Caffeic acid phenethyl ester: A review on its pharmacological importance,and its association with free radicals,COVID-19, and radiotherapy

Caffeic acid phenethyl ester (CAPE), a main active component of propolis and a flavonoid, is one of the natural products that has attracted attention in recent years. CAPE, which has many properties such as anti-cancer, anti-inflammatory, antioxidant, antibacterial and anti-fungal, has shown many pharmacological potentials, including protective effects on multiple organs. Interestingly, molecular docking studies showed the possibility of binding of CAPE with replication enzyme. In addition, it was seen that in order to increase the binding security of the replication enzyme and CAPE, modifications can be made at three sites on the CAPE molecule, which leads to the possibility of the compound working more powerfully and usefully to prevent the proliferation of cancer cells and reduce its rate. Also, it was found that CAPE has an inhibitory effect against the main protease enzyme and may be effective in the treatment of SARS-CoV-2. This review covers in detail the importance of CAPE in alternative medicine, its pharmacological value, its potential as a cancer anti-proliferative agent, its dual role in radioprotection and radiosensitization, and its use against coronavirus disease 2019 (COVID-19).     

S-Allyl-Mercapto-Captopril: A Novel Compound in the Treatment of Cohen-Rosenthal Diabetic Hypertensive Rats

J Clin Hypertens (Greenwich). 2010;12:451–455. ^©2010 Wiley Periodicals, Inc. S-allyl-mercapto-captopril (CPSSA) is a conjugate of captopril with allicin, an active principle in garlic with multiple beneficial actions on metabolic syndrome abnormalities, including weight preservation, observed by the authors in fructose-induced hypertensive hyperinsulinemic rats and in Koletsky rats. The aim of the study was to examine blood pressure (BP) and glucose levels in the Cohen-Rosenthal Diabetic Hypertensive (CRDH) model as well as to follow their weight preservation. CRDH rats (n=14) were fed the sugar-rich copper-free diet essential for the development of diabetes mellitus. Two months later BP and blood glucose levels were measured. CPSSA was diluted in drinking water and administered at a final dose of 53.5 mg/kg/d (n=8). Control rats (n=6) received no drug (vehicle group). In contrast to control group, CPSSA prevented progressive weight gain, without a detectable effect on food and water intake. CPSSA was effective in attenuating systolic and diastolic BP (P<0.01) as well as significantly reducing glucose levels (P<0.01). Control rats continued to gain weight, whereas the groups fed CPSSA did not. CPSSA was shown to have additional beneficial effects on improving BP and glucose level, as well as preserving weight gain. The authors conclude that the combined molecule CPSSA integrates the antihypertensive feature of both allicin and captopril, making it a potential antidiabetic and cardiovascular protective agent.     

Dose perturbation of a novel cobalt chromium coronary stent on 32P intravascular brachytherapy: a monte carlo study

Intravascular brachytherapy has been adopted for the indication of in-stent restenosis on the basis of results of clinical trials using mainly stainless steel stents. Recently, a new stent made of cobalt-chromium L-605 alloy (CoCr, p=9.22 g/cm3) (MULTI-LINK VISION) was introduced as an alternative to the 316L stainless steel stent design (SS, p=7.87 g/cm3) (MULTI-LINK PENTA). In this work, we used the Monte Carlo code MCNPX to compare the dose distribution for the 32P GALILEO source in CoCr and SS 8 mm stent models. The dose perturbation factor (DPF), defined as the ratio of the dose in water with the presence of a stent to the dose without a stent, was used to compare results. Both stent designs were virtually expanded to diameters of 2.0, 3.0, and 4.0 mm using finite element models. The complicated strut shapes of both the CoCr and SS stents were simplified using circular rings with an effective width to yield a metal-to-tissue ratio identical to that of the actual stents. The mean DPF at a 1 mm tissue depth, over the entire stented length of 8 mm, was 0.935 for the CoCr stent and 0.911 for the SS stent. The mean DPF at the intima (0.05 mm radial distance from the strut outer surface), over the entire stented length of 8 mm, was 0.950 for CoCr, and 0.926 for SS. The maximum DPFs directly behind the CoCr and SS struts were 0.689 and 0.644, respectively. All DPF estimates have a standard deviation of +/-0.6%(k=2), approximating the 95% confidence interval. Although the CoCr stent has a higher effective atomic number and greater density than the SS stent, the DPFs for the two stents are similar, probably because the metal-to-tissue ratio and strut thickness of the CoCr stent are lower than those of the SS stent.     

In vitro performance of the novel coronary sinus AutoRetroPerfusion Cannula

Myocardial salvage through coronary sinus intervention has been documented. The AutoRetroPerfusion Cannula is a novel device that is able to perfuse the coronary bed retrogradely through the coronary sinus with arterial blood generated from a peripheral artery with no need for a pump. The cannula consists of a distal end that, once secured in the coronary sinus, opens an umbrella-like membrane to create pressure in the coronary sinus, and at the same time has small channels directed backwards to the right atrium to provide pressure relief. The cannula is introduced from the axillary vein under local anesthesia and the proximal end, which consists of a graft, is anastomosed to the axillary artery to start autoperfusion once the distal end is secured in the coronary sinus and the occluding membrane is open. The AutoRetroPerfusion Cannula was tested in the in vitro mock loop under 50-120 mm Hg of proximal pressure and 50, 100, and 150 ml/min of total flow in the cannula. We were able to achieve the nominal design point of 40-80 mm Hg of distal pressure and 50-150 ml/min of distal flow by adjusting the number, diameter, and length of the small backwards channels.     

A segmented 32P source Monte Carlo model to derive AAPM TG-60 dosimetric parameters used for intravascular brachytherapy

A new high dose rate 20 mm 32P intravascular brachytherapy (IVB) beta source used with automated stepping has recently been introduced. The AAPM Task Group 60 recommends that beta IVB sources should have well characterized dosimetric parameters in water. In this study, Monte Carlo simulations (MCNPX v 2.4) were used to derive these parameters for a 2 mm source segment rather than the entire 20 mm source to ensure the correct formulation using the traditional TG-60 and TG-43 polar coordinate system (r, theta) parameters. The dose rate at the reference depth of 2 mm, the radial dose function, and the anisotropy function were generated for the 2 mm 32P source segment at the mid-plane, distal edge and proximal edge of the original 20 mm source. Our results indicate that the anisotropy of the 2 mm distal and proximal segments are the same, but differ from that of the mid-plane segment due to the perturbation of the adjacent tungsten marker. Using the TG-60 formulation of the mid-plane and edge segments resulted in dose distributions similar to those obtained for a 20 mm linear beta source model. The segmented formulation provides a method consistent with the familiar TG-60 formulation and ability to calculate the dose-distribution inside curved vessels.     

Adenosine A(2A) receptor ligation inhibits osteoclast formation

Adenosine is generated in increased concentrations at sites of injury/hypoxia and mediates a variety of physiological and pharmacological effects via G protein-coupled receptors (A(1), A(2A), A(2B), and A(3)). Because all adenosine receptors are expressed on osteoclasts, we determined the role of A(2A) receptor in the regulation of osteoclast differentiation. Differentiation and bone resorption were studied as the macrophage colony-stimulating factor-1-receptor activator of NF-κB ligand formation of multinucleated tartrate-resistant acid phosphatase (TRAP)-positive cells from primary murine bone marrow-derived precursors. A(2A) receptor and osteoclast marker expression levels were studied by RT-PCR. Cytokine secretion was assayed by enzyme-linked immunosorbent assay. In vivo examination of A(2A) knockout (KO)/control bones was determined by TRAP staining, micro-computed tomography, and electron microscopy. The A(2A) receptor agonist, CGS21680, inhibited osteoclast differentiation and function (half maximal inhibitory concentration, 50 nmol/L), increased the percentage of immature osteoclast precursors, and decreased IL-1β and tumor necrosis factor-α secretion, an effect that was reversed by the A(2A) antagonist, ZM241385. Cathepsin K and osteopontin mRNA expression increased in control and ZM241385-pretreated osteoclasts, and this was blocked by CGS21680. Micro-computed tomography of A(2A)KO mouse femurs showed a significantly decreased bone volume/trabecular bone volume ratio, decreased trabecular number, and increased trabecular space. A(2A)KO femurs showed an increased TRAP-positive osteoclast. Electron microscopy in A(2A)KO femurs showed marked osteoclast membrane folding and increased bone resorption. Thus, adenosine, acting via the A(2A) receptor, inhibits macrophage colony-stimulating factor-1-receptor activator of NF-κB ligand-stimulated osteoclast differentiation and may regulate bone turnover under conditions in which adenosine levels are elevated.     

Laparoscopic nephron sparing surgery: evolution in a decade

OBJECTIVE: To present our experience with laparoscopic nephron sparing surgery (NSS) over a decade. METHODS: Seventy-eight patients underwent NSS since 1994. Two techniques were used-partial nephrectomy without ischemia (group 1) in 29 patients, and with ischemia (group 2) which was in cold or warm ischemia in 24 and 25 patients respectively. The mean tumour size was 1.97 and 2.2 cm in groups 1 and 2 respectively. Renal reconstruction evolved in our hands during this period. We changed many technical details and now we depend more on clips for securing the sutures rather than free hand knotting. RESULTS: The mean operative time was 162 and 216 minutes in groups 1 and 2 respectively. Mean ischemia time for patients with cold and warm ischemia was 44.9 and 33.8 minutes respectively. 3 patients in group 2 were converted to open surgery. Mean blood loss was 254 and 212 ml for group 1 and 2 respectively with two major bleedings in group 2. Minor intra-operative complication occurred in 3 patients, and major and minor postoperative complication in 15 patients. At a mean follow-up of 23.9 and 12.2 months for groups 1 and 2 respectively there was no recurrence. CONCLUSION: Warm and cold ischemia have widened the indications for laparoscopic NSS to more complex tumours and allow renal reconstruction with acceptable complication rate.     

Efficacy and safety of the perclose closer s device after neurointerventional procedures: prospective study and literature review

BACKGROUND AND PURPOSE: The purpose of this study was to examine the efficacy and safety of the 6F Closer S device (Perclose; Redwood City, CA) versus manual compression to close arteriotomy sites after neurointerventional procedures in both virgin vessels and those previously treated with the device. METHODS: This single-center, multiple-operator, controlled, prospective study included 475 procedures (337 patients) with the device and 79 procedures (79 patients) with manual compression. A substantial number of patients receiving anticoagulation and/or antiplatelet medications were included. Efficacy and safety were evaluated on the basis of the rate of hemostatic success and the incidence of clinically significant complications. The literature was reviewed by using MEDLINE. RESULTS: Overall success rates were 95% in the device group versus 96% in the manual-compression group (P = 0.78), and clinically relevant complication rates were 0.6% versus 2.5%, respectively (P = 0.15). Success rates significantly declined in vessels previously treated with the device three or more times. However, complication rates did not significantly change. Literature review yielded 12 articles reporting complication rates of 3.2-35% for the device and 2.3%-33.3% for manual compression. CONCLUSION: The device was safe and effective for closing arteriotomy sites in patients undergoing neurointerventional procedures, including those receiving anticoagulation/antiplatelet therapy or those previously treated with the device one or two times.