary discharges increased. Changes of the intracellularly recorded potentials were either (a) increased EPSP amplitudes associated with decreased IPSP amplitudes, or (b) increased IPSP amplitudes. A cell showing enhanced IPSPs after repetitive activation could respond with increased EPSP amplitudes and decreased IPSP amplitudes upon further repetitive activation. The potentiation, which was always preceded by a 5–10 min depression, lasted up to 3 h. This potentiation was heterosynaptic, since the responses to the non-stimulated input also changed and since the inputs were found to excite the pyramidal cells through separate synapses in double shock experiments. The heterosynaptic mode of the potentiation as well as the changes of the IPSPs indicate that not only the excitatory pathway but also the inhibitory pathway must be considered in explaining postactivation potentiation in this hippocampal field.     

Development of a new biodegradable intravascular polymer stent with simultaneous incorporation of bioactive substances

OBJECTIVE: Due to the thrombogenicity and permanent implant nature of metallic stents, bioresorable synthetic polymers have been proposed for stents and local drug delivery systems. Bioresorbable polyesters like poly(D,L-lactide) demonstrated excellent biocompatibility in various tissues. This paper describes a novel method for the molding of these polymers. The specific CESP-process (Controlled Expansion of Saturated Polymers) is characterised by the use of the plasticizer carbon dioxide and allows the incorporation of bioactive substances at physiologic temperatures into the polymer bulk and the production of complex designed implants. METHODS: The CESP-process is characterised by the exposure of an amorphous polymer to an inert gas at high pressure with a significant lower glass transition point. The plasticizing effect makes it possible to process polylactides at a temperature close to room temperature. The low process temperature constitutes a key advantage for thermally sensitive polymers and allows the incorporation of thermally sensitive pharmaceutical additives. To obtain some preliminary information on the biocompatibility, in vitro cell toxicity testing as well as drug release assessment was performed. RESULTS: Different polymer sheets were produced using the CESP-process. Cytotoxicity was not observed in any molded polymer material. According to the mechanical and biocompatibility results Poly(D,L-lactide) (P-DL-LA) was investigated in the CESP-process. Finite element analysis was used to test the possible geometry of an adequate stent. A helical design was chosen and a stent-prototype was produced using the CESP-process. Peroxidase activity as an incorporated marker enzyme could be measured over 6 weeks. Different drug release profiles were obtained due to various pore sizes of the polymer. CONCLUSIONS: The new CESP-process can be used to process biodegradable polymers and to mold different stent geometries without inducing cytotoxic effects to the material. Furthermore, this procedure permits the simultaneous incorporation of bioactive substances during the molding process. Drug release kinetics can be regulated by different pore sizes of the material.     

Using data from studies of health-related quality of life to describe clinical issues Examples from a longitudinal study of patients with advanced stages of cervical cancer

The focus of the paper is to describe how to present data from studies on health-related quality of life (H-QoL) in a way that is simple and clinically relevant. Data from a longitudinal study of patients with advanced stages of cervix cancer are used. One hundred and eighteen patients filled out questionnaires (including EORTC QLQ-C30) 7 times over a period of 2 years. The following issues are considered: (1) The use of a panel for an initial overview of data. (2) The visual difference between using mean and median values. (3) Box-whisker plots to illustrate the variability of the data. (4) The effect of combining categorical data into fewer categories. (5) Individual patient profiles showing the wide variability among patients. (6) A table showing the change of scores over a one-year period. (7) “Prognostic plots” dividing the initial scores and the following scores. (8) Plotting changes over time. (9) Illustration of the impact of non-random drop-out. (10) The effect of drop-out for the patients who fill out two sequential assessments. (11) The use of healthy controls to help answer the question “what is normal?”.     

Changes in Alcohol Consumption,Eating Behaviors,and Body Weight during Quarantine Measures: Analysis of the CoCo-Fakt Study

IntroductionPublic health measures enacted to reduce COVID-19 transmission have affected individuals'' lifestyles, mental health, and psychological well-being. To date, little is known how stay-at-home orders have influenced the eating behaviors, weight development, and alcohol consumption of quarantined persons. The CoCo-Fakt cohort study analyzed these parameters and their association with psychological distress and coping strategies.MethodsAn online survey was conducted of all persons who tested positive for SARS-CoV-2 (infected persons [IP]) between December 12, 2020, and January 6, 2021, as well as their close contacts (contact persons [CP]) registered by the public health department of Cologne. 8,075 of 33,699 individuals were included in the analysis. In addition to demographic data, psychological distress, and coping strategies, information on changes in body weight, eating, and drinking behaviors was collected.ResultsIP lost 1.2 ± 4.4 kg during the quarantine period, and CP gained 1.6 ± 4.1 kg. The reasons given by IP for weight change were mainly loss of taste and feeling sick, whereas CP were more likely than IP to eat out of boredom. Higher psychological burden and lower coping strategies were associated with both weight gain and loss. Of the 30.8% of participants who changed their alcohol consumption during the quarantine period, CP in particular drank more alcohol (IP 15.2%; CP 47.7%). Significantly less alcohol was consumed by individuals with higher coping scores.ConclusionIn this short but psychologically stressful period of stay-at-home orders, changes in eating and drinking behavior as well as weight development are evident, mainly in high-risk contacts. To avoid possible long-term sequelae, health authorities should take these findings into account during the quarantine period; in particular, general practitioners should consider these findings during follow-up.     

Neurocognitive outcome in patients with hypertyrosinemia type I after long-term treatment with NTBC

Objective  

The implementation of NTBC into treatment of hypertyrosinemia type I (HT I) greatly improved survival by prevention of acute liver failure and hepatocellular carcinoma. However, there are first reports of cognitive impairment in patients with elevated plasma tyrosine concentrations.