Cell-mediated immune responses to antigens of Bordetella pertussis and protection against pertussis in school children

BACKGROUND: Increasing evidence suggests that cell-mediated immunity (CMI) is involved in immune response against Bordetella pertussis. However, there are practically no studies evaluating the significance of pertussis-specific CMI in relation to protection against clinical pertussis. METHODS: An outbreak of pertussis was studied prospectively in 13-year-old pupils in a rural school. B. pertussis infection was diagnosed by culture, microagglutination and enzyme immunoassay serology with the use of pertussis toxin, filamentous hemagglutinin and pertactin as antigens. Pertussis-specific CMI responses were assessed by in vitro proliferation assay of peripheral blood mononuclear cells. RESULTS: At the initial sampling 7 of 22 children had symptoms suggestive of pertussis and 15 were asymptomatic. Of the latter 3 remained healthy, 8 were later confirmed to have had asymptomatic infection, 3 developed laboratory-confirmed pertussis and 1 developed cough without laboratory evidence of pertussis. Initial in vitro proliferations of peripheral blood mononuclear cells induced by pertussis toxin, filamentous hemagglutinin and/or pertactin were positive in all 3 healthy children, in 6 of 8 children who had asymptomatic infection, but in none of the 3 children who later developed pertussis. Although some children who remained healthy had high values of antibodies, no clear association was found between initial serum antibody values and clinical outcome. CONCLUSIONS: These preliminary data suggest that CMI may have an important role in protection against clinical pertussis but do not exclude a role for antibodies. Furthermore the results stress a multifactorial nature of the immune protection against B. pertussis.     

Peripheral retinal neovascularization in talc retinopathy.

BACKGROUND: Neovascularization of the peripheral retina can be present in a number of systemic and ocular diseases. Very rarely, peripheral retinal neovascularization can also be manifested in intravenous drug abusers. In addition to ocular complications, intravenous drug abusers are at high risk for contracting various infections and the development of pulmonary and cardiovascular diseases. We present a case of a chronic heroin and cocaine abuser with bilateral peripheral retinal neovascularization, pulmonary complications, and a history of endocarditis. CASE REPORT: A patient with a 20-year history of heroin and cocaine abuse initially presented for a routine eye examination. Fundus examination revealed pinpoint white deposits centered in both maculas, engorged vascular fronds with a patch of intraretinal hemorrhage in the peripheral retinal of the right eye and neovascularization of the disc as well as exudation with adjacent focal preretinal hemorrhage in the left eye. The patient underwent fluorescein angiography and was screened for diabetes, sarcoidosis, and sickle cell disease. When no systemic disease could be discovered, it was concluded that the peripheral retinal neovascularization developed as a result of vascular occlusion from heroin and cocaine abuse. DISCUSSION: It is important to investigate the cause of neovascularization in the peripheral retina. Retinal vascular emboli such as talc are common in drug abusers, but in most cases, the retinal deposits pose only a minimal threat to vision. However, this case shows that careful retinal examination is warranted in drug abusers to rule out neovascularization of the retina. Other causes of peripheral retinal neovascularization should be ruled out as well. These conditions include sickle cell retinopathy, sarcoidosis, diabetic retinopathy, blood dyscrasias, retinal vascular occlusion, Eales' disease, and other systemic conditions, so that appropriate ocular and systemic treatment can be provided. Peripheral retinal neovascularization is best treated by pan-retinal photocoagulation.     

Carthamus tinctorius L. extract activates insulin‐like growth factor‐I receptor signaling to inhibit FAS‐death receptor pathway and suppress lipopolysaccharides‐induced H9c2 cardiomyoblast cell apoptosis

Carthamus tinctorius L. (Compositae) is used in Chinese medicine to treat heart disease and inflammation. In our previous study, we found that C. tinctorius L. inhibited lipopolysaccharides (LPS)‐induced tumor necrosis factor‐alpha (TNF‐α) activation, JNK expression, and apoptosis in H9c2 cardiomyoblast cells. The present study was performed to investigate the protective effect of C. tinctorius extract (CTF) on LPS‐challenged H9c2 myocardioblast cell and to explore the possible underlying mechanism. Cell viability assay showed that LPS treatment decreased the cell viability of H9c2 cell, whereas CTF treatment reversed LPS cytotoxicity in a dose‐dependent manner, especially in the LPS + CTF 25 (μg/mL) group. LPS treatment‐induced apoptosis was determined by transferase‐mediated dUTP nick end labeling assay, and by Western blot. LPS‐induced apoptotic bodies were decreased following CTF treatment. Expression of TNF‐α, FAS‐L, FAS, FADD, caspase‐8, BID, and t‐BID was significantly increased in LPS‐treated H9c2 cells. In contrast, it was significantly suppressed by the administration of CTF extract. In addition, CTF treatment activates antiapoptotic proteins, Bcl‐2 and p‐Bad, and downregulates Bax, cytochrome‐c, caspase‐9, caspase‐3, and apoptosis‐inducing factor expression. Furthermore, CTF exerted cytoprotective effects by activating insulin‐like growth factor‐I (IGF‐I) signaling pathway leading to downregulation of the apoptotic proteins involved in FAS death receptor pathway. In addition, AG1024 and IGF‐I receptor (IGF‐IR) inhibitor and siRNA silencing reverses the effect of CTF implying that CTF functions through the IGF‐IR pathway to inhibit LPS‐induced H9c2 apoptosis. These results suggest that treatment with CTF extract prevented the LPS‐induced apoptotic response through IGF‐I pathway.     

Association between Micronutrient Intake and Breast Cancer Risk According to Body Mass Index in South Korean Adult Women: A Cohort Study

This study investigated the association between micronutrient intake and breast cancer risk in South Korean adult women. This association was stratified according to body mass index (BMI) categories. Data from the Korean Genome and Epidemiology Study (KoGES) and the Health Examinee Study were analyzed. Altogether, 63,337 individuals (aged ≥40 years) completed the baseline and first follow-up surveys; 40,432 women without a history of cancer at baseline were included in this study. The association between micronutrient intake and breast cancer was determined by estimating the hazard ratio (HR) and 95% confidence interval (CI) using the Cox proportional hazard regression model. A stratified analysis by BMI (<25 kg/m² and ≥25 kg/m²) was performed. The an analysis of 15 micronutrients and breast cancer risk revealed that none of the micronutrients were associated with breast cancer risk after adjusting for covariates. In obese women, the risk of breast cancer was significantly reduced in the group that consumed vitamin C more than the recommended level (HR = 0.54, 95% CI: 0.31–0.93) and vitamin B6 levels above the recommended level (HR = 0.48, 95% CI: 0.25–0.89). In obese women, exceeding the recommended daily intake levels of vitamin C and vitamin B6 was associated with a lower risk of breast cancer. However, other micronutrients were not associated with breast cancer risk in these women.     

Clinical and genetic features of congenital bile acid synthesis defect with a novel mutation in AKR1D1 gene sequencing: Case reports

Rationale:Congenital bile acid synthesis defect (BASD) is a rare disease caused by mutations in the aldo-keto reductase 1D1 gene, which encodes the primary Δ4-3-oxosteroid 5β-reductase enzyme. Early disease diagnosis is critical for early treatment with bile acid replacement therapy, with an excellent chance for recovery. In contrast, protracted diagnosis and treatment may lead to poor outcomes, including decompensated hepatic cirrhosis, liver transplant, and even death.Patient concerns:Three clinical congenital bile acid synthesis defect cases in the Vietnamese population are herein reported. These pediatric patients presented with symptoms of prolonged postpartum jaundice and abnormal loose stool (mucus, lipids, and white). The clinical examinations showed hepatosplenomegaly. Urinalysis showed a very low fraction of primary bile acids and atypical 3-oxo-Δ4- bile acids in all three patients.Diagnoses:The patients were diagnosed with primary Δ4-3-oxosteroid 5β-reductase deficiency. Next-generation gene sequencing revealed two homozygous mutations in the aldo-keto reductase family 1 member D1 gene. The first is a documented variant, c.797G>A (p.Arg266Gln), and the second is a novel mutation at c.155T>C (p.Ile52Thr).Interventions:Immediately after diagnosis, patients were treated with oral chenodeoxycholate 5 mg/kg/d.Outcomes:The patients’ symptoms, signs, and primary bile acids levels improved significantly.Lessons:Clinicians should consider genetic disorders related to cholestasis for effective and life-saving treatment. A prompt genetic analysis by next-generation gene sequencing enables patients to access bile acid replacement therapy earlier, significantly improving short- and long-term outcomes.     

Stilbenes and oligostilbenes from leaf and stem of <Emphasis Type="Italic">Vitis amurensis</Emphasis> and their cytotoxic activity

Chromatographic separation of the EtOAc fraction from the leaf and stem of Vitis amurensis led to the isolation of six oligostilbenoids (i.e., r-2-viniferin (1), trans-amurensin B (2), trans-ɛ-viniferin (3), gnetin H (4), amurensin G (5), (+)-ampelopsin A (8)) and four stilbenoids (i.e., trans-resveratrol (6), (+)-ampelopsin F (7), piceatannol (9), and trans-piceid (10)). The structures have been identified on the basis of spectroscopic evidence and physicochemical properties. The isolates were investigated for cytotoxic activity against three cancer cell lines in vitro using the MTT assay method. Amurensin G (5) and trans-resveratrol (6) showed significant cytotoxic activity against L1210, K562 and HTC116 cancer cell lines with IC₅₀ values ranging from 15.7 ± 2.1 to 30.9 ± 1.8 μM. (+)-Ampelopsin A (8) and trans-piceid (10) exhibited considerable cytotoxic activity against L1210 (IC₅₀ values of 30.6 ± 4.1 and 28.7 ± 2.81 μM, respectively) and K562 (IC₅₀ values of 38.6 ± 0.82 and 24.6 ± 0.76 μM, respectively). Gnetin H (4) showed only weak cytotoxic activity against L1210 with an IC₅₀ value of 40.1 ± 4.23 μM. On the other hand, r-2-viniverin (1), trans-amurensin B (2), trans-ɛ-viniferin (3), (+)-ampelopsin F (7), and piceatannol (9) exhibited no activity on three cancer cell lines.     

Puerarin activates endothelial nitric oxide synthase through estrogen receptor-dependent PI3-kinase and calcium-dependent AMP-activated protein kinase

The cardioprotective properties of puerarin, a natural product, have been attributed to the endothelial nitric oxide synthase (eNOS)-mediated production of nitric oxide (NO) in EA.hy926 endothelial cells. However, the mechanism by which puerarin activates eNOS remains unclear. In this study, we sought to identify the intracellular pathways underlying eNOS activation by puerarin. Puerarin induced the activating phosphorylation of eNOS on Ser1177 and the production of NO in EA.hy926 cells. Puerarin-induced eNOS phosphorylation required estrogen receptor (ER)-mediated phosphatidylinositol 3-kinase (PI3K)/Akt signaling and was reversed by AMP-activated protein kinase (AMPK) and calcium/calmodulin-dependent kinase II (CaMKII) inhibition. Importantly, puerarin inhibited the adhesion of tumor necrosis factor (TNF)-α-stimulated monocytes to endothelial cells and suppressed the TNF-α induced expression of intercellular cell adhesion molecule-1. Puerarin also inhibited the TNF-α-induced nuclear factor-κB activation, which was attenuated by pretreatment with N^G-nitro-l-arginine methyl ester, a NOS inhibitor. These results indicate that puerarin stimulates eNOS phosphorylation and NO production via activation of an estrogen receptor-mediated PI3K/Akt- and CaMKII/AMPK-dependent pathway. Puerarin may be useful for the treatment or prevention of endothelial dysfunction associated with diabetes and cardiovascular disease.     

Fetal pulse oxymetry

Labor is monitored to avoid per partum asphyxia and its consequences. Cardiotocography enables asphyxia detection but carries unuseful cesarean sections. When cardiotocography is not reassuring, fetal pulse oxymetry makes it possible to reduce cesarean section rate for non-reassuring fetal status. Nevertheless, there is an increased number of cesarean sections for dystocia that could be due to the presence of the oxygen sensor itself. A global reduction is mainly observed when oxymetry is associated with fetal blood sampling for pH measurement. In this case, oxymetry also makes it possible to reduce the number of necessary samplings.