13C NMR relaxation studies of poly(vinyl alcohol) and its derivatives

Spin-lattice relaxation times (T₁) have been measured by ¹³C NMR for poly(vinyl alcohol), poly(vinyl benzoate), poly(vinyl cinnamate) and poly(vinyl acetate) in dimethyl sulfoxide as a function of temperature and concentration. As expected, T₁ increases with increasing temperature and decreases with increasing polymer concentration. The influence of the microstructure (tacticity) of the polymers on the relaxation times is negligible. T₁ for the methine carbon of the polymer main chain is observed to serve as a measure of the rigidity and/or mobility of the chain. Assuming isotropic motion of the polymer chains, the activation energies for the protonated carbons were determined using the calculated correlation times.     

Ca2+–calmodulin-dependent protein kinase expression and signalling in skeletal muscle during exercise

Ca²⁺ signalling is proposed to play an important role in skeletal muscle function during exercise. Here, we examined the expression of multifunctional Ca²⁺–calmodulin-dependent protein kinases (CaMK) in human skeletal muscle and show that CaMKII and CaMKK, but not CaMKI or CaMKIV, are expressed. Furthermore, the effect of exercise duration and intensity on skeletal muscle CaMKII activity and phosphorylation of downstream targets was examined. Eight healthy men exercised at ∼67% of peak pulmonary O₂ uptake     with muscle samples taken at rest and after 1, 10, 30, 60 and 90 min of exercise. Ten other men exercised for three consecutive 10 min bouts at 35%, 60% and 85%     with muscle samples taken at rest, at the end of each interval and 30 min post-exercise. There was a rapid and transient increase in autonomous CaMKII activity and CaMKII phosphorylation at Thr²⁸⁷ in skeletal muscle during exercise. Furthermore, the phosphorylation of phospholamban (PLN) at Thr¹⁷, which was identified as a CaMKII substrate in skeletal muscle, was rapidly (< 1 min) increased by exercise, and remained phosphorylated 5-fold above basal level during 90 min of exercise. The phosphorylation of serum response factor at Ser¹⁰³, a putative CaMKII substrate, was higher after 30 min of exercise. PLN phosphorylation at Thr¹⁷ was higher with increasing exercise intensities. These data indicate that CaMKII is the major multifunctional CaMK in skeletal muscle and its activation occurs rapidly and is sustained during continuous exercise, with the activation being greater during intense exercise.     

[3H] UK-14,304, a new agonist ligand of α2-adrenoceptors: a comparative study with human and rat tissue

Summary [³H] UK-14,304 was used to investigate ₂-adrenoceptors in rat brain and human platelets. Receptor pharmacology revealed that the ligand binds with high affinity to ₂-adrenoceptors. Psychoactive substances like neuroleptics, antidepressants, and-carbolines displace [³H] UK-14,304 from its binding sites in the lower micromolar range. A Hill number around 2 for most neuroleptics suggests a positive cooperativity with the ₂-adrenoceptors.Comparative studies with [³H] UK-14,304 and [³H] clonidine utilizing platelet membranes from human volunteers demonstrated that the former ligand is more suitable to investigate possible changes of ₂-adrenoceptors; [³H] UK-14,304 labels more receptors with a lower standard deviation, whereby the volume of the blood sample amounted to 35 ml instead of 50 ml required for [³H] clonidine as ligand. No sex differences of binding constants were detected, however an inverse correlation of maximum number of binding sites and affinity was found for female subjects with both ligands.No age-dependent changes of B_max and K_D-values were observed in the range of 24 to 59 years.     

History of neuromorphometry

The history of morphometry begins in the middle of the last century. At the turn of the century impulses had decreased. The alterations arising during the preparation of the tissues were almost unknown. For example, the dogma of the loss of neurons during aging was conditioned by age-dependent histological shringage of the brain. Beginning in the thirties of this century new thoughts have given impulses to new morphometric investigation. In the neurosciences important impulses came from Bok. In 1961 Elias introduced the term "stereology" as a new interdisciplinary science in order to communicate the different developments. Since 1970 the computer and image analysis have brought a new dimension to morphometric research. This paper describes some neuromorphometrical developments. An increasing accuracy of results regarding density and amount of neurons can be estimated with facilitated counting procedures. A similar development can be observed for the estimation of neuronal sizes and their size distribution as well as for the volume-parts of the average perikaryon volume fraction (grey cell coefficient). The morphometry of dendritic tree and the ultrastructure of neuropil are briefly mentioned.     

Phase I/II tolerability/pharmacokinetic study with one-hour intravenous infusion of doxifluiridine (5′-dFUrd) 3 g/m2 VS 5 g/m2 QD x 5 per month

Summary Eighteen patients with advanced solid cancer were treated with daily 5-dFUrd infusions given over 1 h on days 1–5 of a 4-week cycle. Nine patients received 3 g/m² 5-dFUrd daily and another nine patients 5 g/m². One patient on 5 g/m² 5-dFUrd was not fully evaluable for tolerability due to early death (progressive disease) 4 weeks after the first cycle. A total of 48 cycles was given. The gastrointestinal and hematological toxicity was generally mild (grade 1–2). Central neurotoxicity (ataxia, unsteadiness, diplopia, dysarthria, sometimes confusion) was observed in 7 of 8 patients on 5 g/m² 5-dFUrd leading to premature discontinuation of treatment in 3 patients (after 2 cycles). Only 3 of the 9 patients in the 3 g/m² group had slight signs of cerebellopathy. Typically, the reversible neurological side effects started at the end of the 2nd week of a cycle. The serum elimination kinetics of 5-dEUrd and its metabolites 5-FU and 5-dFUH₂ have been investigated in the serum and showed very low intra- and interindividual variations. Peak concentrations of the 5-dFUrd at the end of the infusion approximated 500 mol/l and 1000 mol/l for the 3 g/m² and 5 g/m² group, respectively. The peak of the serum 5-FU was reached at the same time, the ratio 5-FU/5-dFUrd being around 10%. The elimination half-life time for 5-FU was protracted by a factor of 2–3 compared with the direct injection of 5-FU.Monthly infusion of 5-dFUrd 5 mg/m² per day on days 1–5 lead to an unacceptable frequency and degree of neurological toxicity. Similar infusions of 5-dFUrd 3 g/m² per day on days 1–5 were well tolerated.     

Rupture of splanchnic artery aneurysms

The results of surgical therapy for acute ruptured splanchnic artery aneurysms in 6 patients treated at Helsinki University Central Hospital from 1964 to 1984 were analyzed. There were 3 patients with ruptured splenic, 2 with ruptured hepatic and 1 with ruptured superior mesenteric artery aneurysms. The condition remained undiagnosed in all patients preoperatively, and the diagnosis was obtained only at emergency laparotomy performed for severe shock, abdominal pain, and distension. Five of the 6 patients survived, including a pregnant woman, who gave birth to a living baby by ceserean section. The results indicate that immediate, aggressive surgical approach dictated by the clinical condition of the patient affords good survival in patients suffering from acute rupture of splanchnic artery aneurysms.

---

Resumen Se analizan los resultados del tratamiento quirúrgico de la ruptura aguda de aneurismas de arterias esplnicas en 6 pacientes manejados en el Hospital Central de la Universidad de Helsinki en el periodo 1964–1984. Se presentaron 3 pacientes con ruptura de aneurismas de la arteria esplénica, 2 de la hepática y 1 de la mesentérica superior. La condición clínica se mantuvo sin diagnóstico durante la fase preoperatoria, y el diagnóstico sólo fue hecho en el curso de la laparotomía, procedimiento que fue realizado por shock severo, dolor abdominal y distensión. Cinco de los 6 pacientes sobrevivieron, incluyendo una mujer embarazada, quien dio a luz un niño vivo mediante sección cesárea. Los resultados indican que el enfoque quirúrgico inicial agresivo indicado por la condición clínica del paciente ofrece una buena oportunidad de supervivencia en pacientes que presentan ruptura de aneurismas de las arterias esplácnicas.

---

Résumé Les résultats du traitement chirurgical de 6 ruptures d'anévrysmes des artères splanchniques traités à l'Hôpital Central Universitaire d'Helsinki de 1964 à 1984 sont étudiés par les auteurs. Ils concernent la rupture anévrysmale de 3 artères spléniques, de 2 artères hépatiques, de 1 artère mésentérique. Le diagnostic ne fut porté qu'au moment de l'intervention d'urgence pratiquée en présence d'un état de choc sévère s'accompagnant de douleur et de distension abdominales. Cinq des 6 opérés ont survécu, dont une femme enceinte chez qui une césarienne fut pratiquée avec succès. Ces résultats plaident en faveur de l'action chirurgicale d'urgence.

     

Epidemiologische Ansätze zur Klärung wichtiger Forschungsfragen zu COVID-19 – eine Übersicht

Bundesgesundheitsblatt - Gesundheitsforschung - Gesundheitsschutz - Die Epidemiologie als wissenschaftliche Disziplin ist prädestiniert dafür, Kernfragen der COVID-19-Pandemie zu...     

Prevalence of Masturbation and Associated Factors Among Older Adults in Four European Countries

Solitary sexual activity is a free, safe, and accessible way to experience sexual pleasure. Despite these advantages, research on masturbation in later life is highly understudied. Using data from a cross-sectional probability-based survey of 3816 European adults (mean age 67 years; range 60–75 years), we explored several sociodemographic, health, attitudinal, and sexual behavioral factors associated with reported masturbation frequency. Across all countries, between 41% and 65% of men and 27% and 40% of women reported any masturbation in the preceding month. Satisfaction with sexual activity and attitudes related to disapproval of sex without love were significant predictors of reported masturbation in almost all countries and in both genders. Age, education, self-perceived health, and depression were for the most part predictive of men’s reported masturbation, but not women’s. Generally, those believing sex is beneficial to older people were more likely to masturbate, while less permissive attitudes decreased the likelihood of reporting masturbation. To improve healthy sexual aging, misinformation about masturbation and sexual attitudes in older people need to be addressed.

     

The midsagittal area of the corpus callosum and total neocortical volume differ in three inbred strains of mice

Differences in the midsagittal area of the corpus callosum have been reported between human males and females, between handled and nonhandled rats, and both within and between various strains of mice. This measure has, in addition, been related to handedness in humans and "pawedness" in certain strains of mice. The present study investigated the between- and within-strain differences in three inbred strains of mice, two with autoimmune disorders and spontaneously occurring developmental neuropathology, in the midsagittal area of the corpus callosum, the total neocortical volume, and the asymmetry of the neocortex. These morphometric measures were obtained from coronally sectioned celloidin-embedded material from New Zealand Black (NZB/BINJ), BXSB/MpJ, and DBA/2J mouse strains. NZB mice had a total neocortical volume larger than that of either the BXSB or DBA strains, whereas the BSXB mice had a midsagittal area of the corpus callosum larger than that of either of the other two strains. In addition, there was a positive correlation between these two measures. There was no correlation between total neocortical asymmetry and midsagittal area of the corpus callosum in any of the three strains. Finally, there were no differences in any morphometric measure between animals with or without developmental neuropathology in any given strain.     

Biotransformation of lovastatin--III. Effect of cimetidine and famotidine on in vitro metabolism of lovastatin by rat and human liver microsomes

The effects of the H2-receptor antagonists, cimetidine and famotidine, on the microsomal metabolism of [14C]lovastatin were investigated. Liver microsomes were prepared from control, phenobarbital- and 3-methylcholanthrene-pretreated rats and humans (male and female). Concentration-dependent inhibition of the metabolism of lovastatin (0.1 mM) was observed with cimetidine (0.1 to 1.0 mM). In contrast, famotidine at a similar concentration was a very weak inhibitor. The formation of 6'beta-hydroxy-lovastatin, the major microsomal metabolite of lovastatin, was similarly inhibited. The results suggest that in vivo metabolic interaction with concomitantly administered lovastatin is less likely with famotidine than with cimetidine. Phenobarbital pretreatment produced 58% stimulation in overall metabolism, whereas 3-methylcholanthrene pretreatment had no effect relative to control rats (5.4 nmol/mg protein/min). Liver microsomes from phenobarbital-pretreated rats produced 67% more of the 6'beta-hydroxy-lovastatin but 63-66% less of the 3'-hydroxy and 6'-exomethylene metabolites. Liver microsomes from 3-methylcholanthrene-treated rats also produced less 3"-hydroxy-lovastatin (49%) but similar quantities of the other two metabolites. 6'beta-Hydroxy-lovastatin was a major metabolite with human liver microsomes. Interestingly with these microsomes, hydroxylation at the 3'-position of the molecule was a negligible pathway and hydrolysis to the hydroxy acid form was not observed. The formation of 6'-exomethylene-lovastatin was also catalyzed by human liver microsomes (0.5 to 0.8 nmol/mg protein/min).