Effects of vitamin D supplementation on the bone specific biomarkers in HIV infected individuals under treatment with efavirenz

ABSTRACT: BACKGROUND: It was reported that antiretroviral drugs such as efavirenz can increase the catabolism of vitamin D in HIV infected individuals. We have not found any study that evaluated effects of vitamin D supplementation on the bone specific biomarkers in HIV positive patients under treatment with antiretroviral regimen containing efavirenz. FINDINGS: Vitamin D deficiency was detected in 88.4 % of included patients. Baseline osteocalcin, but not collagen telopeptidase, serum levels were lower than normal range in all of these individuals. Both bone biomarkers' concentrations increased significantly (p < 0.001 for both of them) after supplementation of vitamin D and it was more predominant for osteocalcin. CONCLUSION: In the HIV-infected patients under treatment with efavirenz, vitamin D deficiency is prevalent. After supplementation with single dose of 300,000 IU vitamin D in this population, the activation of osteoblasts and osteoclasts stimulates bone formation and resorption respectively with favorable bone formation without any adverse event. Significant percent of HIV infected individuals are vitamin d deficient that could benefit from vitamin D supplementation.     

Diabetic neuropathy and axon reflex-mediated neurogenic vasodilatation in type 1 diabetes

Objective

Axon reflex-mediated neurogenic vasodilatation in response to cutaneous heating may reflect early, pre-clinical small fibre dysfunction. We aimed to evaluate the distribution of the vascular flare area measured by laser doppler imaging (“LDI_FLARE area”) in type 1 diabetes and in healthy volunteers.

Research and Methods

Concurrent with clinical and electrophysiological examination to classify diabetic sensorimotor polyneuropathy (DSP), LDI_FLARE area (cm²) was determined in 89 type 1 diabetes subjects matched to 64 healthy volunteers. We examined the association and diagnostic performance of LDI with clinical and subclinical measures of DSP and its severity.

Results

Compared to the 64 healthy volunteers, the 56 diabetes controls without DSP had significantly lower LDI_FLARE area (p = 0.006). The 33 diabetes cases with DSP had substantially lower LDI_FLARE area as compared to controls without DSP (p = 0.002). There was considerable overlap in LDI_FLARE area between all groups such that the ROC curve had an AUC of 0.72 and optimal sensitivity of 70% for the detection of clinical DSP. Use of a subclinical definition for DSP, according to subclinical sural nerve impairment, was associated with improved AUC of 0.75 and sensitivity of 79%. In multivariate analysis higher HbA1c and body mass index had independent associations with smaller LDI_FLARE area.

Conclusions

Axon reflex-mediated neurogenic vasodilatation in response to cutaneous heating is a biomarker of early nerve dysfunction in DSP. Its independent association with glycemic exposure in diabetes subjects and both glycemic exposure and BMI in healthy volunteers highlights the existence of small-fibre dysfunction in the natural history of DSP.     

Natural Killer Cell Signal Integration Balances Synapse Symmetry and Migration

Natural killer (NK) cells discern the health of other cells by recognising the balance of activating and inhibitory ligands expressed by each target cell. However, how the integration of activating and inhibitory signals relates to formation of the NK cell immune synapse remains a central question in our understanding of NK cell recognition. Here we report that ligation of LFA-1 on NK cells induced asymmetrical cell spreading and migration. In contrast, ligation of the activating receptor NKG2D induced symmetrical spreading of ruffled lamellipodia encompassing a dynamic ring of f-actin, concurrent with polarization towards a target cell and a “stop” signal. Ligation of both LFA-1 and NKG2D together resulted in symmetrical spreading but co-ligation of inhibitory receptors reverted NK cells to an asymmetrical migratory configuration leading to inhibitory synapses being smaller and more rapidly disassembled. Using micropatterned activating and inhibitory ligands, signals were found to be continuously and locally integrated during spreading. Together, these data demonstrate that NK cells spread to form large, stable, symmetrical synapses if activating signals dominate, whereas asymmetrical migratory “kinapses” are favoured if inhibitory signals dominate. This clarifies how the integration of activating and inhibitory receptor signals is translated to an appropriate NK cell response.     

Serum Zinc and Copper Levels in Ischemic Cardiomyopathy

Changes in the copper (Cu) and zinc (Zn) concentrations have been reported previously in ischemic cardiomyopathy (ISCMP). Due to controversial results, the aims of this study were to compare levels of Cu, Zn, and Zn/Cu ratio of ISCMP patients with healthy volunteers and also to investigate the possible relationship between trace elements status in ISCMP patients with the severity of clinical disease based on the New York Heart Association (NYHA) classification. The subjects of this study consisted of 30 ISCMP and 27 healthy volunteers. ISCMP was diagnosed with a history of previous myocardial infarction and also coronary artery disease was confirmed by coronary angiography. Exclusion criteria were renal or hepatic insufficiency, alcohol usage, and intake of supplements containing Cu or Zn within 1 week. Cu and Zn levels have been assayed with atomic absorption spectrophotometry. Statistical analysis was performed with the SPSS 10 software using independent sample t test for comparing the levels of Cu and Zn between ISCMP and normal subjects. The mean Cu level of the ISCMP group (1.54 ± 0.52 mg/L) was significantly more than the Cu levels of the healthy volunteers (1.31 ± 0.24 mg/L; p = 0.048). The mean Zn levels of the ISCMP and healthy volunteers were 1.05 ± 0.28 and 1.12 ± 0.42, respectively, without any significant difference between groups. There was a trend for higher Cu level, lower Zn level, and lower Zn/Cu ratio in NYHA III patients in comparison with NYHA II group. Considering the results of this study, Cu may have a role in the development of ISCMP. Interventions such as administration of Cu chelators to relieve the symptoms or to decrease the progression of ISCMP is needed to be examined in large clinical trials. In this study, the Zn level of ISCMP patients was not significantly different in comparison with the healthy volunteers.     

Biotransformation of monoterpenes by Oocystis pusilla

The biotransformation of several monoterpenes by the locally isolated unicellular microalga, Oocystis pusilla was investigated. The metabolites were identified by thin layer chromatography and GC/MS. The results showed that O. pusilla had the ability to reduce the C=C double bond in (+)-carvone to yield trans-dihydrocarvone and traces of cis-dihydrocarvone. O. pusilla also converted (+)-limonene to trans-carveol, as the main product, and yielded carvone and trans-limonene oxide. Furthermore, (−)-linalool was converted to trans-furanoid and trans-pyranoid linalool oxide, thymol was converted to thymoquinone, (−)-carveol was converted to carvone and trans-dihydrocarvone, (−)-menthone and (+)-pulegone were converted to menthol, (L)-citronellal was converted to citronellol, and (+)-β-pinene was converted to trans-pinocarveol.     

In the trenches of plant pathogen recognition: Role of NB-LRR proteins

As in nearly every discipline of plant biology, new insights are constantly changing our understanding of plant immunity. It is now clear that plant immunity is controlled by two layers of inducible responses: basal responses triggered by conserved microbial features and specific responses triggered by gene-for-gene recognition of pathogen effector proteins by host resistance (R) proteins. The nucleotide-binding domain leucine-rich repeat (NB-LRR) class of R proteins plays a major role in the combat against a wide range of plant pathogens. The variation that has been generated and is maintained within these conserved proteins has diversified their specificity, subcellular localisations, activation and recognition mechanisms, allowing them to specifically adapt to different plant–pathogen interaction systems. This review addresses recent advances in the molecular role of NB-LRR proteins in pathogen recognition and activation of plant defence responses.     

The effect of acute high light and low temperature stresses on the ascorbate–glutathione cycle and superoxide dismutase activity in two Dunaliella salina strains

Dunaliella species accumulate carotenoids and their role in protection against photooxidative stress has been investigated extensively. By contrast, the role of other antioxidants in this alga, has received less attention. Therefore, the components of the ascorbate–glutathione cycle, along with superoxide dismutase (E.C. 1.15.1.1) and peroxidase (E.C. 1.11.1.11) activity were compared in two strains of Dunaliella salina. Strain IR‐1 had two‐fold higher chlorophyll and β‐carotene concentration than Gh‐U. IR‐1 had around four‐fold higher superoxide dismutase, ascorbate peroxidase and pyrogallol peroxidase activities than Gh‐U on a protein basis. Ascorbate and glutathione concentrations and redox state did not differ between strains and there was little difference in the activity of ascorbate–glutathione cycle enzymes (monodehydroascorbate reductase [E.C. 1.6.5.4], dehydroascorbate reductase [E.C. 1.8.5.1] and glutathione reductase [E.C. 1.8.1.7]). The response of these antioxidants to high light and low temperature was assessed by transferring cells from normal growth conditions (28°C, photon flux density of 100 μmol m^?2 s^?1)to 28°C/1200 μmol m^?2 s^?1; 13°C/100 μmol m^?2 s^?1; 13°C/1200 μmol m^?2 s^?1 and 28°C/100 μmol m^?2 s^?1 for 24 h. Low temperature and combined high light‐low temperature decreased chlorophyll and β‐carotene in both strains indicating that these treatments cause photooxidative stress. High light, low temperature and combined high light‐low temperature treatments increased the total ascorbate pool by 10–50% and the total glutathione pool by 20–100% with no consistent effect on their redox state. Activities of ascorbate–glutathione cycle enzymes were not greatly affected but all the treatments increased superoxide dismutase activity. It is concluded that D. salina can partially adjust to photooxidative conditions by increasing superoxide dismutase activity, ascorbate and glutathione.