Galectin-3: a new biomarker for differentiating periodic fever, adenitis, pharyngitis, aphthous stomatitis (PFAPA) syndrome from familial Mediterranean fever?

Differentiating PFAPA (periodic fever, aphthosis, pharyngitis, and adenitis) syndrome from familial Mediterranean fever (FMF) could be challenging in some cases. Galectin-3 is a lectin with regulatory functions in apoptosis and inflammation. We aimed to test whether galectin-3 could be a biomarker for differentiating PFAPA syndrome from FMF. Patients with PFAPA syndrome, FMF, cryopyrin-associated periodic syndrome (CAPS), and streptococcal pharyngitis, and healthy controls were included in this study. Serum galectin-3 levels were measured using enzyme-linked immunosorbent assay. Eighty-seven patients (36 with PFAPA, 39 with FMF, 8 with CAPS, 4 with streptococcal pharyngitis), and 17 healthy controls were included. Blood samples were drawn during attacks from 20 PFAPA and 7 FMF patients and attack-free periods from 22 PFAPA, 35 FMF, and 8 CAPS patients. The median serum galectin-3 level in the PFAPA-attack group (1.025 ng/ml) was significantly lower than the levels in healthy control (2.367 ng/ml), streptococcal pharyngitis (3.021 ng/ml), FMF attack (2.402 ng/ml), and FMF-attack-free groups (2.797 ng/ml) (p = 0.006, 0.03, 0.01, and < 0.001, respectively). PFAPA-attack-free group had lower galectin-3 levels than the FMF-attack-free group (1.794 vs. 2.797 ng/ml, respectively; p = 0.01). Galectin-3 levels did not differ significantly between CAPS and attack-free PFAPA patients (1.439 ng/ml vs. 1.794 ng/ml, respectively; p = 0.63). In our study, for the first time, we defined galectin-3 as a promising biomarker that differs between PFAPA and FMF patients during both disease flares and attack-free periods. Further studies with high number of patients could validate its role as a biomarker.

Correlation between human health and reactive oxygen species produced in blood: a long-term chemiluminescence and fluorescence analysis.

The previous slide-glass type system could simultaneously detect reactive and highly reactive oxygen species, i.e., superoxide radicals (O2-·) and hypochlorite ions (OCl-) elicited from leucocytes in sample blood, but had some drawbacks, i.e., signal noise from air-flow stirring, potential biohazard risks, etc. because of open samples placed on a slide glass. We overcame these drawbacks by adopting a fluidic-chip container in a new system, which resulted in higher sensitivity and more stable measurements. Using the new system, we conducted a pilot study on nominally healthy volunteers to find whether or not the monitored activities of leukocytes can distinguish more or less unhealthy conditions from healthy ones. At first, healthy volunteers of both genders and of various ages showed that the fluctuation magnitudes (%) of O2-· and OCl- were nearly similar to each other and to that of the neutrophil count fluctuation. These parameters sometimes exceeded the healthy fluctuation range. By comparing these large fluctuations with the data of an inflammation marker C-reactive protein (CRP), the neutrophil count fluctuation and the timings/symptoms of abnormalities found in questionnaire, we could gain information suggesting the factors causing the large fluctuations. The new system could detect bodily abnormalities earlier than CRP or self-aware symptoms.

High or low temperature extraction, which is more conducive to Triphala against chronic pharyngitis?

OBJECTIVE: Explore the effects of high-temperature reflux extraction and low-temperature decompressing inner ebullition on Triphala's chemical composition and anti-chronic pharyngitis activity. METHODS: The network pharmacology was used to analyze the material basis, targets and pathways of Triphala for chronic pharyngitis. HPLC were used to compare the fingerprint profile and content of components between the two extracts. The antioxidant and anti-chronic pharyngitis activities of the two extracts were compared by DPPH assay and ammonia induced chronic pharyngitis model in rats. RESULTS: The network pharmacology results showed that the active ingredients of Triphala for chronic pharyngitis are epigallocatechin-3-gallate, (+)-catechin, epicatechin, epicatechin gallate, (+)-gallocatechin, quercetin, luteolin, leucodelphinidin and other flavonoids; phenolic acids such as gallic acid and ellagic acid; alkaloids such as ellipticine, cheilanthifoline; hydrolyzed tannins such as corilagin and chebulic acid. The high-temperature reflux extract and the low-temperature decompressing inner ebullition extract have extremely significant differences in the fingerprint profile. Among them, the content of gallic acid, ellagic acid, chebulic acid, catechin, epicatechin, corilagin, quercetin, and epicatechin gallate in the reflux extract is 1.1-5.3 times as much as decompressing inner ebullition extract. The free radical scavenging ability of reflux extract is significantly stronger than that of decompression extract (p < 0.01), and it has a repairing effect on pharyngeal mucosal damage (reducing keratinization or hyperplasia of mucosal epithelium, reducing inflammatory cell infiltration and bleeding), and reducing IL-1ß (P＜0.05), IL-6 (p＜0.05), TNF-α overexpression ability is stronger than the decompressing inner ebullition extract. CONCLUSIONS: gallic acid, ellagic acid, chebulic acid, catechin, epicatechin, corilagin and epicatechin gallate are the basic aglycones or oligomers of tannin. High temperature reflux extraction can significantly promote the occurrence of the hydrolysis of tannins and significantly increases the content of these components.Therefore, its anti-chronic pharyngitis activity is enhanced. It is suggested that high temperature reflux extraction should be used in the treatment of chronic pharyngitis.

Prognostic value of serum amyloid A in patients with COVID-19.

OBJECTIVE: To investigate the prognostic value of serum amyloid A (SAA) in the patients with Corona Virus Disease 2019 (COVID-19). METHODS: The medical data of 89 COVID-19 patients admitted to Renmin Hospital of Wuhan University from January 3, 2020 to February 26, 2020 were collected. Eighty-nine cases were divided into survival group (53 cases) and non-survival group (36 cases) according to the results of 28-day follow-up. The SAA levels of all patients were recorded and compared on 1 day after admission (before treatment) and 3 days, 5 days, and 7 days after treatment. The ROC curve was drawn to analyze the prognosis of patients with COVID-19 by SAA. RESULTS: The difference of comparison of SAA between survival group and non-survival group before treatment was not statistically significant, Z1 = - 1.426, P = 0.154. The Z1 values (Z1 is the Z value of the rank sum test) of the two groups of patients at 3 days, 5 days, and 7 days after treatment were - 5.569, - 6.967, and - 7.542, respectively. The P values were all less than 0.001, and the difference was statistically significant. The ROC curve results showed that SAA has higher sensitivity to the prognostic value of 1 day (before treatment), 3 days, 5 days, and 7 days after treatment, with values of 0.806, 0.972, 0.861, and 0.961, respectively. Compared with SAA on the 7th day and C-reactive protein, leukocyte count, neutrophil count, lymphocyte count, and hemoglobin on the 7th day, the sensitivities were: 96.1%, 83.3%, 88.3%, 83.3%, 67.9%, and 83.0%, respectively, of which SAA has the highest sensitivity. CONCLUSION: SAA can be used as a predictor of the prognosis in patients with COVID-19.

Clinical features and new diagnostic criteria for the syndrome of periodic fever, aphthous stomatitis, pharyngitis, and cervical adenitis.

AIM: The syndrome of periodic fever, aphthous stomatitis, pharyngitis, and cervical adenitis (PFAPA) is a common inflammatory disease that presents with periodic fever. We aimed to establish more specific diagnostic criteria for PFAPA based on the clinical characteristics of PFAPA patients in our directory. METHOD: The clinical, laboratory, genetic, and family history details of 257 Japanese PFAPA patients treated at our and other affiliated hospitals between April 2000 and April 2018 were analyzed along with quantitative measurements of the number of CD64 molecules on neutrophils, and the levels of serum inflammatory cytokines. The sensitivity and specificity of the criteria were calculated for several diseases. RESULTS: Because recurrent fevers were crucial findings, they were defined as the required criterion. Tonsillitis/pharyngitis with white moss were important accompanying signs. Other symptoms associated with febrile episodes were cervical lymphadenitis with tenderness, aphthous stomatitis, sore throat, vomiting, and headache but not cough. A total of 159 (62%) patients had a family history of recurrent fevers, indicating autosomal dominant inheritance. C-reactive protein levels were extremely elevated during febrile attacks but normal in attack-free periods. Serum immunoglobulin D levels were high in 72 of the 199 tested patients. Oral glucocorticoid and cimetidine were extremely effective in all and 51.6% of the patients, respectively. We defined the above as supportive criteria. These criteria were sensitive and specific enough to distinguish PFAPA from other recurrent fever diseases. Raised serum interferon-γ levels and remarkable CD64 expression on neutrophils during flare-ups were recognized, indicating they contributed to diagnosis. CONCLUSION: Our new criteria are useful for diagnosing PFAPA.

Association of rheumatic fever & rheumatic heart disease with plausible early & late-stage disease markers.

BACKGROUND & OBJECTIVES: Rheumatic fever (RF) and rheumatic heart disease (RHD) are the autoimmune sequelae caused by Group A Streptococcus. RHD still remains a major concern in the developing countries due to its poor diagnosis, lack of vaccines and social awareness among population. This study was aimed to identify the plausible early- and late-stage disease markers associated with RF/RHD. METHODS: A total of 84 patients with confirmed pharyngitis (n=18), RF (n=23) and RHD (n=43) were included in the comparative analysis of different factors involved in host-pathogen interaction during RF/RHD pathogenesis. RESULTS: This study revealed high titre of serum antistreptolysin O (ASO) antibody in pharyngitis compared to RF and RHD patients, whereas procollagen type 1 C-peptide (PICP) level was elevated in RHD which showed an inverse correlation with serum ASO titre. The significant elevation of serum anti-peptide associated with RF (PARF) antibody in RF patients was correlated as a probable stage-specific determinant. In addition, pro-inflammatory cytokine profile revealed high levels of interleukin-12 (IL-12)/IL-23p40, IL-17A in RF, whereas IL-6 concentration was higher in RHD compared to healthy controls. INTERPRETATION & CONCLUSIONS: The overall assessment of the factors/ disease markers involved in host-pathogen interaction in RF/RHD may be suggestive of plausible disease marker in different groups of patients. Further studies with larger sample need to be done to better understand RF/RHD pathogenesis.

Circulating Proteasomes in the Pathogenesis of Head and Neck Squamous Cell Carcinoma.

Increased proteasome activity was revealed in blood serum of patients with stage T1N0M0 head and neck squamous cell carcinoma in comparison with patients with chronic diseases of the larynx and laryngopharynx. This opens prospects of using chymotrypsin-like activity measurement for differential diagnosis of squamous cell carcinoma, screening for high-risk groups, and evaluation of the degree of tumor differentiation.

Could familial Mediterranean fever gene mutations be related to PFAPA syndrome?

BACKGROUND: The cause and pathophysiology of PFAPA syndrome is unknown. The aim of this study was to determine all MEFV gene variants relevant to familial Mediterranean fever in children with PFAPA syndrome. METHODS: All MEFV gene variants were analyzed in patients with PFAPA syndrome. All patients were evaluated using the Gaslini scoring system. Serum immunoglobulin levels were also determined upon admission. RESULTS: We evaluated 64 patients with PFAPA syndrome. The median age at diagnosis was 37.5 (min-max: 6-96) months, and the percentage of male patients was 55.0%. The Gaslini diagnostic score for periodic fever was high in 81.0% of the patients. An MEFV gene mutation was found in 42 (66.0%) children. Mostly, heterozygous or compound heterozygous variants of the MEFV gene were found. Two patients were homozygous for R202Q. MEFV gene mutations were not detected in 22 (34.0%) patients. No significant differences in clinical or laboratory findings were observed between the two groups (p > 0.05), and there were no significant differences in period and duration of the fever episodes (p > 0.05). The fever of all 47 patients (100.0%) who received prednisolone during the episodes decreased within hours and did not recur. Eighteen of the patients using prednisolone underwent prophylaxis with colchicine, and the fever episodes of 9/18 (50.0%) patients using colchicine decreased within months. CONCLUSIONS: Most patients presenting with PFAPA syndrome have heterozygous MEFV gene mutations. Whether carrying a heterozygous MEFV gene is the primary cause of this syndrome requires further investigation.

Association between C-reactive protein rapid test and group A streptococcus infection in acute pharyngitis.

INTRODUCTION: The diagnosis of streptococcal infection is usually made with the use of Centor criteria, but some family doctors also rely on the determination of C-reactive protein (CRP) to guide antibiotic therapy. METHODS: This was an observational study conducted in a health center. Adults with acute pharyngitis and the presence of the 4 Centor criteria (tonsillar exudates, tender cervical glands, history of fever, and absence of cough) were recruited. The patients underwent a pharyngotonsillar swab for microbiologic study and a CRP rapid test during the consultation. RESULTS: A total of 149 patients were enrolled. The most frequent etiology was group A streptococcus, present in 83 cases (55.7%). The highest CRP concentration was observed among patients with group C streptococcus infection, with a mean of 56.3 mg/L (95% confidence interval, 25.7-86.5 mg/L). For patients with group A streptococcus infection, the mean CRP value was 34.4 (95% confidence interval, 25.6-43.3 mg/L). CONCLUSION: CRP concentrations are not associated with group A streptococcus infection in patients with acute pharyngitis. The use of this point of care test is therefore not useful for distinguishing patients who require antibiotic therapy.

Vitamin D levels and effects of vitamin D replacement in children with periodic fever, aphthous stomatitis, pharyngitis, and cervical adenitis (PFAPA) syndrome.

BACKGROUND: The periodic fever, aphthous stomatitis, pharyngitis and cervical adenitis (PFAPA) syndrome is an autoinflammatory disease characterized by regularly recurrent fever episodes due to seemingly unprovoked inflammation. OBJECTIVE: To assess serum 25-hydroxyvitamin D [25(OH)D] concentrations in children with PFAPA syndrome and evaluate longitudinally the effect of wintertime vitamin D supplementation on the disease course. STUDY DESIGN: We have evaluated 25 Italian patients (19 males, 6 females, aged 2.4-5.3 years), fulfilling the Euro-Fever PFAPA criteria. For each patient, we recorded demographic and anthropometric data, clinical manifestations, serum calcium, phosphate, and 25(OH)D. After 400 IU vitamin D supplementation during wintertime, clinical and auxological characteristics, calcium, phosphate, and 25(OH)D levels were re-evaluated. Data were compared with a sex- and age-matched control group. RESULTS: PFAPA patients showed reduced 25(OH)D levels than controls (p<0.0001). Regarding the effect of seasons on vitamin D, winter 25(OH)D levels were significantly reduced than summer ones (p<0.005). Moreover, these levels were significantly lower than in healthy controls (p<0.005), and correlated with both fever episodes (p<0.005) and C-reactive protein values (p<0.005). After vitamin D supplementation, PFAPA patients showed a significantly decreased number of febrile episodes and modification of their characteristics (mean duration of fever episodes, p<0.05; number of febrile episodes per year p<0.005). CONCLUSIONS: Deficient and insufficient vitamin D serum levels were found in most children with PFAPA syndrome, and hypovitaminosis D might be a significant risk factor for PFAPA flares. However, vitamin D supplementation seems to significantly reduce the typical PFAPA episodes and their duration, supporting the role of vitamin D as an immune-regulatory factor in this syndrome.

The mean platelet volume levels in children with PFAPA syndrome.

OBJECTIVES: To assess whether mean platelet volume (MPV) can be used as a marker in the differential diagnosis of periodic fever, aphthous stomatitis, pharyngitis, adenitis (PFAPA) syndrome. METHODS: The leucocyte counts, thrombocyte counts, and MPV values of 57 children with PFAPA syndrome were recorded during an attack and an attack free period. These values were compared with a healthy control group of 55 individuals. Demographic features of the PFAPA patients group including age, gender and age of first attack, age at diagnosis, frequency of attacks, serum reactive protein (CRP) and erythrocyte sedimentation rate (ESR) were also recorded. RESULTS: The MPV values of the children with PFAPA both during an attack and attack free period were found significantly lower than the MPV values of healthy control group (p<0.001). Also, the MPV values of the children with PFAPA during an attack were significantly lower than in attack free periods (p<0.001). The MPV values showed no correlation with leucocytes counts, CRP, and ESR during attacks. A 8.30fl [area under the curve (AUC: 0.965)] optimal cutoff value of MPV with a sensitivity of 89.5% and specificity of 92.8% was determined during an attack in children with PFAPA. CONCLUSIONS: The MPV values during an attack and attack free period of patients with PFAPA is lower than in controls. The MPV values may be used as a marker in the differential diagnosis of PFAPA syndrome but more studies are needed and they should be prospective in order to validate this data.

Periodic fever, aphthous stomatitis, pharyngitis and cervical adenopathy syndrome is associated with activation of GM-CSF and burst-like expression of IL-8 in peripheral blood.

INTRODUCTION: Periodic fever, aphthous stomatitis, pharyngitis and cervical adenopathy (PFAPA) is an autoinflammatory syndrome characterized by periodic fever with aphthous stomatitis, cervical lymphadenopathy, myalgia, and abdominal pain. Peripheral blood concentrations of selected cytokines of PFAPA patients during and between febrile episodes were analyzed in a search for PFAPA-specific molecular signature. METHODS: 23 children with PFAPA (age 6.07 ± 2.94 years, range 5-9 years) and three control children with severe oropharyngeal infections (age 6.2 ± 7.95 years, range 1-17 years) participated in the study. Peripheral blood concentrations of IL-1ß, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, IFN-γ, GM-CSF, TNF-α were measured using Luminex technology. RESULTS: PFAPA febrile episodes were characterized by detection of GM-CSF - 134.07 ± 315.5 pg/mL; significant (P < 0.001), compared to baseline and controls, elevation of concentrations of IL-8 (3193.7 ± 2508 pg/mL vs. 100.36 ± 119. pg/mL vs. 2.04 ± 4.08 pg/mL, respectively), IL-6 (1355.38 ± 2026.53 pg/mL vs. 28.8 ± 44.2 pg/mL and 27.13 ± 26.42 pg/mL, respectively). IL-1ß was detected only in febrile and afebrile PFAPA patients (922.8 ± 1639 pg/mL vs. 10.98 ± 19.4 pg/ml, P < 0.002, respectively), but not in controls. Peripheral blood concentration of TNFα did not differ significantly between study groups. IL-2, IL-4, IL-5, and IL-10 were negligible in all study subjects. DISCUSSION: PFAPA febrile episodes are characterized by activation of GM-CSF and IL-8 with Th1 skewing. We propose a molecular mechanism governing this phenomenon.

Vitamin D linked to PFAPA syndrome.

OBJECTIVE: the etiology and pathogenesis of PFAPA is still unknown, the rapid response to corticosteroids treatment suggested an immune mechanism. The role of vitamin D in the development of immune mediated diseases is widely investigated. In this study we aimed to look for possible association between serum 25-hydroxy vitamin D levels and PFAPA syndrome. METHOD: Twenty-two patients diagnosed with PFAPA followed up at our private clinics between June 2010 and May 2012 were enrolled in the study in addition to 20 patients' age and gender-matched control group. All subjects had complete work-up medical examination and laboratory tests. Laboratory tests included complete blood count, C-reactive protein (CRP), throat culture, and vitamin D levels. RESULTS: mean WBC and CRP values were significantly higher in the PFAPA group (WBC=13.9±2.3×10(3) /mm(2) versus 5.8±3.4×10(3) /mm(2) in the control group (P<0.05) and CRP 37.9±25.7mg/dl versus0.7±1.23mg/dl in the control group (P<0.05)). Vitamin D levels were significantly decreased in PFAPA group as compared with the control (12.27±11.02ng/ml in the PFAPA group versus 20.34±12.64ng/ml in the control group (P<0.05)). Multivariate analysis showed that CRP (odd ratio (OR)=3.0, 95% confidence interval (CI)=2.6-4.2, P=0.01 and serum vitamin D levels <30ng/ml OR=2.6, 95% CI=2.4-3.2, P=0.02 were associated with PFAPA. CONCLUSION: we found a significant correlation between PFAPA and vitamin D deficiency. Vitamin D deficiency can be significant risk factor for PFAPA occurrence.

The association between vitamin D levels and recurrent group A streptococcal tonsillopharyngitis in adults.

OBJECTIVES: To determine the association between recurrent group A streptococcal (GAS) tonsillopharyngitis and serum 25-hydroxy (25(OH)) vitamin D among adult subjects. METHODS: Adult patients with tonsillopharyngitis between January 2007 and December 2009 were reviewed and identified retrospectively. Cases with a medical history of recurrent GAS tonsillopharyngitis were compared to age- and gender-matched individuals without a medical history of GAS tonsillopharyngitis. Recurrent tonsillopharyngitis was defined as three or more episodes of GAS tonsillopharyngitis per year for a period of two consecutive years. RESULTS: Fifty-four cases with recurrent GAS tonsillopharyngitis and 50 controls were enrolled. There were no significant differences between cases and controls with regard to mean age (41 ± 13 vs. 42 ± 12 years; p=0.7) and male gender (55% vs. 54%; p=0.6). Mean serum levels of 25(OH) vitamin D among subjects with recurrent GAS tonsillopharyngitis were significantly lower from the controls (11.5 ng/ml ± 4.7 vs. 26 ng/ml ± 7; p=0.001). Multiple regression analysis showed that a serum 25(OH) vitamin D level <20 ng/ml was associated with recurrent GAS tonsillopharyngitis (odds ratio 1.62, 95% confidence interval 1.51-1.76; p < 0.001). CONCLUSIONS: Our findings indicate a link between vitamin D deficiency and the recurrence of GAS tonsillopharyngitis.

The role of vitamin D in children with recurrent tonsillopharyngitis.

BACKGROUND: The exact etiology of recurrent tonsillopharyngitis in children is not clear. Recurrent tonsillitis in children has multifactorial etiology like most of the diseases in childhood. In this study, our aim was to determine the potential role of vitamin D in recurrent tonsillitis by measuring serum 25-OH vitamin D levels and determining the vitamin D receptor polymorphism among children with recurrent tonsillitis. METHODS: Eighty-four children with recurrent tonsillitis and seventy-one healthy children aging between 2 and 10 years were enrolled in this study. Serum 25-OH vitamin D level was measured with ELISA and vitamin D receptor gene polymorphism (Apa1, Taq 1, Fok1) was determined by PCR. Serum 25-OH vitamin D level below 50 nmol/L was accepted as deficiency. The vitamin D receptor gene polymorphism in each group was compared. RESULTS: The mean age was 5.6 ± 2.4 and 6.1 ± 2.7 years in study and control group, respectively. The average serum 25-OH vitamin D level was 142.7 ± 68.1 nmol/L in study group and 192.3 ± 56.1 nmol/L in control group. There was significant difference between the groups (p < 0.01). In study group, 4.7% (n = 4) of children had serum 25 OH vitamin D levels below 50 nmol/L. None of the children in control group had serum 25-OH vitamin D level below 50 nmol/L. There was no significant differences in vitamin D receptor gene polymorphisms between groups. CONCLUSION: Serum 25-OH vitamin D levels in recurrent tonsillitis group were lower than those in healthy children. But, there was no difference in the incidence of vitamin D receptor gene polymorphism between the two groups.

C-reactive protein and procalcitonin during febril attacks in PFAPA syndrome.

OBJECTIVES: To assess the levels of procalcitonin (PCT) and C-reactive protein (CRP) in children diagnosed with PFAPA (periodic fever, aphthous stomatitis, pharyngitis, and cervical adenitis) during their febrile attacks. METHODS: 23 patients with diagnosis of PFAPA included into the study prospectively during a three years period. In these patients, CRP and PCT values were recorded during 78 febrile episodes. Furthermore, 20 patients with diagnosis of pneumonia were chosen as a control group and their CRP and PCT values were measured. Normal reference values for CRP and PCT were 0-10 mg/L and 0-0.5 ng/mL, respectively. RESULTS: Mean CRP and PCT values of patients with PFAPA were 94.8±71.6 mg/L and 0.29±0.14 ng/mL, respectively. In control group, mean CRP value was 153.2±26 mg/L and PCT was 1.59±0.53 ng/mL. CRP and PCT were high in control group. CRP was detected high and PCT was normal in PFAPA. Compared to control group, in PFAPA group, CRP values were not significantly (p>0.05) and PCT values were significantly lower (p<0.001). CONCLUSION: During febrile episodes in the patients with diagnosis of PFAPA, CRP values were substantially elevated, whereas PCT values were within normal levels. Concomitant assessment of CRP and PCT in addition to clinical diagnostic criteria may be of help in making diagnosis and distinguishing febrile attacks from infections. However, studies in larger groups are required.

Multi high-throughput approach for highly selective identification of vaccine candidates: the Group A Streptococcus case.

We propose an experimental strategy for highly accurate selection of candidates for bacterial vaccines without using in vitro and/or in vivo protection assays. Starting from the observation that efficacious vaccines are constituted by conserved, surface-associated and/or secreted components, the strategy contemplates the parallel application of three high throughput technologies, i.e. mass spectrometry-based proteomics, protein array, and flow-cytometry analysis, to identify this category of proteins, and is based on the assumption that the antigens identified by all three technologies are the protective ones. When we tested this strategy for Group A Streptococcus, we selected a total of 40 proteins, of which only six identified by all three approaches. When the 40 proteins were tested in a mouse model, only six were found to be protective and five of these belonged to the group of antigens in common to the three technologies. Finally, a combination of three protective antigens conferred broad protection against a panel of four different Group A Streptococcus strains. This approach may find general application as an accelerated and highly accurate path to bacterial vaccine discovery.

Alterations in the expression of translation factors as molecular markers in cadmium-exposed workers.

Eukaryotic translation initiation factor 3 (eIF3) and elongation factor 1δ (eEF-1δ) are novel cadmium (Cd) responsive proto-oncogenes. This research investigated the expression of these genes in Cd-exposed workers (n = 58), and to evaluate their usefulness as biomarkers of Cd exposure. According to urinary Cd concentration, the subjects were divided into four groups (urinary Cd concentration ≥0.1 µg/g.Cr, ≥1.0 µg/g.Cr, ≥5.0 µg/g.Cr and ≥50.0 µg/g.Cr). Subjects exhibited increased severe health problems with higher urinary Cd concentrations. The eIF3 and eEF-1δ expression in the blood were investigated with real-time PCR. PCR data showed a strong positive correlation between blood eEF-1δ and urinary Cd concentrations (r = 0.788, p < 0.01), and a weak positive correlation between blood eIF3 expression and urinary Cd concentrations (r = 0.569, p < 0.05). These findings, for the first time, demonstrate that the blood eEF-1δ overexpression can be used as a molecular biomarker of Cd-exposed population.

Experimental investigation of the immunoregulatory and anti-inflammatory effects of the traditional Chinese medicine "Li-Yan Zhi-Ke Granule" for relieving chronic pharyngitis in rats.

Chronic pharyngitis, a chronic inflammation of the pharyngeal mucous membrane and submucous lymphoid tissues, is often caused by unsatisfactory treatment of acute pharyngitis or repeated occurrences of upper respiratory tract infection and is related to a high-dust environment. Traditional herbal pharmacotherapy is well known for combining plant species to create complex phytochemical mixtures in the attempt to ameliorate pathophysiological processes. The aim of current study is to investigate the effect of immunoregulation and anti-inflammation with the traditional Chinese medicine (TCM) "Li-Yan Zhi-Ke Granule" in rats. Determination of serum hemolysin and the carbon particle clearance test were performed. The results demonstrate that administration of the TCM "Li-Yan Zhi-Ke Granule" may improve the effect of phagocytosis by mononuclear macrophages and immune function in rats, and may also increase the immunoregulatory and anti-inflammatory responses of rats with chronic pharyngitis. This traditional drug could relieve the symptoms of sore throat and cough in rats with chronic pharyngitis.