Suppression of blood monocyte and neutrophil chemotaxis in acute human malaria

Summary The host response to Plasmodia includes the production of enlarged populations of peripheral blood monocytes and tissue macrophages in the spleen and the liver. Since the hyperplasia of the mononuclear phagocyte system is believed to arise as a consequence of an enhanced blood monocyte influx, we tested monocyte chemotactic responsiveness in 19 patients with acute primary attack malaria. In addition, the neutrophil chemotaxis was measured in 12 patients. Before the initiation of antimalarial treatment a significant depression of monocyte chemotaxis was observed in approximately half of the patients when compared with healthy control subjects. The depression was found in Plasmodium falciparum malaria as well as in P. vivax or P. ovale malaria patients. The defective responsiveness was not receptor specific, since the responses towards casein and zymosan activated serum proved to be equally suppressed. The monocyte chemotaxis was followed in 14 of the patients, during treatment and after complete recovery. After 3 days of treatment the response had improved in most of the patients, and after 7 days all patients had a normal monocyte chemotaxis, which remained normal after one month. No significant differences between P. falciparum and P. vivax/ovale malaria was observed with respect to blood monocyte chemotactic responsiveness. Neutrophil chemotaxis in patients with P. falciparum infections was similarly suppressed before treatment (54% of controls), was still defective after 3 days of treatment, and nearly normalized after 7 days (87% of controls). Furthermore, monocyte phagocytic and candidacidal activities were assessed in the same patients on admission and during the follow-up. In contrast to chemotaxis, these functions were normal in all of the patients whenever measured. In conclusion, not all cell functions were altered in concert, and the previously unreported suppression of chemotactic migration might reflect a change in blood leucocyte subpopulations, deactivation in vivo or a direct suppressive effect of Plasmodia induced products.     

Mitral Annulus Calcification and Embolism

ABSTRACT. Of 388 patients consecutively referred to echocardiography, 49 were suspected of having a cardiac source of systemic arterial embolism (SE). Mitral annulus calcification (MAC) was revealed in 27% of the patients with SE and in 8% of the remaining patients (p<0.05). The group of patients with SE were slightly older (median age 67 years) and included more female patients (47%) compared to the group without SE (62 years, p<0.05; 40% female patients, p>0.05). However, the small differences in age and sex distribution did not explain satisfactorily the considerably increased prevalence of MAC in the group of patients with SE. Our preliminary data indicated that thromboembolism caused by left atrial dilatation and atrial fibrillation might be the most important cause of the condition in patients with MAC and SE. However, the significance of the possible mechanisms of embolism in patients with MAC and the incidence of the complication should be further clarified before therapy and prophylaxis can be suggested.     

Comparison of bone reactions to coated tricalcium phosphate and pure titanium dental implants in the canine iliac crest

Abstract — Titanium and TCP-coated implants were compared after insertion in the canine iliac crest. Observation time was 14 wk. Evaluation included pull-out tests, energy dispersive X-ray analysis, and histologic examination of in situ , undemineralized implants. The TCP-coated implants were more firmly attached to bone than were the titanium implants. The calcium/ phosphorus ratios around the titanium implants were higher than around the TCP-coated implants. Both types of implants were closely surrounded by bone after a 14-wk implantation.     

Comparison of the Action of Vitamin K1 with that of Synkavit in the Newborn

Summary
In newborn infants with varying degrees of prolonged prothrombin time no marked difference could be found between the velocity of action of vitamin K₁ (10 or 0.1 mg) or synkavit (10 or 0.1 mg) when administered intravenously. This was also the case when the two substances were given orally (10 mg). The result is in contrast to the known superiority of vitamin K₁ in vitamin K deficient chicks and in dicoumarol-treated chicks or patients. Intravenous injection of vitamin K₁ as well as of synkavit acts more slowly in infants than in chicks. Ingestion of d, l -α-tocopherol acetate (50 mg) to infants 24 hours before the injection of vitamin K₁ did not result in a more rapid action of the latter substance.     

Transport of glucose across the blood-brain barrier: Reevaluation of the accelerative exchange diffusion

In an earlier study of glucose transport across the blood-brain barrier it was concluded that the kinetic transport constants increase as the brain glucose concentration increases, a finding that was attributed to accelerative exchange diffusion (Betz et al. 1975). The conclusion, however, relied upon application of a commonly used simplified treatment of tracer extraction data. In this study it is demonstrated that the simplified treatment is applicable only in the case of zero brain glucose concentration, and a more general model for determination of the kinetic constants is developed. Re-analysis by this model of the data of Betz et al. (1975)—comprising a range of brain glucose concentrations—gave kinetic constants which did not vary significantly over a wide range of brain glucose concentrations. For brain glucose concentrations up to about 12 mmol l^-1, the kinetic constants obtained for glucose transport across the blood-brain barrier are Km =6.18±0.38mmol l^-1 V_max= 1.65±0.06 μmol g-¹ min^-1     

Effect of vein pump activation upon muscle blood flow and venous pressure in the human leg

The effect of vein pump activation upon superficial venous pressure and blood flow in human skeletal muscle tissue was studied in 7 healthy subjects. Blood flow was measured in the anterior tibia muscle by the local ¹³³Xe washout technique. The subjects were placed on a steeply tilted couch in nearly erect position. The vein pump in gastroenemius-soleus muscles was activated by heel-raisings. and the anterior tibial muscle remained relaxed during this procedure. Blood flow in the resting anterior tibial muscle was constant before, during and after 20 heel-raisings per min. A more heavy exercise with 40 heel-raisings per min increased blood flow about 100%. This increase in blood flow was absent during venous stasis (40 mmHg), and in areas infiltrated with lidocaine. It is concluded, that intense dynamic exercise in gastrocnemius-soleus muscles, in erect humans, increased blood flow considerably in another crural muscle remaining in the resting state. The present study strongly suggests, that the observed increase in blood flow, was associated with a decrease in regional subfascial venous pressure to below the threshold level of the local sympathetic veno-arteriolar reflex.     

DEVELOPMENTAL REGULATION OF TISSUE TRANSGLUTAMINASE DURING HUMAN PLACENTATION AND EXPRESSION IN NEOPLASTIC TROPHOBLAST

The expression of tissue transglutaminase (tTG) was studied during the formation of the normal human placenta and in molar pregnancies and choriocarcinoma, in order to correlate its expression with the functional characteristics of the recognized trophoblast cell types. tTG expression was found to be developmentally regulated. Before 6–7 weeks' gestation, only the chorionic villous cytotrophoblast expresses tTG. Thereafter the overlying syncytiotrophoblast becomes positive. tTG expression is gradually downregulated in the intermediate trophoblast cells emerging from the tips of the chorionic villi invading the uterine tissue. In the decidual wall, the intermediate trophoblast does not express tTG, whereas scattered syncytial cells, the placental bed giant cells, express tTG. Villi from complete hydatidiform mole (CHM) show tTG expression in both the cyto- and the syncytiotrophoblast. The intermediate trophoblast cells from CHM show heterogeneous tTG expression, with a majority of negative cells, whereas extravillous syncytia always express tTG. In choriocarcinoma, the tumour cells show heterogeneous tTG expression, with a majority of positive cells. Analysis of tTG protein and mRNA in placental extracts by Western and Northern blotting did not provide evidence for expression of the truncated form of tTG found in some cell types. The regulated expression of tTG in the normal placenta suggests that the enzyme is involved in important trophoblastic functions and may participate in the control of invasion. © 1997 by John Wiley & Sons, Ltd.     

Effects of hypothyroidism and cholesterol feeding on the clearance of chylomicron remnants in vivo and by rat hepatocyte monolayers

Abstract. The hepatic catabolism of chylomicron remnants in normal rats and in hypothyroid rats which were either normocholesterolaemic or made hypercholesterolaemic by feeding cholesterol and cholic acid was studied in vivo and in hepatocyte monolayers.
In vivo , the clearance of injected chylomicron remnants labelled with either cholesteryl- or retinyl ester was delayed in the hypercholesterolaemic hypothyroid rats, but not in normocholesterolaemic hypothyroid rats.
Cholesteryl-ester-rich hepatocytes from hypercholesterolaemic hypothyroid rats took up remnants less efficiently than did normal hepatocytes. Hepatocytes from normocholesterolaemic hypothyroid rats had a lower cholesteryl ester content and took up remant particles to a greater degree than did normal hepatocytes. When normal hepatocytes were incubated with hypercholesterolaemic serum or with mevalonolactone, which increased cell cholesteryl ester content, there was a slight suppression of remnant uptake. Also, addition of triiodothyronine to hepatocyte monolayers suppressed rather than increased uptake of chylomicron remants in hepatocytes.
Thus, the study suggests that chylomicron remnant uptake by the liver is not inhibited by hypothyroidism per se but by the cholesterol accumulation in hepatocytes that is the consequence of cholesterol and bile acid feeding of the rats. Although the cholesteryl ester content in hepatocytes seems to determine remnant uptake, the regulation of uptake does not seem to be as effective as that of the LDL receptor in extrahepatic cells.     

Novel experimental Pseudomonas aeruginosa lung infection model mimicking long‐term host–pathogen interactions in cystic fibrosis

The dominant cause of premature death in patients suffering from cystic fibrosis (CF) is chronic lung infection with Pseudomonas aeruginosa. The chronic lung infection often lasts for decades with just one clone. However, as a result of inflammation, antibiotic treatment and different niches in the lungs, the clone undergoes significant genetic changes, resulting in diversifying geno‐ and phenotypes. Such an adaptation may generate different host responses. To experimentally reflect the year‐long chronic lung infection in CF, groups of BALB/c mice were infected with clonal isolates from different periods (1980, 1988, 1997, 1999 and 2003) of the chronic lung infection of one CF patient using the seaweed alginate embedment model. The results showed that the non‐mucoid clones reduced their virulence over time, resulting in faster clearing of the bacteria from the lungs, improved pathology and reduced pulmonary production of macrophage inflammatory protein‐2 (MIP‐2) and granulocyte colony‐stimulating factor (G‐CSF). In contrast, the mucoid clones were more virulent and virulence increased with time, resulting in impaired pulmonary clearing of the latest clone, severe inflammation and increased pulmonary MIP‐2 and G‐CSF production. In conclusion, adaptation of P. aeruginosa in CF is reflected by changed ability to establish lung infection and results in distinct host responses to mucoid and non‐mucoid phenotypes.     

Regional variations in skin perfusion and skin thickness may contribute to varying efficacy of topical, local anaesthetics in neonates

The national Swedish screening programme for inborn errors of metabolism includes blood sampling from all neonates. Heel lancing has hitherto been the method of choice for these screening tests. Studies have recently been done to find out whether the use of EMLA can alleviate pain caused by heel lancing. EMLA had little, if any (1, 2) effect when applied to the heel of full term babies. Similar results were reported concerning preterm infants (3, 4). Other authors have found that differences in skin thickness or in skin blood perfusion may influence the effect of EMLA (5, 6). The aim of this study was to establish whether differences in skin thickness or in skin blood perfusion were present in three regions: the forehead, the dorsum of the hand and the heel. Ten healthy full term neonates were included in the study on skin perfusion. Measurements were made with a laser Doppler flux meter. Twenty-seven healthy full term neonates were included for measurements of skin thickness using a high frequency B-mode ultrasonic meter. The heel skin perfusion was two to three times higher than the skin perfusion at the dorsum of the hand and at the forehead but there was no significant difference when comparing skin thickness of the heel with the dorsum of the hand and the forehead. A rapid clearance of a topically applied local anaesthetic, due to high cutaneous blood flow, may explain why EMLA seems to be of little value when it is applied to the neonatal heel.