Hydroxyapatite nanorods loaded with parathyroid hormone (PTH) synergistically enhance the net formative effect of PTH anabolic therapy

Parathyroid hormone (PTH) has been a major contributor to the anabolic therapy for osteoporosis, but its delivery to bone without losing activity and avoiding adverse local effects remain a challenge. Being the natural component of bone, use of hydroxyapatite for this purpose brings a major breakthrough in synergistic anabolism. This study focuses on synthesis, characterization and evaluation of in vitro and in vivo efficacy of PTH (1-34) adsorbed hydroxyapatite nanocarrier for synergistic enhancement in the anabolic activity of PTH for bone regeneration. The negative zeta potential of this nanocarrier facilitated its affinity to the Ca²⁺ rich bone tissue and solubilization at low pH enhanced specific delivery of PTH to the resorption pits in osteoporotic bone. In this process, PTH retained its anabolic effect and at the same time an increase in bone mineral content indicated enhancement of the net formative effect of the PTH anabolic therapy.     

Cost and sustainability of a successful package of interventions to improve vaccination coverage for children in urban slums of Bangladesh

Objective

To estimate the incremental economic costs and explore satisfaction with a highly effective intervention for improving immunization coverage among slum populations in Dhaka, Bangladesh. A package of interventions based on extended clinic hours, vaccinator training, active surveillance, and community participation was piloted in two slum areas of Dhaka, and resulted in an increase in valid fully immunized children (FIC) from 43% pre-intervention to 99% post-intervention.

Methods

Cost data and stakeholder perspectives were collected January–February 2010 via document review and 10 key stakeholders interviews to estimate the financial and opportunity costs of the intervention, including uncompensated time, training and supervision costs.

Results

The total economic cost of the 1-year intervention was $18,300, comprised of external management and supervision (73%), training (11%), coordination costs (1%), uncompensated staff time and clinic costs (2%), and communications, supplies and other costs (13%). An estimated 874 additional children were correctly and fully immunized due to the intervention, at an average cost of $20.95 per valid FIC. Key stakeholders ranked extended clinic hours and vaccinator training as the most important components of the intervention. External supervision was viewed as the most important factor for the intervention's success but also the costliest. All stakeholders would like to reinstate the intervention because it was effective, but additional funding would be needed to make the intervention sustainable.

Conclusion

Targeting slum populations with an intensive immunization intervention was highly effective but would nearly triple the amount spent on immunization per FIC in slum areas. Those committed to increasing vaccination coverage for hard-to-reach children need to be prepared for substantially higher costs to achieve results.     

Phytochemical analysis and radical scavenging profile of juices of <Emphasis Type="Italic">Citrus sinensis,Citrus anrantifolia</Emphasis>, and <Emphasis Type="Italic">Citrus limonum</Emphasis>

Background

The aim of the current investigation was to identify bioactive secondary metabolites including phenols, tannins, flavonoids, terpinedes, and steroids and compare the phytochemical analysis and antioxidant profile of the juice extracted from the fruits of Citrus sinensis, Citrus anrantifolia, and Citrus limonum.

Results

Phytochemical screening is important for the isolation of new, novel, and rare secondary metabolites before bulk extraction. Phytochemical analysis of the desired plant fruits of family Rutaceae revealed the presence of phenols, flavonoids, reducing sugars, steroids, terpinedes and tannins. The fruits of C. sinensis and C. anrantifolia exhibited the presence of phenols, flavonoids, reducing sugars, steroids, terpinedes and tannins, while the fruits of C. limonum indicated the presence of phenols, flavonoids, reducing sugars, terpinedes, and tannins. The fruits of selected plants were also subjected to antioxidant potential by 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay against ascorbic acid at various concentrations. Among the tested plants, C. sinensis showed promising antiradical effect (84.81%) which was followed by C. Anrantifolia (80.05%) at 100 μg/ml against ascorbic acid (96.36%). The C. limonum showed low antioxidant activity among the three selected plants of family Rutaceae.

Conclusions

The current finding is baseline information in the use of the fruits of selected plants as food supplement which may be due to the presence of antioxidant molecules in the family Rutaceae. Further research is needed in this area to isolate the phenolic constituents which possess ideal antiradical potential.

     

WHAT ARE THE EFFECTS OF DIFFERENT MODES OF EXERCISE TRAINING FOR INTERMITTENT CLAUDICATION? - A COCHRANE REVIEW SUMMARY WITH COMMENTARY

The aim of this commentary is to discuss from a rehabilitation perspective the published Cochrane Review “Modes of exercise training for intermittent claudication”(1) by Jansen SCP et al¹, under the direct supervision of Cochrane Vascular. This Cochrane Corner is produced in agreement with the Journal of Rehabilitation Medicine by Cochrane Rehabilitation.Key words: Cochrane Review Summary, exercise training, intermittent claudication, systematic review, walking     

Kidney protective potential of lactoferrin: pharmacological insights and therapeutic advances

Kidney disease is becoming a global public health issue. Acute kidney injury (AKI) and chronic kidney disease (CKD) have serious adverse health outcomes. However, there is no effective therapy to treat these diseases. Lactoferrin (LF), a multi-functional glycoprotein, is protective against various pathophysiological conditions in various disease models. LF shows protective effects against AKI and CKD. LF reduces markers related to inflammation, oxidative stress, apoptosis, and kidney fibrosis, and induces autophagy and mitochondrial biogenesis in the kidney. Although there are no clinical trials of LF to treat kidney disease, several clinical trials and studies on LF-based drug development are ongoing. In this review, we discussed the possible kidney protective mechanisms of LF, as well as the pharmacological and therapeutic advances. The evidence suggests that LF may become a potent pharmacological agent to treat kidney diseases.     

An enzyme free simultaneous detection of γ-amino-butyric acid and testosterone based on copper oxide nanoparticles

Herein, an easy wet-chemical process was used in basic medium with low temperature to prepare low-dimensional copper oxide nanoparticles (CuO NPs). A variety of optical and structural techniques such as UV-visible, FT-IR, XRD, FESEM, XEDS, and XPS were used to characterize the synthesized CuO NPs in detail. Two sensitive and selective sensor probes for γ-amino-butyric acid (GABA) and testosterone (TST) were achieved after modification; a thin layer of NPs on a flat glassy carbon electrode (GCE). Sensor analytical parameters such as sensitivity (SNT), linear dynamic range (LDR), limit of detection (LOD), limit of quantification (LOQ), robustness, and interference effects, were evaluated for the proposed sensor (GCE/CuO NPs) for GABA and TST, based on a dependable current–voltage technique. Calibration curves were found to be linear (R² = 0.9963 and 0.9095) over a broad concentration range of GABA and TST (100.0 pM to 100.0 mM and 10.0 pM to 10.0 mM, respectively). Sensor parameters – SNT (316.46 and 2848.10 pA μM⁻¹ cm⁻²), LDR (100.0 nM to 10.0 mM and 10.0 pM to 1.0 mM), LOD (≈11.70 and 96.67 pM), and LOQ (39.0 and 322.2 pM) – for GABA and TST were calculated from the calibration plot successively. Preparation of CuO NPs using the wet-chemical technique is a good approach for perspective expansion of NPs-based sensors for the enzyme-free detection of biomolecules. Our sensor probe (GCE/CuO NPs) is applied for the cautious recognition of GABA and TST in real biological samples –human, mouse, and rabbit serum – and achieved good and acceptable results.

An easy wet-chemical process was used to prepare copper oxide nanoparticles which were modified and used as sensor probes for γ-amino-butyric acid and testosterone.     

The SARS-CoV-2 B.1.618 variant slightly alters the spike RBD–ACE2 binding affinity and is an antibody escaping variant: a computational structural perspective

Continuing reports of new SARS-CoV-2 variants have caused worldwide concern and created a challenging situation for clinicians. The recently reported variant B.1.618, which possesses the E484K mutation specific to the receptor-binding domain (RBD), as well as two deletions of Tyr145 and His146 at the N-terminal binding domain (NTD) of the spike protein, must be studied in depth to devise new therapeutic options. Structural variants reported in the RBD and NTD may play essential roles in the increased pathogenicity of this SARS-CoV-2 new variant. We explored the binding differences and structural-dynamic features of the B.1.618 variant using structural and biomolecular simulation approaches. Our results revealed that the E484K mutation in the RBD slightly altered the binding affinity through affecting the hydrogen bonding network. We also observed that the flexibility of three important loops in the RBD required for binding was increased, which may improve the conformational optimization and consequently binding of the new variant. Furthermore, we found that deletions of Tyr145 and His146 at the NTD reduced the binding affinity of the monoclonal antibody (mAb) 4A8, and that the hydrogen bonding network was significantly affected consequently. This data show that the new B.1.618 variant is an antibody-escaping variant with slightly altered ACE2–RBD affinity. Moreover, we provide insights into the binding and structural-dynamics changes resulting from novel mutations in the RBD and NTD. Our results suggest the need for further in vitro and in vivo studies that will facilitate the development of possible therapies for new variants such as B.1.618.

This study explored the binding patterns of the wild type and B.1.618 variant using which revealed that the B.1.618 variant possess a stronger binding affinity for the host ACE2 and escape the neutralizing antibodies.