Hookworm Anemia: Iron Metabolism and Erythrokinetics

Iron metabolism, balance of red cell production and destruction and ironabsorption from hemoglobin were determined in 11 patients with heavy hookworm infection and severe anemia.

The plasma iron, total iron binding capacity, bone marrow hemosiderinand plasma Fe⁵⁹ clearance are in agreement with the idea that the anemia associated with hookworm infection is of the iron deficiency type.

The rate of red cell production measured by the E/M ratio, absolute reticulocyte count and plasma iron turnover showed an increase to about twicenormal, while the rate of destruction estimated by the T erythrocytesurvival showed a destruction about 5 times normal. This unbalance betweenproduction and destruction could explain the severity of the anemia.

The increase of fecal urobilinogen output to twice normal was interpretedas due to the metabolism of the hemoglobin lost into the intestine rather than toan increase of hemolysis.

The estimation of fecal blood loss in the patients whose red cells weretagged with Cr⁵¹ and Fe⁵⁹, showed that the radioactivity counted with Fe⁵⁹was only about 63 per cent of the radioactivity counted with Cr⁵¹. This difference was interpreted as due to iron absorption from the hemoglobin lostinto the intestine.

The mean daily fecal excretion of iron reaches 4.7 mg. Since the ironmetabolism in these patients is in equilibrium, we have concluded that theiron loss is replaced by the iron from food; this is in addition to the 3 mg.hemoglobin iron which is reabsorbed from the blood lost into the gut.

Submitted on January 9, 1961 Accepted on April 2, 1961     

Biosynthesis of proopiomelanocortin-derived peptides in prohormone convertase 2 and 7B2 null mice

Prohormone convertases (PCs) are thought to represent the major proteinases involved in the biosynthetic processing of peptide hormone precursors to bioactive peptide products. The maturation of PC2 requires the aid of a helper protein, 7B2, in order for the zymogen to become an active enzyme species. The 7B2 and PC2 nulls should thus be functionally equivalent with regard to deficits in precursor processing. In this article, we have examined this proposition through the study of proopiomelanocortin (POMC) biosynthesis and granule content in both null models. RIA data indicate that both PC2 and 7B2 nulls lack pituitary alpha-MSH; interestingly, 7B2 nulls are still able to generate beta-endorphin from beta-lipotropin, whereas PC2 nulls contain little if any beta-endorphin. Labeling experiments demonstrate a build-up of POMC, high molecular weight intermediates, and intact ACTH, as well as the disappearance of alpha-MSH, in both null models. Electron microscopy of neurointermediate lobe melanotrophs reveals the presence of a significantly greater number of secretory granules in both 7B2 and PC2 nulls compared with wild-type controls. However, PC2 null melanotrophs contain twice as many granules as 7B2 null melanotrophs. Another difference between the two null models is a relatively enhanced accumulation of precursors in the PC2 null compared with the 7B2 null; these include not only PC2 substrates, but also presumed PC1 substrates. These data indicate that the two nulls are not phenotypically equivalent.     

Membrane adaptation limitations in Enterococcus faecalis underlie sensitivity and the inability to develop significant resistance to conjugated oligoelectrolytes

The growing problem of antibiotic resistant bacteria, along with a dearth of new antibiotics, has redirected attention to the search for alternative antimicrobial agents. Conjugated oligoelectrolytes (COEs) are an emerging class of antimicrobial agents which insert into bacterial cell membranes and are inhibitory against a range of Gram-positive and Gram-negative bacteria. In this study, the extent of COE resistance that Enterococcus faecalis could achieve was studied. Enterococci are able to grow in hostile environments and develop resistance to membrane targeting antibiotics such as daptomycin in clinical settings. Herein we expand our knowledge of the antimicrobial mechanism of action of COEs by developing COE-resistant strains of E. faecalis OG1RF. Evolution studies yielded strains with a moderate 4–16 fold increase in antimicrobial resistance relative to the wild type. The resistant isolates accumulated agent-specific mutations associated with the liaFSR operon, which is a cell envelope-associated stress-response sensing and regulating system. The COE resistant isolates displayed significantly altered membrane fatty acid composition. Subsequent, exogenous supplementation with single fatty acids, which were chosen based on those dominating the fatty acid profiles of the mutants, increased resistance of the wild-type E. faecalis to COEs. In combination, genetic, fatty acid, and uptake studies support the hypothesis that COEs function through insertion into and disruption of membranes and that the mechanism by which this occurs is specific to the disrupting agent. These results were validated by a series of biophysical experiments showing the tendency of COEs to accumulate in and perturb adapted membrane extracts. Collectively, the data support that COEs are promising antimicrobial agents for targeting E. faecalis, and that there is a high barrier to the emergence of severely resistant strains constrained by biological limits of membrane remodeling that can occur in E. faecalis.

COEs are emerging antimicrobials to combat drug resistant infections and to which bacteria develop only limited resistance.     

A Case Report of Ablepharon-Macrostomia Syndrome with Amniotic Membrane Grafting

We describe a rare case of an infant who was born with multiple congenital anomalies, including the absence of eyelids. This patient had many dysmorphic features consistent with a severe phenotype of ablepharon-macrostomia syndrome (AMS) including a fish-like appearance of the mouth, rudimentary ears, absence of body hair, thin skin, absent nipples, abdominal distension, and genital abnormalities. Upon presentation, there was severe exposure keratopathy causing large bilateral sterile ulcers culminating in corneal melting of both eyes. An amniotic membrane graft was used to attempt to maintain the corneal surface integrity. However, because of the late presentation, the corneas could not be salvaged. Extensive surgical reconstruction of both eyelids and bilateral penetrating keratoplasty was ultimately performed successfully to protect the ocular surfaces while trying to maximize the visual potential. Early amniotic membrane grafting may be done at the bedside and may help preserve the ocular in patients with severe eyelid deformities until more definitive treatment is performed.Key Words: Ablepharon, Macrostomia, Congenital eyelid anomalies, Absent hair, Absent eyelids     

Optimizing insulin pump therapy: the potential advantages of using a structured diabetes management program

Use of continuous subcutaneous insulin infusion (CSII) therapy improves glycemic control, reduces hypoglycemia and increases treatment satisfaction in individuals with diabetes. As a number of patient- and clinician-related factors can hinder the effectiveness and optimal usage of CSII therapy, new approaches are needed to address these obstacles.

Ceriello and colleagues recently proposed a model of care that incorporates the collaborative use of structured SMBG into a formal approach to personalized diabetes management within all diabetes populations. We adapted this model for use in CSII-treated patients in order to enable the implementation of a workflow structure that enhances patient–physician communication and supports patients’ diabetes self-management skills.

We recognize that time constraints and current reimbursement policies pose significant challenges to healthcare providers integrating the Personalised Diabetes Management (PDM) process into clinical practice. We believe, however, that the time invested in modifying practice workflow and learning to apply the various steps of the PDM process will be offset by improved workflow and more effective patient consultations. This article describes how to implement PDM into clinical practice as a systematic, standardized process that can optimize CSII therapy.     

Total fluid intake of children and adolescents: cross-sectional surveys in 13 countries worldwide

Purpose

To describe total fluid intake (TFI) according to socio-demographic characteristics in children and adolescents worldwide.

Methods

Data of 3611 children (4–9 years) and 8109 adolescents (10–18 years) were retrieved from 13 cross-sectional surveys (47 % males). In three countries, school classes were randomly recruited with stratified cluster sampling design. In the other countries, participants were randomly recruited based on a quota method. TFI (drinking water and beverages of all kinds) was obtained with a fluid-specific record over 7 consecutive days. Adequacy was assessed by comparing TFI to 80 % of adequate intake (AI) for total water intake set by European Food Safety Authority. Data on height, weight and socio-economic level were collected in most countries.

Results

The mean (SD) TFI ranged from [1.32 (0.68)] to [1.35 (0.71)] L/day. Non-adherence to AIs for fluids ranged from 10 % (Uruguay) to >90 % (Belgium). Females were more likely to meet the AIs for fluids than males (4–9 years: 28 %, OR 0.72, p = 0.002; 10–18 years: 20 %, OR 0.80, p = 0.001), while adolescents were less likely to meet the AI than children (OR 1.645, p < 0.001 in males and OR 1.625, p < 0.001 in females).

Conclusions

A high proportion of children and adolescents are at risk of an inadequate fluid intake. This risk is especially high in males and adolescents when compared with females or children categories. This highlights water intake among young populations as an issue of global concern.

     

Echocardiographic evaluation of pulmonary hypertension,right ventricular function,and right ventricular-pulmonary arterial coupling in patients with rheumatoid arthritis

Clinical Rheumatology - Rheumatoid arthritis (RA) patients are at increased risk for developing cardiovascular disease, including right heart failure. The evaluation of right ventricle (RV) using...     

Determinants of ST-segment elevation myocardial infarction as clinical presentation of acute coronary syndrome

Journal of Thrombosis and Thrombolysis - Antiplatelet agents and statin therapies are widely used in patients with known cardiovascular disease. Plaque rupture (PR) and plaque erosion (PE) are the...     

Low Quality of Life,Falls, and Pre-Frailty are Associated with Depressive Symptoms in Virologically Suppressed PLWHIV in Salvador,Brazil

AIDS and Behavior - Depression is the leading cause of years lived with disability worldwide and PLWHIV present a higher risk of developing depressive symptoms. We aimed to evaluate depressive...