Development and evaluation of a pH-responsive and water-soluble drug delivery system based on smart polymer coating of graphene nanosheets: an in silico study

The objective of this study is to develop a controlled and water-soluble delivery system for doxorubicin (DOX) based on the coating of graphene (G) with a smart polymer. A combination of polyethyleneimine (PEI) and G–DOX is investigated by performing density functional theory (DFT) calculations and molecular dynamics (MD) simulations. Several parameters have been employed to evaluate the effect of PEI on the adsorption and release mechanisms of DOX. The obtained results indicated that the binding energy of the drug molecule on G in the presence of PEI is enhanced by about 20% under neutral conditions, whereas the drug absorption becomes weaker in an acidic environment so that DOX could be separated from the carrier surface using near-infrared radiation (NIR). Based on the atom in molecule (AIM) theory, two hydrogen bonds with strengths of about −12.59 and −39.99 kJ mol⁻¹ have been established. Furthermore, evaluating the dynamic behavior of the designed systems in water solution shows that the polymer in physiological pH rapidly adsorbed on the drug–carrier complex. However, at acidic pH, it is quickly desorbed from the carrier surface and the G–DOX complex can be exposed to cancer cells. The obtained results of the present research may be used in future experimental work to design smart DDSs.

The objective of this study is to develop a controlled and water-soluble delivery system for doxorubicin (DOX) based on the coating of graphene (G) with a smart polymer.     

Familial predisposition and cosegregation analysis of adult obstructive sleep apnea and the sudden infant death syndrome

Previous studies suggest a familial link between adult obstructive sleep apnea syndrome (OSAS) and sudden infant death syndrome (SIDS). However, most of these studies were hampered by the availability of too few cases of SIDS to draw conclusions. To examine the familial nature of this association in Iceland, hospital-based lists of all patients who were diagnosed with OSAS (n = 2,350) and SIDS (n = 58) from 1979 to 1998 were used to separately determine the familial occurrence of OSAS and SIDS and to search for evidence of cosegregation of these conditions in Icelandic families, using a nationwide genealogy database. The risk ratio for a first-degree relative of a patient with OSAS was 2.0 (1.7-2.8, 95% confidence interval). The risk ratio of the more severely affected patients with OSAS was slightly higher (2.3). Likewise, the kinship coefficient (KC) for the OSAS patient group, which determines the relatedness of the patients, was significantly larger than the mean KC of 1,000 matched control groups. Estimation of the KC for the SIDS group showed a trend toward significance when compared with control groups, but after excluding one of the half-siblings in the SIDS group from the analysis, the difference did not show any trend toward significance. Although the results of the analysis of the relatedness between all patients with OSAS and infants who died of SIDS were not significant, a trend toward significance was evident when the data were separately analyzed for the more severely affected patients with OSAS. Collectively, these results demonstrate a strong familial component in OSAS and suggest that infants who died of SIDS may have shared some of the same susceptibility factors with OSAS.     

Distribution of IL28B Genotypes in Iranian Patients with Chronic Hepatitis C and Healthy Individuals

Background

IL28B polymorphism is recognized as one of the most prominent predictors of hepatitis C spontaneous and treatment-induced clearance. Interestingly, the favorable genotypes of IL28B are found to be more frequent in Asian ethnicity than Caucasian and African populations, respectively. A few studies reported that there is a mysterious association between the IL28B polymorphism and the hepatitis C virus (HCV) genotype in patients with chronic hepatitis C but they did not give any reason for this phenomenon.

Objectives

The foremost purpose of this study was to compare the distribution of IL28B genotypes between Iranian healthy individuals and patients with chronic hepatitis C.

Patients and Methods

In this study, 921 patients with chronic hepatitis C and 142 healthy individuals were included. The IL28B rs12979860 and rs8099917 polymorphisms were genotyped using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method.

Results

The frequency of IL28B rs12979860 CC, CT, and TT genotypes in chronic hepatitis C patients was 38%, 48.8%, and 13.2% and in healthy individuals was 43.7%, 48.6%, and 7.7%. Also, the frequency of IL28B rs8099917 TT, GT, and GG genotypes in chronic hepatitis C patients was 58.3%, 37.1%, and 4.6% and in healthy individuals was 64.1%, 32.4% and 3.5%. The differences in the distribution of IL28B rs12979860 and rs8099917 genotypes between patients with chronic hepatitis C and healthy individuals were not statistically significant. When we compared the distribution of IL28B genotypes between the healthy group and the HCV infected patients by HCV genotype, we found 9.8% higher frequency of rs12979860 CC genotype in the healthy individuals than HCV genotype 1 infected patients (P = 0.03) however there was no significant difference in the distribution of rs12979860 genotypes between the healthy and HCV genotype 3 infected groups (P = 0.46).

Conclusions

It seems that the impact of IL28B polymorphism on the spontaneous clearance of HCV genotype 1 is more prominent than HCV genotype 3 which results in the observation of higher rs12979860 C allele frequency in chronic hepatitis C patients with HCV genotype 3 than HCV genotype 1.     

In the current era, complete revascularization improves survival after coronary artery bypass surgery

BACKGROUND: Complete revascularization has been the standard for coronary bypass grafting. However, surgical intervention has evolved with increasing use of arterial conduits and off-pump techniques. METHODS: Patients undergoing non-redo bypass surgery from January 1998 through December 2000 were followed up with questionnaires and telephone contact. Incomplete revascularization was defined as absence of bypass grafts placed to a coronary territory supplied by a vessel with 50% or greater stenosis. RESULTS: One thousand thirty-four patients were followed for a mean of 3.3 +/- 1.6 years. Complete revascularization was found in 937 (90.6%) patients, and incomplete revascularization was found in 97 (9.4%) patients. Eight hundred twenty-seven (80.4%) patients underwent on-pump operations, and 207 (19.6%) underwent off-pump operations. Incomplete revascularization was more prevalent in off-pump versus on-pump operations (21.7% vs 6.3%, P < .001). Multivariable Cox regression analysis indicated that in-hospital cerebrovascular accidents (hazard ratio, 5.49; P < .001), chronic obstructive pulmonary disease (hazard ratio, 1.97; P = .019), and incomplete revascularization (hazard ratio, 1.85; P = .040) predicted an increased hazard (risk) of cardiac death. Left internal thoracic artery (hazard ratio, 0.38; P = .047), right internal thoracic artery (hazard ratio, 0.25; P = .019), and radial artery (hazard ratio, 0.36; P < .001) grafting reduced the risk of cardiac death. The 5-year unadjusted survival rate was 52.6% versus 82.4% in patients undergoing incomplete and complete revascularization ( P < .001), with cardiac survival rates of 74.5% versus 93.1%, respectively ( P < .001). However, this difference in cardiac survival was smaller in octogenarians with incomplete versus complete revascularizations (77.4% vs 87.6%, P = .101) and was essentially absent in off-pump versus on-pump operations if complete revascularization was achieved in both cases (93.6% vs 93.1%, P > .200). CONCLUSIONS: Complete revascularization and arterial grafting improve 5-year survival. Off-pump techniques do not affect survival. Complete revascularization should be performed whenever possible.     

Lack of evidence for contribution of intron4a/b polymorphism of endothelial nitric oxide synthase (NOS3) gene to plasma nitric oxide levels

OBJECTIVE: Nitric oxide (NO) is synthesized from L-arginine by endothelium nitric oxide synthase (NOS3). It has been shown that reduced NO synthesis in endothelial cells has been implicated in the development of coronary atherosclerosis. We hypothesized that polymorphisms of NOS3 gene might be associated with increased susceptibility of coronary artery disease (CAD) and plasma NO concentrations. METHODS AND RESULTS: We studied the NOS3 intron4 gene polymorphism in 141 unrelated CAD patients with positive coronary angiograms in the Shahid Rajaee Heart Hospital and 159 age-matched control subjects without a history of symptomatic CAD. The NOS3 gene polymorphism was analysed by polymerase chain reaction. Plasma NO was also determined. The genotype frequencies for NOS34a/b polymorphism differed significantly between CAD patients and controls (P = 0.041). Mean plasma NOx concentration was significantly higher (P = 0.0009) in CAD patients (87.5 microM) than in controls (62.7 microM). Mean plasma NOx concentrations in the subjects with 4a allele and in the subjects without 4a allele were not significantly different. Plasma lipids, except HDL-C were also remarkably increased in the CAD group. CONCLUSIONS: The present study provides evidence that the intron4a/b polymorphism of the NOS3 gene is associated with CAD. Mean plasma NO was higher in CAD patients than in control subjects. The NOS34a/b polymorphism was not associated with increased plasma NO.     

Non–surgical management of abdominal ectopic pregnancy with uterine artery embolization

Abdominal pregnancy is a rare but life-threatening variation of ectopic pregnancy that is often treated with laparoscopic management; however, we present a case successfully treated using only minimally invasive techniques. A 36-year-old female G1P0 with a history of infertility is diagnosed with 11-weeks abdominal pregnancy by transvaginal ultrasound. She presented with vaginal bleeding and abdominal pain, and her beta-human chorionic gonadotropin was 53,680 mIU/mL. The location of the fetal sac was not amenable to surgery or percutaneous injection. We performed bilateral uterine artery embolization and subsequent intramuscular methotrexate injection. The procedure was successful with no complications. The patient was followed at postoperative week 11, and beta-human chorionic gonadotropin was 2 mIU/mL, and at 3 months, a transvaginal ultrasound revealed resolution of the abdominal pregnancy.     

Combined transhepatic and transjugular approach for mechanical thrombectomy of massive TIPS thrombosis

Transjugular intrahepatic portosystemic shunt (TIPS) is a well-validated decompressive therapy option to manage ascites and variceal bleeding secondary to portal hypertension. Complications following TIPS procedures include hepatic encephalopathy, liver failure, and TIPS dysfunction. TIPS dysfunction is due to occlusion or stenosis of the TIPS shunt and can be caused by acute or chronic thrombosis. TIPS thrombosis is often treated with mechanical thrombectomy or catheter-directed thrombolytic therapy. Most cases of in-stent occlusion can be treated via a transjugular approach with recanalization or placement of additional stents. We present a case of a 72-year-old female who presented with worsening ascites 17 months after initial TIPS procedure; she was found to have a large thrombus completely occluding the TIPS stent. In our case, a combined transhepatic and transjugular approach was required for TIPS revision given the extent of well-organized clot located near the hepatic venous end of the stent, resulting from prolonged stent occlusion. This was an extremely challenging scenario with two overlapping covered stents and a bare metal stent at the hepatic venous end in the setting of chronic thrombosis and a well-organized fibrous cap. The case highlights the need for optimal initial placement of the primary TIPS shunt to avoid the need for subsequent complex interventions to maintain TIPS shunt patency.     

Rapid 3D reconstruction guided embolization for catastrophic bleeding following vacuum assisted breast biopsy; A case report and review of the literature

The most clinically significant complication associated with stereotactic core needle biopsy of the breast is hematoma formation, which only occurs in less than 1% of biopsies and may require treatment. Cases of uncontrollable bleeding, refractory to repeated compression, resulting from biopsy are exceedingly rare. We present a case of catastrophic, uncontrollable bleeding and large hematoma formation resulting from stereotactic vacuum-assisted breast biopsy of a breast mass identified in screening mammography. Percutaneous embolization was planned and guided using 3D reconstructions from computed tomographic angiography, and bleeding was successfully controlled with micro-coil embolization.