Development and in vivo evaluation of chitosan nanoparticles for the oral delivery of albumin

Albumin is used as a plasma expander in critically ill patients and for several other clinical applications mainly via intravenous infusion. Oral administration of albumin can improve patient compliance although limited oral bioavailability of proteins is still a major challenge. Although nanomaterials have been extensively utilized for improving oral delivery of proteins, albumin has been utilized only as either a model drug or as a carrier for drug delivery. In the current study, for the first time, chitosan nanoparticles have been developed and extensively optimized to improve oral bioavailability of albumin as a therapeutic protein. Several characterizations have been performed for the albumin-loaded nanoparticles (e.g. drug encapsulation efficiency, DSC, FTIR, particle size, zeta potential, morphology, release kinetics, and enzymatic stability). Nanosized spherical particles were prepared and demonstrated high stability over three months either in a powdered form or as suspensions. Sustained release of albumin over time and high enzymatic stability as compared to the free albumin were observed. In vivo, higher serum concentrations of albumin in normal rabbits and cirrhotic rats were attained following oral and intraperitoneal administrations of the albumin-loaded nanoparticles as compared to the free albumin. The nanoparticles developed in the current study might provide efficient nanovehicles for oral administration of therapeutic albumin.     

Evaluation of cognitive function in systemic sclerosis patients: a pilot study

Clinical Rheumatology - To investigate cognitive dysfunction in adult patients with systemic sclerosis (SSc) who had no known clinical neurological manifestations and to relate it with other...     

A new fast nonlinear modeling of soft tissue for surgical simulation

In this paper, soft tissue is modeled by a mass–spring–damper system and tissue deformations under the compression of surgical instruments are simulated. For this purpose, soft tissue confined in a cubic plastic mold is studied using a nonlinear viscoelastic model. Displacements resulting from probe insertions are measured and modeled for use in robotic surgery. Data is collected on bovine sirloin using the Instron hardness tester. The model’s dynamic equations are obtained in the form of ordinary differential equations. The external force is considered as the input and the resulting deformation as the output of the model. Simulation results are compared with laboratory findings, and the nonlinear model’s unknown parameters are estimated. The threshold force and displacement before the tearing of the soft tissue are respectively determined by analyzing the force–time and displacement–time diagrams obtained for the test samples.     

Work-Related Psychosocial Hazards Among Emergency Medical Responders (EMRs) in Mansoura City

Purpose:

This research was done to assess levels of psychosocial stress and related hazards [(burnout, depression, and posttraumatic stress disorder (PTSD)] among emergency medical responders (EMRs).

Materials and Methods:

A comparative cross-sectional study was conducted upon (140) EMRs and a comparative group composed of (140) nonemergency workers. The groups studied were subjected to semistructured questionnaire including demographic data, survey for job stressors, Maslach burn out inventory (MBI), Beck depression inventory (BDI), and Davidson Trauma scale for PTSD.

Results:

The most severe acute stressors among EMRs were dealing with traumatic events (88.57%), followed by dealing with serious accidents (87.8%) and young victims (87.14%). Chronic stressors were more commonly reported among EMRs with statistically significant differences (P < 0.05) except for social support with colleagues and supervisors. EMRs had statistically significant higher levels of emotional exhaustion (EE) (20%) and depersonalization (DP) (9.3%) compared with comparative group (4.3%, 1.4% respectively). Also, there was no statistically significant difference between two groups as regards lower personal achievement or depression symptoms (P > 0.05). There was increased risk of PTSD for those who had higher stress levels from death of colleagues [odds ratio (OR) [95% confidence interval (CI)] = 2.2 (0.7-7.6), exposure to verbal or physical assault OR (95% CI) = 1.6 (0.5-4.4) and dealing with psychiatric OR (95% CI) 1.4 (0.53.7) (P > 0.05)

Conclusion:

EMRs group had more frequent exposure to both acute and chronic work-related stressors than comparative group. Also, EMRs had higher levels of EE, DP, and PTSD compared with comparative group. EMRs are in need for stress management program for prevention these of stress related hazards on health and work performance.     

Ablation of Breast Cancer Cells Using Trastuzumab‐Functionalized Multi‐Walled Carbon Nanotubes and Trastuzumab‐Diphtheria Toxin Conjugate

Trastuzumab (Herceptin^®) is a monoclonal antibody (mAb) for specific ablation of HER2‐overexpressing malignant breast cancer cells. Intensification of antiproliferative activity of trastuzumab through construction of immunotoxins and nano‐immunoconjugates is a promising approach for treatment of cancer. In this study, trastuzumab was directly conjugated to diphtheria toxin (DT). Also, conjugates of trastuzumab and multiwalled carbon nanotubes (MWCNT) were constructed by covalent immobilization of trastuzumab onto MWCNTs. Then, antiproliferative activity of the fusion constructs against HER2‐overexpressing SK‐BR‐3 and also HER2‐negative MCF‐7 cancer cell lines were examined. Cells treated with trastuzumab‐MWCNT conjugates were irradiated with near‐infrared (NIR) light. Efficient absorption of NIR radiation and its conversion to heat by MWCNTs can be resulted to thermal ablation of cancerous cells. Our results strongly showed that both trastuzumab‐MWCNT and trastuzumab‐DT conjugates were significantly efficient in the specific killing of SK‐BR‐3 cells. Targeting of MWCNTs to cancerous cells using trastuzumab followed by exposure of cells to NIR radiation was more efficient in repression of cell proliferation than treatment for cancer cells with trastuzumab‐DT. Our results also showed that conjugation linkers can significantly affect the cytotoxicity of MWCNT‐immunoconjugates. In conclusion, our data demonstrated that trastuzumab‐MWCNT is a promising nano‐immunoconjugate for killing of HER2‐overexpressing cancerous cells.     

Connectivity Defects and Collective Assemblies in Model Metallo‐Supramolecular Dual‐Network Hydrogels

Double network hydrogels are composed of chemical and physical bonds, whose influences on the macroscopic material properties are convoluted. To decouple these, a model dually crosslinked network with independently tunable permanent and reversible crosslinks is introduced. This is realized by interlinking linear and tetra‐arm poly(ethylenegycol) (PEG) precursors with complementary reactive terminal groups. The former also carries a terpyridine ligand at each end, which forms reversible metallo‐supramolecular bonds upon addition of metal ions. These dual networks display different types and amounts of network defects, as studied by light scattering and proton double‐quantum (DQ) NMR. Dynamic light scattering suggests that the network mesh size decreases upon introduction of metal ions, as supported by a decrease of the residual dipolar coupling constant in NMR. Static light scattering indicates larger static inhomogeneities in those networks composed of stronger ions. This is complemented by a fast solid‐like component in the DQ buildup in NMR, attributed to the formation of nanoscopic clusters of charged complexes. The DQ buildup curves also suggest that the presence of strong physical bonds increases the fraction of mobile segments, like loops and dangling ends. This combined study unveils the interplay of chemical and physical bonds toward the formation of a hierarchical structure.     

Mental and personality disorders in infertile women with polycystic ovary: a case-control study

BackgroundPolycystic Ovarian Syndrome (PCOS) is one of the most common causes of infertility in women.ObjectiveThe current study investigated mental and personality disorders in infertile women with and without PCOS.MethodsThis case-control study evaluated 400 infertile women who referred to the Infertility Center in Babol city (North of Iran). Participants were categorized into the case group (201 PCOS) and the control group (199 without PCOS). All of the participants completed the Millon Clinical Multi-axial Inventory-III (MCMI-III).ResultsThe mean scores for clinical personality patterns were significantly higher for six personality disorders (schizoid, avoidant, antisocial, depressive, sadistic, and negativistic) and for three classes of severe personality disorder patterns (schizotypal, borderline, and paranoid) in infertile women with PCOS than in women without PCOS. The mean scores for eight clinical disorders (somatoform, manic disorder, dysthymia, alcohol-dependence, drug-dependence, post-trauma stress disorder, major depression, and delusion disorder) were also higher in infertile women with PCOS than in women without PCOS.ConclusionThe scores of many mental and personality disorders are higher in infertile women with PCOS than in women without PCOS. Thus, clinicians should prioritize recognizing and treating psychological problems of infertile women with PCOS.