Determinants and Reference Ranges of Serum Immunoglobulins in Middle-Aged and Elderly Individuals: a Population-Based Study

Purpose

In clinical practice, currently one reference range for serum immunoglobulin (Ig) A, G, and M is applied to all adults, although various factors may influence Ig serum levels. Population-based data on determinants of IgA, IgG, and IgM and recommendations for subgroup specific reference ranges are lacking. We aimed to provide an overview of determinants of IgA, IgG, and IgM in community-dwelling middle-aged and elderly individuals and explore determinants that influence Ig reference ranges.

Methods

Within the Rotterdam Study, we performed linear regression analyses for the association of demographic, lifestyle, and cardiovascular factors with serum IgA, IgG, and IgM. We furthermore calculated Ig reference ranges (based on percentiles), both overall and within relevant subgroups.

Results

We included 8768 participants (median age 62 years). IgA and IgG increased non-linearly with higher age (P?<?.0001 for both). Women had lower IgA (beta:???0.24; 95% confidence interval [95% CI]:???0.29;???0.20) and IgG (beta:???0.33; 95% CI:???0.44;???0.23), but higher IgM levels (beta: 0.08; 95% CI: 0.04;0.13) than men. Former and particularly current smoking were associated with lower IgA and IgG (betas between???0.07 and???1.03). Higher alcohol consumption was associated with lower IgG (beta for heavy drinking:???0.70; 95% CI:???0.91;???0.48). Corticosteroid use was associated with lower IgG (beta:???1.12; 95% CI:???1.58;???0.66). Associations with cardiovascular factors were heterogeneous and differed between sexes.

Conclusion

Age, sex, smoking, alcohol consumption, corticosteroid use, and cardiovascular factors are determinants that should be considered when interpreting serum Ig levels in middle-aged and elderly individuals and may require adjusted reference ranges.

     

The role of peer support education model on the quality of life and self-care behaviors of patients with myocardial infarction

ObjectiveThis study aimed to assess the effect of peer education on the quality of life and self-care behaviors of patients with myocardial infarction.MethodsIn this clinical trial, 70 patients with myocardial infarction meeting the inclusion criteria were assigned to experimental (n = 35) or control (n = 35) groups using block randomization. Patients in the intervention group received two one-hour training sessions on the third day after myocardial infarction during the CCU stay along with routine care. Education intervention was performed by peers. The control group will follow routine care. All patients selected were assessed using McNews' quality of life questionnaire and Miller self-care questionnaire, respectively before the intervention and also one month after discharge. Chi-square and t-test were used to analyze the data.ResultsAfter the intervention, the mean of quality of life and the mean score of self-care behaviors in the experimental group were significantly higher compared to the control group.ConclusionsAccording to the results, to improve the quality of life and promote the self-care behaviors in such patients, using peer education along with healthcare professionals is recommended.Practice ImplicationThis patient education approach had a significant impact on quality of life and self-care behavior.     

Effects of free and nanoparticulate curcumin on chemically induced liver carcinoma in an animal model

IntroductionCurcumin therapeutic applications are constrained by its prominent metabolic instability as well as inadequate absorption and bioavailability. The current study was designed to enhance the curcumin bioavailability by exploiting nanoparticles.Material and methodsEleven groups of mice were divided into: normal and nanoparticle control groups, a hepatocellular carcinoma (HCC) group induced by diethylnitrosamine (DEN), 2 groups treated with DEN plus a high dose/low dose of free curcumin, 2 groups treated with a high dose/low dose of free curcumin, 2 groups treated with DEN plus a high dose/low dose of nanoparticulate curcumin, and 2 groups treated with a high dose/low dose of nanoparticulate curcumin.ResultsDEN administration significantly increased liver enzymes, vascular endothelial growth factor, tumor necrosis factor-α, α-fetoprotein, malondialdehyde, and nucelar factor-κB. Also, it decreased serum albumin and tissue antioxidant activities and caused severe histological changes in hepatic tissue. Oral treatment of DEN-injected mice with either a high dose of free curcumin or the tested doses of nanoparticulate curcumin resulted in a significant improvement of all the tested parameters.ConclusionsAlthough the two tested doses of nanoparticulate curcumin were much lower than free curcumin, both doses were effective in preventing HCC development while the low dose of free curcumin was hardly effective. Hence, we conclude that nanoparticles enhance the bioavailability of curcumin.     

Bryostatin 1-induced modulation of nucleoside transporters and 2-chlorodeoxyadenosine influx in WSU-CLL cells

WSU-CLL cells, a fludarabine resistant B-cell chronic lymphocytic leukemia cell line, has been shown to exhibit enhanced sensitivity to 2-chlorodeoxyadenosine (2-CdA) following 48-72 h exposure to bryostatin 1. For 2-CdA to manifest its chemotherapeutic activity, it must first enter the cell through one of several specific nucleoside transporter systems. We present data to show that bryostatin 1-induced enhanced influx of 2-CdA is in part the result of bryostatin 1-induced modulation of nucleoside transporters in WSU-CLL cells. The bi-directional equilibrative NBMPR sensitive transporters in WSU-CLL cells were significantly down-regulated 90 min post-exposure to 1-200 nM bryostatin 1. This down-regulation was evident up to 144 h. In contrast, WSU-CLL cells exhibited a transient increase in Na+-dependent concentrative 2-CdA influx from 48 to 96 h after bryostatin 1 exposure which was evident for a longer duration than that accounted for by the increase in deocycytidine kinase activity. These data may, in part, explain the enhanced efficacy of 2-CdA seen in WSU-CLL cells following 48-72 h exposure to bryostatin 1. It may raise questions as to the importance of the bi-directional transporters in determining the resistance or sensitivity of CLL cells to 2-CdA or other nucleoside analogues.     

A systemic review of barriers to accessing paediatric eye care services in African countries

BackgroundGlobal estimate reported that 1.4 million children are blind of which three-quarters live in developing countries. Childhood Visual Impairment is a major public health problem globally especially in rural areas of developing countries.ObjectiveTo review barriers to accessing paediatric eye care services in African countriesMethodsThe studies in this review were searched in online databases (PubMed, Web of Sciences, ProQuest, Scopus, Google Scholar, African Index Medicus and Medline) for studies published between January 2000 and April 2020. The articles included in this review, which was conducted in Africa to assess the barriers for accessing paediatric eye care services with regards availability, accessibility, affordability, socio cultural barriers of parents/caregivers and community.ResultsOf 22 705 articles screened, the study found 29 publications from 10 African countries which met the inclusion criteria. The main barriers were non-availability, non-accessibility, and non-affordability of paediatric eye care services. The studies reviewed revealed that there are other factors affecting the utilization of paediatric eye services which include the primary health system, geographic barriers, health beliefs, perception of parents; lack of knowledge, attitudes and practices about paediatric eye care. Furthermore, environmental, demographic barriers and socio-economic status has negative impact on accessing paediatric eye care services in African counties.ConclusionThe main barriers to accessing paediatric eye care services in Africa were affordability, accessibility and availability. There is therefore a need for all relevant stakeholders to play a significant role in addressing barriers to child eye care in African countries.     

Lactobacillus acidophilus Induces a Strain-specific and Toll-Like Receptor 2–Dependent Enhancement of Intestinal Epithelial Tight Junction Barrier and Protection Against Intestinal Inflammation

Defective intestinal tight junction (TJ) barrier is an important pathogenic factor of inflammatory bowel disease. To date, no effective therapies that specifically target the intestinal TJ barrier are available. The purpose of this study was to identify probiotic bacterial species or strains that induce a rapid and sustained enhancement of intestinal TJ barrier and protect against the development of intestinal inflammation by targeting the TJ barrier. After high-throughput screening of >20 Lactobacillus and other probiotic bacterial species or strains, a specific strain of Lactobacillus acidophilus, referred to as LA1, uniquely produced a marked enhancement of the intestinal TJ barrier. LA1 attached to the apical membrane surface of intestinal epithelial cells in a Toll-like receptor (TLR)-2–dependent manner and caused a rapid increase in enterocyte TLR-2 membrane expression and TLR-2/TLR-1 and TLR-2/TLR-6 hetero-complex–dependent enhancement in intestinal TJ barrier function. Oral administration of LA1 caused a rapid enhancement in mouse intestinal TJ barrier, protected against a dextran sodium sulfate (DSS) increase in intestinal permeability, and prevented the DSS-induced colitis in a TLR-2– and intestinal TJ barrier–dependent manner. In conclusion, we report for the first time that a specific strain of LA causes a strain-specific enhancement of intestinal TJ barrier through a novel mechanism that involves the TLR-2 receptor complex and protects against the DSS-induced colitis by targeting the intestinal TJ barrier.

Intestinal epithelial tight junctions (TJs) are the apical-most junctional complexes and act as a functional and structural barrier against the paracellular permeation of harmful luminal antigens, which promote intestinal inflammation.¹ The increased intestinal permeability caused by defective intestinal epithelial TJ barrier or a leaky gut is an important pathogenic factor that contributes to the development of intestinal inflammation in inflammatory bowel disease (IBD) and other inflammatory conditions of the gut, including necrotizing enterocolitis and celiac disease.^2,3 Clinical studies in patients with IBD have found that a persistent increase in intestinal permeability after clinical remission is predictive of poor clinical outcome and early recurrence of the disease, whereas normalization of intestinal permeability correlates with a sustained long-term clinical remission.4, 5, 6 Accumulating evidence has found that a defective intestinal TJ barrier plays an important role in exacerbation and prolongation of intestinal inflammation in IBD. Currently, no effective therapies that specifically target the tightening of the intestinal TJ barrier are available.Intestinal microbiota play an important role in modulating the immune system and in the pathogenesis of intestinal inflammation.⁷ Patients with IBD have bacterial dysbiosis in the gut, characterized by a decrease in bacterial diversity and an aberrant increase in some commensal bacteria, which are an important factor in the pathogenesis of intestinal inflammation.^8,9 Normal microbial flora of the gastrointestinal tract consists both of bacteria that are known to have beneficial effects (probiotic bacteria) on intestinal homeostasis and bacteria that could potentially have detrimental effects on gut health (pathogenic bacteria).¹⁰ The modulation of intestinal microflora affects the physiologic and pathologic states in humans and animals. For example, fecal transplantation from healthy, unaffected individuals to patients with refractory Clostridium difficile colitis is curative in up to 94% of the treated patients, and transfer of stool microbiome from obese mice induces obesity in previous lean mice, whereas transfer of microbiome from lean mice preserves the lean phenotype.11, 12, 13 The beneficial effects of gut microbiota are host and bacterial species-specific.¹⁴ Although multiple studies indicate that some commensal bacteria play a beneficial role in gut homeostasis by preserving or promoting the intestinal barrier function, because of conflicting reports, it remains unclear which probiotic species cause a persistent predictable enhancement in the TJ barrier and could be used to treat intestinal inflammation by targeting the TJ barrier. For example, some studies suggest that Lactobacillus acidophilus, Lactobacillus casei, Lactobacillus plantarum, or Lactobacillus rhamnosus cause a modest enhancement in the intestinal epithelial TJ barrier, whereas others have found minimal or no effect of these probiotic species on the intestinal TJ barrier.15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25 The major aim the current study was to perform a high-throughput screening of Lactobacillus and other bacterial species to identify probiotic species that induce a rapid, predictable, and marked increase in the intestinal epithelial TJ barrier and protect against the development of intestinal inflammation by preserving the intestinal TJ barrier.In the studies described herein, most of the probiotic species tested (>20 species or strains) had a modest or minimal effect on intestinal TJ barrier function. L. acidophilus uniquely caused a rapid and marked increase in intestinal TJ barrier function. Further analysis indicated that the effect of L. acidophilus was strain-specific, limited to a specific strain of L. acidophilus, and did not extend to other L. acidophilus strains. The L. acidophilus enhancement of the intestinal TJ barrier was mediated by live bacterial-enterocyte interaction that involved Toll-like receptor (TLR)-2 heterodimeric complexes on the apical membrane surface of intestinal epithelial cells. Our animal studies also found that L. acidophilus causes a marked enhancement in mouse intestinal barrier function and protects against the dextran sodium sulfate (DSS)–induced colitis by preserving and augmenting the mouse intestinal barrier function in a strain-specific manner.     

Effects of diabetes on myocardial capillary density and serum angiogenesis biomarkers in male rats

INTRODUCTION:

Cardiovascular disease is one of the main causes of mortality and morbidity in diabetic patients. This study evaluated the effects of diabetes on myocardial capillary density and several serum angiogenic factors including nitric oxide, vascular endothelial growth factor, and soluble vascular endothelial growth factor receptors.

METHODS:

Twelve male rats were divided into two groups: control and diabetic (n = 6 each). Diabetes was induced with a single dose of streptozotocin (50 mg/kg). After 21 days, capillary density in the myocardial tissue was evaluated using immunohistochemical staining and is reported as capillaries per mm². Blood samples were collected before and after the induction of diabetes.

RESULTS:

In the diabetic group, serum nitric oxide and soluble vascular endothelial growth factor receptor 2 concentrations were lower than the levels in the control group, while the level of soluble vascular endothelial growth factor receptor 1 was significantly higher. There was no significant change in the serum vascular endothelial growth factor concentration between the diabetic and control groups; however, the ratio of vascular endothelial growth factor to vascular endothelial growth factor receptor 1 was significantly lower in the diabetic animals. The myocardial capillary density was also lower in the diabetic group compared with the control group (1549±161 vs. 2156±202/mm², respectively).

CONCLUSION:

Reduced serum nitric oxide and vascular endothelial growth factor receptor 2 levels, increased serum vascular endothelial growth factor receptor 1 levels and a lower vascular endothelial growth factor to vascular endothelial growth factor receptor 1 ratio may be responsible for the decreased myocardial capillary density in diabetic rats.     

Molecular characterization of CTX-Mβ-lactamases among Klebsiella pneumoniae isolated from patients at Tehran hospitals

Purpose: Plasmid-encoded CTX-M-group of extended-spectrum β-lactamases (ESBLs) represent a significant and rapidly emerging problem in most part of the world. The aim of the present study was to describe the prevalence of CTX-M producing Klebsiella pneumoniae at Tehran hospitals. Materials and Methods: Clinical isolates of K. pneumoniae (n=250) were collected from 10 hospitals of Tehran. Susceptibility to antimicrobial agents, MIC of cefotaxime and ESBLs production of collected isolates were detected. All ESBL-producing isolates were screened for bla_CTX-M genes using PCR and DNA sequencing. Molecular typing of bla_CTX-M harboring isolates was performed by Pulsed–field gel electrophoresis assay. Results: Of 250 K. pneumoniae clinical isolates, 102 isolates revealed ESBLs – phenotype. PCR assay and sequencing detected bla_CTX-M genes in 71.5% (n= 73) of ESBL-producing isolates. The prevalence of CTX-M -I and CTX-M-III clusters among these isolates was 35.61% (n=26) and 21.9 % (n=16) respectively. Coexistence of CTX-M -I and CTX-M-III clusters was found among 42.5% (n= 31) of isolates. Of 102 isolates that were positive in the phenotypic confirmatory test (PCT), 29 isolates (28.4%) did not produce any amplicons in PCR for bla_CTX-M gene. The results of PCR for CTX-M -II and CTX-M-IV clusters were also negative. Analysis of the 31 CTX-M producing K. pneumoniae isolates by PFGE typing showed 26 distinct patterns. Conclusions: The bla_CTX-M genes are widespread among Iranian isolates of K. pneumoniae. PFGE demonstrated the high diversity of K. pneumoniae harboring bla_CTX-M in our study.     

Correlation between E-cadherin and CD44 adhesion molecules expression and cervical lymph node metastasis in oral tongue SCC: Predictive significance or not

The aim of this article was to evaluate the expression of E-cadherin and CD44 adhesion molecule in oral tongue squamous cell carcinoma (SCC) since inappropriate expression of adhesion molecules raises the metastatic ability of the tumor cells.Biopsy specimens from 92 patients with tongue SCC were examined for the expression of E-cadherin and CD44 by immunohistochemistry. The relationship of immunoreactivity with tumor stage and cervical lymph node metastasis was then analyzed.Sixty-one patients (66.3%) had reduced or negative staining for CD44. Weak or absent staining for E-cadherin was seen in 14 patients (15.21%). Cervical lymph node metastasis is associated with decreased or negative staining for CD44, but no association was found between E-cadherin immunoreactivity and nodal metastasis.Our study reveals that reduced expression of CD44 could be an indicator of high invasiveness of tumor by increasing cervical lymph node metastasis.