The effect of diabetes mellitus on immunological response to hepatitis B virus vaccine in individuals with chronic kidney disease: A meta-analysis of current literature

Background

Patients with chronic kidney disease (CKD) often fail to produce protective antibodies to hepatitis B virus (HBV) surface antigen after vaccination. Diabetes mellitus (DM) is the most common cause of CKD; however it is not clear whether it affects immunological response to HBV vaccine in these patients.

Aims

We aimed to evaluate the immunological response to HBV vaccine in diabetic patients with CKD by conducting a meta-analysis of the current literature.

Methods

Only studies that evaluated the seroprotection rate for diabetic against non-diabetic CKD patients or the immunological response of these groups to HBV vaccine were included. We applied the random effects model of DerSimonian and Laird, with heterogeneity (Q statistic), publication bias (Egger and Begg test) and sensitivity analyses. The rate of patients showing seroprotective anti-HBsAg titers (>10 IU/mL) at completion of HBV vaccination schedule in the diabetic versus the non-diabetic CKD patients was set as our end-point of interest.

Results

We identified seven studies that fulfilled our inclusion criteria involving 15,073 unique patients with CKD. Aggregation of study results showed a significant decrease in response rates among the diabetic versus the non-diabetic patients [pooled odds ratio = 0.58 (95% CI 0.37–0.89), Q(6) = 11.3, I² = 50%]. The P-value was 0.07 for our test of heterogeneity.

Conclusions

Our meta-analysis determined that HBV vaccination's seroprotection rate in diabetic CKD patients is significantly lower than that in non-diabetic CKD patients. Therefore, using vaccine adjuvants such as oral levamisole, granulocyte macrophage-colony stimulating factor or intradermal injection might be advisable in these patients.     

Soy,Soy Isoflavones,and Protein Intake in Relation to Mortality from All Causes,Cancers, and Cardiovascular Diseases: A Systematic Review and Dose–Response Meta-Analysis of Prospective Cohort Studies

ObjectiveWe conducted a systematic review and dose–response meta-analysis of prospective studies to summarize findings on the associations between intakes of soy, soy isoflavones, and soy protein and risk of mortality from all causes, cancers, and cardiovascular diseases.MethodsOnline databases were systematically searched to identify relevant articles published earlier than May 2018. We applied restricted cubic splines using random-effects analysis to assess dose–response associations. Between-study heterogeneity was assessed by I² value and Cochrane Q test. Potential publication bias was assessed by visual inspection of funnel plots and Begg regression test.ResultsIn total, 23 prospective studies with an overall sample size of 330,826 participants were included in the current systematic review and the meta-analysis. Soy/soy products consumption was inversely associated with deaths from cancers (pooled relative risk 0.88, 95% CI 0.79 to 0.99; P=0.03; I²=47.1%, 95% CI 0.0% to 75.4%) and cardiovascular diseases (pooled effect size: 0.85, 95% CI 0.72 to 0.99; P=0.04; I²=50.0%, 95% CI 0.0% to 77.6%). Such significant associations were also observed for all-cause mortality in some subgroups of the included studies, particularly those with higher quality. In addition, higher intake of soy was associated with decreased risk of mortality from gastric, colorectal, and lung cancers as well as ischemic cardiovascular diseases. Participants in the highest category of dietary soy isoflavones intake had a 10% lower risk of all-cause mortality compared with those in the lowest category. We also found that a 10-mg/day increase in intake of soy isoflavones was associated with 7% and 9% decreased risk of mortality from all cancers and also breast cancer respectively. Furthermore, a 12% reduction in breast cancer death was indicated for each 5-g/day increase in consumption of soy protein. However, intake of soy protein was not significantly associated with all-cause and cardiovascular diseases mortality.ConclusionsSoy and its isoflavones may favorably influence risk of mortality. In addition, soy protein intake was associated with a decreased risk in the mortality of breast cancer. Our findings may support the current recommendations to increase intake of soy for greater longevity.     

Purification and characterization of α-amylase in Moroccan locust,Dociostaurus maroccanus Thunberg (Orthoptera: Acrididae) and its inhibition by inhibitors from Phaseolus vulgaris L.

An α-amylase with molecular weight of 73?kDa was purified from midgut of Dociostaurus maroccanus using ammonium sulfate precipitation, gel filtration, and ion exchange chromatography. The optimal pH and temperature were 6 and 45?°C, respectively. As calculated using Lineweaver–Burk plots, the Km was about 0.62?mM and the Vmax was 1.113 (μmol/min/mg protein). Mn²⁺, Hg⁺, Zn²⁺ and ethylene diamine tetraacetic acid (EDTA) decreased α-amylase activity of D. maroccanus, whereas the addition of K⁺, Na⁺, Fe²⁺, Ba⁺, Mg²⁺, Ca²⁺ and Co²⁺ increased enzyme activity. Alpha-amylase inhibitors (AI1, AI2) with molecular weights of 43?kDa and 29?kDa, respectively, were purified from the seeds of Phaseolus vulgaris and its inhibitory effect on purified α-amylase of D. maroccanus was investigated. These inhibitors inhibited the D. maroccanus gut α-amylase activity significantly.     

Protective role of simvastatin on isolated rabbit atrioventricular node during experimental atrial fibrillation model: role in rate control of ventricular beats

The purpose of the present study was to determine (1) whether simvastatin (SV) modifies the rate-dependent conduction time and refractoriness of the atrioventricular (AV) node and (2) how it can change the protective mechanism of the AV node during atrial fibrillation (AF). Predefined stimulation protocols were applied to detect the electrophysiological parameters of the AV node, including atrial-His conduction time, effective refractory period (ERP), functional refractory period (FRP), concealed conduction, excitable index, and fatigue in two groups of isolated, perfused rabbit AV nodal preparations (N=16). The stimulation protocols (fatigue, recovery) were carried out during control and in the presence of SV (0.5, 0.8, 3, and 10 μM). Simulated AF was executed in a separate group (N=8), and specific indexes, including H-H mean, zone of concealment (ZOC), and concealed beats were recorded. SV, in a concentration-dependent manner, prolonged ERP, FRP, and Wenckebach cycle lengths. It (10 μM) significantly increased fatigue and the excitable index. In addition, SV elicited prolongation of ZOC and H-H mean at 3 and 10 μM. SV-evoked prolongation of nodal refractoriness and concealed conduction caused rate-dependent ventricular slowing effects during AF. The ability of simvastatin to decrease the excitable gap by its heterogeneous effects on nodal dual pathways proposes its protective role in AF.     

Assessment of Cadmium,Copper, Lead and Zinc Contamination Using Oysters (<Emphasis Type="Italic">Saccostrea cucullata</Emphasis>) as Biomonitors on the Coast of the Persian Gulf,Iran

The levels of Cd, Cu, Pb and Zn in surface sediment, soft tissue and shell of the oyster Saccostrea cucullata collected from three locations, in the intertidal zones of Lengeh Port, northern part of Persian Gulf were measured. Results indicated that there were a positive correlation across Zn (r = 0.58, p = 0.025), Cd (r = 0.74, p < 0.01) and Cu (r = 0.80, p < 0.01) levels in the soft tissue of oyster and sediment which supported this fact that the soft tissue of S. cucullata can be considered as biomonitoring agent for Cd, Zn and Cu in the Lengeh Port.     

Liposomal SLA co-incorporated with PO CpG ODNs or PS CpG ODNs induce the same protection against the murine model of leishmaniasis

First generation Leishmania vaccines consisting of whole killed parasites with or without adjuvants have reached phase 3 trial and failed to show enough efficacy mainly due to the lack of an appropriate adjuvant. In this study, the nuclease-resistant phosphorothioate CpG oligodeoxynucleotides (PS CpG) or nuclease-sensitive phosphodiester CpG ODNs (PO CpG) were used as adjuvants to enhance immunogenicity and rate of protection against leishmaniasis. Due to the susceptibility of PO CpG to nuclease degradation, an efficient liposomal delivery system was developed to protect them from degradation. 1, 2-dioleoyl-3-trimethylammonium-propane (DOTAP) as a cationic lipid was used because of its unique adjuvanticity and electrostatic interaction with negatively charged CpG ODNs. To evaluate the role of liposomal formulation in protection rate and enhanced immune response, BALB/c mice were immunized subcutaneously with liposomal soluble Leishmania antigens (SLA) co-incorporated with PO CpG (Lip-SLA-PO CpG), Lip-SLA-PS CpG, SLA+PO CpG, SLA+PS CpG, SLA or buffer. As criteria for protection, footpad swelling at the site of challenge, parasite loads, the levels of IFN-γ and IL-4, and the IgG subtypes were evaluated. The groups of mice receiving Lip-SLA-PO CpG or Lip-SLA-PS CpG showed a high protection rate compared with the control groups. In addition, there was no significant difference in immune response generation between mice immunized with PS CpG and the group receiving PO CpG when incorporated into the liposomes. The results suggested that liposomal form of PO CpG might be used instead of PS CpG in future vaccine formulations as an efficient adjuvant.     

Determination of trace elements in patients with chronic hepatitis B

Chronic hepatitis B virus (HBV) infection is a major liver disease worldwide and its clinical manifestations are linked to immune response. The purpose of this study was to evaluate the relationship between selenium, copper, and zinc in comparison with transaminase level in chronic HBV patients. Serum samples of the HBV infected patients were obtained from Tooba medical center, Sari, Iran. Sixty patients were enrolled in this study (36 men and 24 women), mean age: 39.6 ± 12.2 years. The concentration of zinc, selenium, copper and transaminases were determined using an autoanalyzer system. Concentrations of selenium (0.273 ± 0.056 μg/dl) and zinc (2.1 ± 0.037) was elevated in patients with low transaminase levels as were significantly different in comparison with patients with high transaminase level (P<0.05). Serum copper concentration was similar in two groups of patients. Elevated levels of transaminase concentrations were independently associated with low zinc and selenium concentrations in chronic HBV patients. It is concluded that serum zinc and selenium levels are associated with less hepatic damage in chronic HBV patients and might have a protective role during liver injury.     

Distribution of the anterior,posterior, and total corneal astigmatism in healthy eyes

Purpose

To evaluate the magnitude and axis orientation of the anterior, posterior, and total corneal astigmatism in normal healthy eyes of an Iranian population.

Methods

In a prospective cross-sectional study, ophthalmic and anterior segment parameters of 153 healthy eyes of 153 subjects were evaluated by Galilei dual Scheimpflug analyzer. The magnitude and axis orientation [with-the-rule (WTR), against-the-rule (ATR), and oblique] of the anterior, posterior, and total corneal astigmatism measurements (ACA, PCA, and TCA) were compared according to the age, sex, and other ophthalmic parameters.

Results

The mean ± SD age of the study population was 30 ± 5.9 years. The mean magnitude was 1.09 ± 0.76 diopters (D) for ACA, 0.30 ± 0.13 D for PCA, and 1.08 ± 0.77 D for TCA. Males had a significantly higher magnitude of PCA than females (p = 0.041). Most eyes had a WTR anterior astigmatism and an ATR posterior astigmatism. The WTR astigmatism had a higher mean magnitude compared to the ATR and oblique astigmatism in all the astigmatism groups, with a significant difference in the ACA and TCA groups (p < 0.05). PCA magnitude exceeded 0.50 D in only 7.8% of the subjects. ACA, PCA, and TCA were significantly correlated with each other and also had a significant correlation with the anterior and posterior maximum corneal elevation measurements (p < 0.001).

Conclusion

The results of this study although are limited due to the small number of participants and confined to our demographics, provided information regarding a population that was not described before and may be helpful in obtaining optimum results in astigmatism correction in refractive surgery or designing new intraocular lenses.

     

Olive (Olea europaea L.) leaf extract attenuates early diabetic neuropathic pain through prevention of high glucose-induced apoptosis: in vitro and in vivo studies

Aim of study

Since the leaves of olive have been recommended in the literature as a remedy for the treatment of diabetes and they also contain antioxidant agents, we decided to investigate the possible effects of olive leaf extract (OLE) on in vitro and in vivo models of diabetic pain neuropathy.

Materials and methods

The high glucose-induced cell damage in naive and NGF-treated Pheochromocytoma (PC12) cells and streptozotocin-induced diabetic rats were used. Tail-flick test was used to access nociceptive threshold. Cell viability was determined by MTT assay. Biochemical markers of neural apoptosis were evaluated using immunoblotting.

Results

We found that elevation of glucose (4 times of normal) sequentially increases functional cell damage and caspase-3 activation in NGF-treated PC12 cells. Incubation of cells with OLE (200, 400 and 600 μg/ml) decreased cell damage. Furthermore, the diabetic rats developed neuropathic pain which was evident from decreased tail-flick latency (thermal hyperalgesia). Activated caspase 3 and Bax/Bcl2 ratio were significantly increased in spinal cord of diabetic animals. OLE treatment (300 and 500 mg/kg per day) ameliorated hyperalgesia, inhibited caspase 3 activation and decreased Bax/Bcl2 ratio. Furthermore, OLE exhibited potent DPPH free radical scavenging capacity.

Conclusion

The results suggest that olive leaf extract inhibits high glucose-induced neural damage and suppresses diabetes-induced thermal hyperalgesia. The mechanisms of these effects may be due, at least in part, to reduce neuronal apoptosis and suggest therapeutic potential of olive leaf extract in attenuation of diabetic neuropathic pain.     

Radioprotective Effect of Achillea millefolium L Against Genotoxicity Induced by Ionizing Radiation in Human Normal Lymphocytes

The radioprotective effect of Achillea millefolium L (ACM) extract was investigated against genotoxicity induced by ionizing radiation (IR) in human lymphocytes. Peripheral blood samples were collected from human volunteers and incubated with the methanolic extract of ACM at different concentrations (10, 50, 100, and 200 μg/mL) for 2 hours. At each dose point, the whole blood was exposed in vitro to 2.5 Gy of X-ray and then the lymphocytes were cultured with mitogenic stimulation to determine the micronuclei in cytokinesis-blocked binucleated cell. Antioxidant capacity of the extract was determined using free radical-scavenging method. The treatment of lymphocytes with the extract showed a significant decrease in the incidence of micronuclei binucleated cells, as compared with similarly irradiated lymphocytes without any extract treatment. The maximum protection and decrease in frequency of micronuclei were observed at 200 μg/mL of ACM extract which completely protected genotoxicity induced by IR in human lymphocytes. Achillea millefolium extract exhibited concentration-dependent radical-scavenging activity on 1,1-diphenyl-2-picryl hydrazyl free radicals. These data suggest that the methanolic extract of ACM may play an important role in the protection of normal tissues against genetic damage induced by IR.