Interferon Alpha-2b Therapy in Chronic Hepatitis Delta

Background:

Approximately 5% of hepatitis B virus (HBV) carriers are coinfected with hepatitis D virus (HDV). HBV/HDV coinfection is a major cause of cirrhosis and end stage liver disease in chronic HBsAg carriers. The only approved therapy for chronic hepatitis delta is interferon alpha (IFN α) in either pegylated or conventional forms. Although higher doses and longer durations of IFN α therapy in HBV/HDV coinfected patients are currently applied, yet treatment response is low.

Objectives:

We aimed to determine the efficacy of IFN α-2b therapy in patients with HBV/HDV coinfection.

Patients and Methods:

In this cross sectional study, 20 HBsAg carriers with positive Anti-HDVAb and RT-PCR for HDV RNA were recruited and treated for three year duration with 5 million units (MU) of IFN α-2b, three times weekly or one year with 5 MU of IFN α-2b daily. Sustained virological response (SVR) was defined as a negative qualitative HDV RT-PCR, 6 months after treatment cessation.

Results:

Overall, 3 (15%) subjects achieved SVR, 10 cases (50%) relapsed after treatment cessation and 7 (35%) patients did not clear HDV during the treatment.

Conclusions:

HDV coinfection with HBV had very low response rate to high doses and long durations of IFN α-2b therapy.     

Designing a high-performance smart drug delivery system for the synergetic co-absorption of DOX and EGCG on ZIF-8

Due to the extreme pore volume and valuable surface area, zeolitic imidazole frameworks (ZIFs) are promising vehicles that enhance the delivery of therapeutic agents to tissues. Furthermore, these nanoporous materials have high stability in the pH and temperature of the surrounding healthy cells (37 °C and pH = 7) and an exotic potential to deform in carcinogenic environment (T > 37 °C and pH ∼ 5.5), which make them perfect smart drug delivery vehicle candidates. In this work, a series of molecular dynamics (MD) and metadynamics simulations have been performed to gain molecular insight into the mechanisms involved in the process of co-loading of doxorubicin (DOX) and EpiGalloCatechin-3 Gallate (EGCG) on ZIF-8, which form a smart drug delivery system (SDDS). The obtained results revealed that DOX was adsorbed on the carrier mostly through electrostatic interactions (E_coul = ∼−1200 kJ mol⁻¹, E_tot = −1700 kJ mol⁻¹), and EGCG was stacked on ZIF-8 mainly via van der Waals interactions (E_L-J = ∼−600 kJ mol⁻¹, E_tot = ∼−1200 kJ mol⁻¹). It is worth mentioning that the drug–drug L-J interactions (E_L-J = ∼500 kJ mol⁻¹) were also important in the co-loading process. The insertion of DOX and EGCG as additive agents to the initial ZIF-8/EGCG and ZIF-8/DOX systems led to the enhancement of the drug–carrier pair interactions to about ∼−2300 kJ mol⁻¹ and ∼−2000 kJ mol⁻¹, respectively. This finding implied that the drug–drug interactions had a complementary role in the development of SDDS via ZIF-8. From the metadynamics simulation, it was found that the geometry of the drugs is a determining factor in an efficient co-loading SDDS.

Adsorption free energy of a molecule depends on where and how the molecule meets ZIF-8 surface.     

Percutaneous coronary intervention: historical perspectives, current status, and future directions

In the twenty-six years since Gruntzig introduced a simple balloon angioplasty technique, percutaneous coronary intervention has undergone extraordinary growth and has now surpassed bypass surgery in frequency of performance. Several critical breakthrough technologies account for this remarkable progress: intracoronary stents have increased success rates and reduced restenosis, adjunctive antiplatelet therapy has reduced periprocedural complications, and restenosis after stent placement has been effectively treated with local radiation. Most recently, drug-eluting stents coated with cell-cycle inhibitors have shown great promise for further reducing restenosis, possibly to negligible levels.     

Inter-examiner reliability of diplomats in the mechanical diagnosis and therapy system in assessing patients with shoulder pain

Objective:

To investigate the inter-examiner reliability of Mechanical Diagnosis and Therapy (MDT)-trained diplomats in classifying patients with shoulder disorders. The MDT system has demonstrated acceptable reliability when used in patients with spinal disorders; however, little is known about its utility when used for appendicular conditions.

Methods:

Fifty-four clinical scenarios were created by a group of 11 MDT diploma holders based on their clinical experience with patients with shoulder pain. The vignettes were made anonymous, and their clinical diagnoses sections were left blank. The vignettes were sent to a second group of six international McKenzie Institute diploma holders who were asked to classify each vignette according to the MDT categories for upper extremity. Inter-examiner agreement was evaluated with kappa statistics.

Results:

There was ‘very good’ agreement among the six MDT diplomats for classifying the McKenzie syndromes in patients with shoulder pain (kappa = 0.90, SE = 0.018). The raw overall level of multi-rater agreement among the six clinicians in classifying the vignettes was 96%. After accounting for the actual MDT category for each vignette, kappa and the raw overall level of agreement decreased negligibly (0.89 and 95%, respectively).

Discussion:

Using clinical vignettes, the McKenzie system of MDT has very good reliability in classifying patients with shoulder pain. As an alternative, future reliability studies could use real patients instead of written vignettes.     

Screening of different interactions in oxo-manganese porphyrin dimers containing axial N-donor ligands: a theoretical study

A theoretical analysis for describing the dimeric assemblies of high-valent manganese(v)-oxo meso-tetraphenylporphyrin (TPP) ([(TPP)Mn^VO]₂²⁺) and meso-tetrakis(pentafluorophenyl)porphyrin (TPFPP) ([(TPFPP)Mn^VO]₂²⁺) in the presence of axial N-donor ligands is presented. Our theoretical results revealed two types interactions in dimers: a sandwich-like interaction between phenyl rings of porphyrin molecules, and a non-bonded T-shape interaction between nitrogen donors attached to Mn centers. The curvature in the geometry of porphyrin in the [(TPP)Mn^VO]₂²⁺/N-donor system is significantly smaller than that of [(TPFPP)Mn^VO]₂²⁺/N-donor system. Moreover, the Mn–N_(ax) distances in [(TPFPP)Mn^VO]₂²⁺/N-donor system are shorter than those of [(TPP)Mn^VO]₂²⁺/N-donor system. Also, the donor–acceptor interaction between the imidazoles and the Mn centers are stronger than those of the other ligands in both porphyrins. These results are supported by atoms in molecules (AIM) and natural bond orbital (NBO) analysis.

A DFT analysis for describing the dimeric assemblies of high-valent manganese(v)-oxo meso-tetraphenylporphyrin ([(TPP)Mn^VO]₂²⁺) and meso-tetrakis(pentafluorophenyl)porphyrin ([(TPFPP)Mn^VO]₂²⁺) in the presence of axial N-donor ligands is presented.     

Evaluation of 'partnership care model' in the control of hypertension

One of the shared common goals of World Hypertension League (WHL) and World Health Organization (WHO) is the control of hypertension. Despite many local and international interventions, the goal has not been achieved. This study evaluated an intervention based on the partnership care model to control hypertension in a rural population in the north of Iran. The results showed that the intervention was effective in decreasing systolic and diastolic blood pressure and in increasing the rate of controlled hypertensives (based on criteria of WHO/WHL). The intervention also had positive effects on health-related quality of life, body mass index, anxiety, high density lipoprotein level and compliance score. Based on these results, the partnership care model is effective in hypertension control and is recommended as a model to replace previous approaches in hypertension control.     

CYP1B1 mutation profile of Iranian primary congenital glaucoma patients and associated haplotypes

The mutation spectrum of CYP1B1 among 104 primary congenital glaucoma patients of the genetically heterogeneous Iranian population was investigated by sequencing. We also determined intragenic single nucleotide polymorphism (SNP) haplotypes associated with the mutations and compared these with haplotypes of other populations. Finally, the frequency distribution of the haplotypes was compared among primary congenital glaucoma patients with and without CYP1B1 mutations and normal controls. Genotype classification of six high-frequency SNPs was performed using the PHASE 2.0 software. CYP1B1 mutations in the Iranian patients were very heterogeneous. Nineteen nonconservative mutations associated with disease, and 10 variations not associated with disease were identified. Ten mutations and three variations not associated with disease were novel. The 13 novel variations make a notable contribution to the approximately 70 known variations in the gene. CYP1B1 mutations were identified in 70% of the patients. The four most common mutations were G61E, R368H, R390H, and R469W, which together constituted 76.2% of the CYP1B1 mutated alleles found. Six unique core SNP haplotypes were identified, four of which were common to the patients with and without CYP1B1 mutations and controls studied. Three SNP blocks determined the haplotypes. Comparison of haplotypes with those of other populations suggests a common origin for many of the mutations.