Chloroquine blood concentrations and malaria prophylaxis in Tanzanian women during the second and third trimesters of pregnancy

Objective: Routine malaria prophylaxis with chloroquine (CQ) is recommended to pregnant semi-immune women in several countries in Africa. The dosage is empirically based. We investigated whether blood CQ concentrations and apparent oral blood clearance (CL/F) change during the course of pregnancy. We also studied whether malaria parasites could be detected together with low CQ blood levels. Methods: Forty nine semi-immune Tanzanian women were recruited in the 16th week of pregnancy. They were given 310 mg oral CQ base once per week as prophylaxis during the whole pregnancy. Capillary blood samples were taken for analysis of CQ before treatment and at weeks 26 and 36. Blood samples were dried on filter paper and analysed by HPLC. Blood was also drawn to detect occurrence of malaria parasites. Results: A total of 25 women fulfilled the sampling schedule. CL/F increased significantly from 160 ml ·  min⁻¹ at week 26 to 180 ml · min⁻¹ at week 36. In 7 of 25 women, CL/F increased >20%. Trough blood CQ concentrations, determined on four occasions at week 26 and at week 36 varied between 200 and 900 nmol · l⁻¹. No statistically significant differences between occasions were seen. Malaria parasites were seen in two individuals early in pregnancy. Conclusion: Blood CQ CL/F showed a small increase during the course of pregnancy. The estimated mean blood CL/F values of 160 and 180 ml · min⁻¹ (week 26 and 36, respectively) were higher than the mean CL/F of 125 ml · min⁻¹ in non-pregnant individuals, published previously. Efficacy of higher dosages of CQ in malaria prophylaxis in pregnant women could, therefore, be evaluated in controlled trials in high-risk malaria areas. Received: 3 July 1996 / Accepted in revised form: 5 November 1996     

Mast cell activation markers for in vitro study

ABSTRACT

Mast cells (MCs) are well known for their role in allergic conditions. This cell can be activated by various types of secretagogues, ranging from a small chemical to a huge protein. Mast cell activation by secretagogues triggers the increase in intracellular calcium (iCa²⁺) concentration, granule trafficking, and exocytosis. Activated mast cells release their intra-granular pre-stored mediator or the newly synthesized mediator in the exocytosis process, in the form of degranulation or secretion. There are at least three types of exocytosis in mast cells, which are suggested to contribute to the release of different mediators, i.e.,, piecemeal, kiss-and-run, and compound exocytosis. The status of mast cells, i.e., activated or resting, is often determined by measuring the concentration of the released mediator such as histamine or β-hexosaminidase. This review summarizes several mast cell components that have been and are generally used as mast cell activation indicator, from the classical histamine and β-hexosaminidase measurement, to eicosanoid and granule trafficking observation. Basic principle of the component determination is also explained with their specified research application and purpose. The information will help to predict the experiment results with a certain study design.     

Identification and characterization of the scl gene encoding a group A Streptococcus extracellular protein virulence factor with similarity to human collagen

Group A Streptococcus (GAS) expresses cell surface proteins that mediate important biological functions such as resistance to phagocytosis, adherence to plasma and extracellular matrix proteins, and degradation of host proteins. An open reading frame encoding a protein of 348 amino acid residues was identified by analysis of the genome sequence available for a serotype M1 strain. The protein has an LPATGE sequence located near the carboxy terminus that matches the consensus sequence (LPXTGX) present in many gram-positive cell wall-anchored molecules. Importantly, the central region of this protein contains 50 contiguous Gly-X-X triplet amino acid motifs characteristic of the structure of human collagen. The structural gene (designated scl for streptococcal collagen-like) was present in all 50 GAS isolates tested, which together express 21 different M protein types and represent the breadth of genomic diversity in the species. DNA sequence analysis of the gene in these 50 isolates found that the number of contiguous Gly-X-X motifs ranged from 14 in serotype M6 isolates to 62 in a serotype M41 organism. M1 and M18 organisms had the identical allele, which indicates very recent horizontal gene transfer. The gene was transcribed abundantly in the logarithmic but not stationary phase of growth, a result consistent with the occurrence of a DNA sequence with substantial homology with a consensus Mga binding site immediately upstream of the scl open reading frame. Two isogenic mutant M1 strains created by nonpolar mutagenesis of the scl structural gene were not attenuated for mouse virulence as assessed by intraperitoneal inoculation. In contrast, the isogenic mutant derivative made from the M1 strain representative of the subclone most frequently causing human infections was significantly less virulent when inoculated subcutaneously into mice. In addition, both isogenic mutant strains had significantly reduced adherence to human A549 epithelial cells grown in culture. These studies identify a new extracellular GAS virulence factor that is widely distributed in the species and participates in adherence to host cells and soft tissue pathology.     

Combined effect of Controlling Nutritional Status and Acute Kidney Injury on severe COVID-19 short-term outcomes

Introduction/ObjectivesAcute kidney injury (AKI) and malnutrition are two complications commonly reported in severe forms of COVID-19, their combined effect on short-term mortality is, however, not yet investigated. The objective of this study is to determine both their individual and combined effects on short-term prognosis.Materials and methodsThis is a prospective, uni-centric study, including 247 severe COVID-19 patients, admitted between April 25th and June 20th, 2020, at the University Hospital of Blida. AKI was defined according to the KDIGO-2012 guidelines. Nutritional status was assessed using the Controlling Nutritional Status (CONUT) score. The association with in-hospital mortality was assessed using the Kaplan-Meier method and proportional Cox regression.ResultsAmong the 247 severely affected COVID-19 patients included in this study, 34.4% developed AKI, 30.4 and 1.2%, respectively, had moderate and severe CONUT scores, 17.7% worsened and progressed to a critical state and 26.7% did not survive. Both AKI and CONUT score were significantly associated with mortality in a dose-response manner (pLog-Rank < 0.0001). Their relative risks are respectively (HR = 3.25 CI 95% [1.99–5.3] and HR = 2.42 CI 95% [1.5–3.9], p < 0.0001). In multivariate analysis, the highest risk was observed for the AKI-CONUT-high combination (HR = 3.0, 95% CI [1.5–6.1], p = 0.002).ConclusionA possible synergistic interaction between AKI and CONUT score for COVID-19 short-term mortality has been highlighted. Monitoring of renal function associated with assessment of nutritional status should be performed routinely and systematically from the early stages of admission.     

Diffuse glomerular basement membrane lamellation in renal allografts from pediatric donors to adult recipients

The transplantation of kidneys from pediatric cadaveric donors into adult recipients is performed in many centers. However, some studies indicate that the outcome of such renal transplants may be inferior compared with that of adult donors, particularly if the donor is an infant. Morphologic studies of failed pediatric donor kidneys in adult recipients describe various degrees of segmental or global glomerular sclerosis. The authors have performed ultrastructural examinations on such transplants and have identified six cases with diffuse irregular lamellation of the glomerular basement membrane (GBM), a change that may develop as early as 10 weeks after transplantation. The age of all donors was < or =6 years; three were infants. The incidence of the lesion was 9% at our institution in renal transplant patients who received a graft from donors <10 years old. Diffuse GBM lamellation has not been found in renal transplants from adult donors. Light microscopy showed various degrees of diffuse mesangial expansion, usually with segmental glomerular sclerosis. The patients had severe proteinuria. While recurrent focal segmental glomerular sclerosis (FSGS) has to be excluded, such diffuse GBM lamellation is generally not seen in recurrent FSGS cases. The pathogenesis of the lesion is most likely related to hyperperfusion injury of small pediatric donor kidneys grafted into adult recipients.     

Left atrial size may predict exercise capacity and cardiovascular events in patients with heart failure

Our aim was to investigate, in patients with heart failure, the relationship between left atrial size and exercise capacity and cardiovascular events. Seventy-five patients (67 men and 8 women; mean age, 53.4 +/- 8.8 yr) with left ventricular ejection fractions of < or =0.45 (New York Heart Association functional classes I-III) were matched by age and sex with 20 healthy control subjects. Echocardiographic examinations were performed, as was exercise testing by the modified Bruce protocol. Patients were monitored for a period of 330 to 480 days for cardiac death or for heart failure that required hospitalization. The indexed left atrial diastolic size (beta level = -0.534, P <0.001) and left ventricular late diastolic filling velocity (beta level = 0.247, P <0.017) were the most important values in predicting low exercise capacity. The only independent predictor of low exercise capacity (<5 METS) was the indexed left atrial diastolic size (odds ratio, 1.428; 95% confidence interval, 1.09-1.702; P <0.001). Every 1 mm/m2 increase in indexed left atrial diastolic dimension caused a 42.8% increase in the risk of severe heart failure (exercise capacity, <5 METS). Independent predictors for cardiovascular events were indexed as left atrial systolic size (odds ratio, 1.383; 95% confidence interval, 1.145-1.671; P <0.001) and left ventricular early diastolic/late diastolic filling velocity (odds ratio, 1.096; 95% confidence interval, 1.010-1.189; P <0.027). Indexed left atrial diastolic and left atrial systolic size predict exercise capacity and cardiovascular events, respectively, in New York Heart Association functional class I through III heart failure patients.