DNA interaction,anti-proliferative effect of copper oxide nanocolloids prepared from metallosurfactant based microemulsions acting as precursor,template and reducing agent

In the present study, we have synthesized mixed cuprous/copper oxide nanosuspensions by metallosurfactant based microemulsion technique. Three metallosurfactants were synthesized which includes two non-ionic double chained metallosurfactants with C₁₂, C₁₆ chains with coordinated copper i.e. Cudda and Cuhexa, respectively. Another cationic double chained metallosurfactant with loosely bound metal (Cuctac) was also prepared. The prepared metallocomplexes were characterized using FTIR, elemental analysis, and NMR. The effect of the position of metallosurfactant in microemulsion on the fabrication and properties of nanosuspensions was elucidated. In this method, no external reducing agent and capping agent were added and tween 80 acted both as reducing and stabilizing agent for the nanoparticles. The synthesized nanoparticles were characterized and it was observed that mixed copper and cuprous oxide particles are present in colloidal suspension for all the three studied metallosurfactants. The kinetics of formation of mixed copper/cuprous oxide nanosuspensions (Ns) and their stability was estimated using Uv-visible spectroscopy. Further, the binding and interactions of copper nanosuspensions with calf Thymus DNA (CT-DNA) were assessed using Uv–vis spectroscopy, circular dichroism and gel electrophoresis. Additionally, the antioxidant activity of the Cu Ns was checked using DPPH assay. The role of positive charge on nanoparticles as evaluated from Zeta potential was responsible for DNA affinity. The DNA conformational changes in the presence of nanosuspensions and relevant scavengers were investigated. Further, the anti-proliferative activity of copper Ns was assessed using HeLa cells and Cuhexa derived Ns were proved to be active with highest activity at a low concentration and were nontoxic towards normal cell lines. In summary, this work demonstrates a softer approach for the synthesis of copper nanosuspensions with a size range of 2–5?nm and evaluated the role of type and structure of metallosurfactant on size, stability of particles and anti-proliferative activity.     

Itolizumab,a novel anti-CD6 monoclonal antibody: a safe and efficacious biologic agent for management of psoriasis

Introduction: Psoriasis, a chronic immune-mediated skin disorder is associated with significant physical, psychological, and quality of life impairments. Along with well-documented genetic and environmental factors, immunological factors also contribute to the pathogenesis of psoriasis. Among the immunological factors, CD6 – dependent T-cell proliferation to form Th1 and Th17 cells play a major role in the pathogenesis of psoriasis. Itolizumab is the first humanized IgG1 monoclonal antibody, which selectively targets CD6.

Areas covered: The current article presents the pharmacology of itolizumab and provides a review of the currently available data on the efficacy and safety of itolizumab for management of moderate to severe plaque psoriasis.

Expert opinion: The use of biologics to attenuate the immune-mediated pathological events in psoriasis is a relatively well-established clinical practice. However, the safety and efficacy of biologics continues to be an unsettled topic of ongoing research. While available data seems to suggest that itolizumab may be a safer option, additional studies with higher sample sizes and active comparators are needed before definitive conclusions can be drawn on the place of itolizumab in the management of psoriasis.     

Peripheral vascular disease: who gets it and why? A histomorphological analysis of 261 arterial segments from 58 cases

AIMS: This retrospective study aimed to document and illustrate the histomorphological changes underlying peripheral vascular disease (PVD). More specifically, it aimed to analyse and quantify those changes that lead to lower limb amputations. Histological changes were assessed in relation to various clinical pathologies, and significant correlations were sought thereafter. METHODS: A total of 1305 arterial segments were examined from 58 consecutive patients undergoing a lower limb amputation from January 2002 to December 2003. Serial arterial segments were taken from the femoral, popliteal, anterior tibial, posterior tibial, peroneal, and dorsalis pedis arteries, and the degrees of atherosclerotic stenosis and medial calcification were histologically quantified. RESULTS: Atherosclerosis was associated with severe arterial stenosis. An increased occurrence of severe atherosclerotic narrowing coincided with increasing patient age (p = 0.0166), hypertension (p = 0.0019), and diabetes mellitus (p = 0.0036). The presence of medial calcification was an important pathological feature in patients under 70 years of age (p = 0.0308) and significantly more severe in those with diabetes mellitus (p<0.001). CONCLUSION: Atherosclerosis and medial calcification are significant underlying lesions in diabetic patients undergoing lower limb amputation. Medial calcification can cause significant stiffening of the arterial wall and a reduction in its ability to respond to vasodilator stimuli.     

Association of MIF gene polymorphisms with pemphigus vulgaris: a case-control study with comprehensive review of the literature

Background: Functional macrophage migration inhibitory factor (MIF) gene polymorphisms are associated with elevated serum levels of MIF and increased susceptibility to various autoimmune diseases. MIF levels in the sera of pemphigus vulgaris (PV) patients are increased; however, no definite association has been demonstrated between PV and MIF gene polymorphisms. The present study was conducted to ascertain any association between MIF-173*G-C and MIF-794*CATT_5-8 polymorphisms and PV. Methods: Seventy-five patients with PV and 252 healthy, unrelated, voluntary controls were enrolled randomly in the study. MIF-173*G-C polymorphism (rs755622) was genotyped using polymerase chain reaction (PCR) followed by restriction fragment length analysis, and MIF-794*CATT_5-8 (rs5844572) was genotyped using PCR followed by capillary gel electrophoresis. Subsequently, the allelic, genotype, and haplotype frequencies were determined and compared for both groups. Data were also analyzed with respect to sex, age at onset, type of disease, and duration of disease. Results: No significant association was observed in terms of allelic, genotype, and haplotype frequencies of MIF gene polymorphisms in PV patients. However, a significantly lower prevalence of the C allele (P=0.02) and CATT₇ allele (P=0.03) was seen in our patient population compared to healthy controls. Analysis of the effect of various factors such as gender, age at onset, type of disease, and disease duration revealed no significant association with the genetic variants. Conclusions: MIF-173*G-C and -794*CATT_5-8 polymorphisms are not associated with PV.     

Tyrosine kinase B protein expression is reduced in the cerebellum of patients with bipolar disorder

Background

The role of the cerebellum in coordinating mental activity is supported by its connections with cerebral regions involved in cognitive/affective functioning, with decreased activities on functional neuroimaging observed in the cerebellum of schizophrenia patients performing mental tasks. Brain-derived neurotrophic factor (BDNF)-induced activation of tyrosine kinase B (TrkB) is essential to synaptic plasticity. We hypothesized that alterations in BDNF and TrkB expression in the cerebellum were associated with schizophrenia and affective disorders.

Methods

We employed immunohistochemistry and immunoblotting to quantify protein expression of BDNF and TrkB in the cerebellum of patients with schizophrenia, bipolar disorder, and major depression compared to controls (n = 15 each).

Results

While TrkB immunoreactivity in each of the molecular and granule-cell layers was reduced in all 3 disease groups (12-34%) compared to the control (P = 0.018 and 0.038, respectively, ANOVA), only the reduction in bipolar disorder remained statistically significant upon Tukey-Kramer post hoc analyses (P = 0.019 and 0.021, respectively). Apparent decreases in BDNF immunoreactivity in all 3 disease groups (12-30%) compared to the control were not statistically significant. TrkB immunoreactivity was not significantly associated with any of the demographic, clinical, and postmortem variables. Immunoblotting displayed an 85-kDa TrkB-immunoreactive band, consistent with a truncated isoform, in all 60 cases.

Limitations

On immunoblotting, apparent decreases in 85-kDa-TrkB levels in all 3 disease groups compared to the control were not statistically significant.

Conclusions

Our finding of reduced TrkB expression in bipolar disorder suggests that dysregulation of TrkB-mediated neurotrophin signaling in the cerebellum may play a role in the pathophysiology of this disease.     

Cardiac sarcoidosis: Recurrent disease in a heart transplant patient following pulmonary tuberculosis infection

Cardiac transplantation is indicated for patients with end-stage cardiomyopathy secondary to cardiac sarcoidosis. Although rare, recurrent disease has been reported in two cases. The current report presents a case of recurrent cardiac sarcoidosis in a patient 45 months postorthotopic heart transplantation and 40 months following reactivation of latent Mycobacterium tuberculosis infection. The patient was the first to have recurrent disease following an infection that has been proposed to be involved in its pathogenesis. The patient’s interval between transplant and recurrence is the longest reported to date.