Coronary artery bypass surgery without blood transfusion; is it possible?

BACKGROUND: Coronary artery bypass surgery is the most commonly performed cardiac operation and approximately 40-70% of patients require a blood transfusion despite improvements in cardiac surgical techniques. Some preventive perfusion methods to avoid transfusions are described, such as acute normovolemic hemodilution, retrograde autologous priming, and usage of integrated arterial filter oxygenator. AIMS: We combined these three techniques (triple combination technique) to evaluate whether it is possible to avoid blood transfusions in adult patients undergoing coronary artery bypass surgery. MATERIALS AND METHODS: A total of 300 consecutive patients were included in this randomized controlled trial. 150 patients (Group 1) were operated with triple combination technique, The other 150 patients (Group 2) were operated with standard cardiopulmonary bypass technique. The two groups were compared in terms of peroperative and postoperative blood product use. RESULTS: Ninety-two percent (92%) of the patients (Group 1) undergoing coronary artery bypass surgery did not require any blood transfusion. Only 8% of the patients required erythrocyte suspension or fresh frozen plasma transfusion. In Group 2, 58% of patients required blood transfusions. The difference between two groups was statistically significant (p < 0,05). CONCLUSION: Triple combination technique is safe and cost-effective in coronary artery bypass surgery. We think that most of the patients could be operated without blood transfusion with this technique.

Alzheimer's drug Memantine inhibits metastasis and p-Erk protein expression on 4T1 breast cancer cells.

OBJECTIVES: Drug repurposing studies enable shorter routes to the clinic by skipping the steps like in vitro  in vivo screening, chemical optimization and toxicological studies. In our study, we investigated the potent anti-cancer effect of Alzheimer's drug Memantine on 4T1 breast cancer cells. METHODS: Memantine's effect on proliferation of 4T1 cells was evaluated by using the MTT assay. Memantine inhibited 4T1 cell proliferation in a concentration- dependent manner at 24 and 48 hours. We investigated the drug's effect on the protein expressions of Bax, Bcl-2, Casp-3, Casp-9, E-Cad, Vimentin, B-Cat, GSK3B, p-ERK, ERK, p-GS, GS that are involved in apoptosis, metastasis and cell survival. RESULTS: Memantine altered the Bcl-2, Bax, Casp3, Casp-9 apoptotic protein expression levels. We found that memantine inhibited p-Erk expression and that result suggested a plausible mechanism of action for memantine's antineoplastic effect. Memantine also inhibited wound closure at 24 h, significantly (p = 0.0055). CONCLUSIONS: Memantine inhibited 4T1 breast cancer cell proliferation at significantly lower doses than mostly studied re-purposed drug Metformin. Therefore, we believe that memantine might hold a great promise as a new repositioned drug in cancer treatment and it is our further interest to investigate its effects in vivo (Fig. 3, Ref. 22).

Memantine induces apoptosis and inhibits cell cycle progression in LNCaP prostate cancer cells.

Deregulated cancer cell metabolism plays an important role in cancer progression. Cancer cell metabolism has been in the centre of attention in therapeutical cancer cell targeting. Repurposed chemical agents, such as metformin and aspirin, have been studied extensively as preventive and therapeutic agents. Metformin is Food and Drug administration (FDA)-approved antidiabetic drug cheaper than other chemotherapeutic agents that were shown to have anticancer effects. Memantine is an FDA-approved Alzheimer's drug. Drug repositioning studies offer wide range of benefits, such as reduced time, cost and risk over de novo drug discovery. Therefore, we aimed to target glucose and glutamine metabolism in androgen-dependent LNCaP cells by using metformin and memantine and investigate these agents' effects on prostate cancer cell proliferation in vitro. We evaluated the effects of metformin and memantine on the protein expression levels of genes that play significant roles in apoptosis and cell cycle progression (Casp3, Casp9, Bcl-2, Survivin, Bax, c-Myc, HIF1A, CCND1, CDK4 and GAPDH) by Western blotting. Alzheimer's drug memantine exerted cytotoxic effects at 0.25 mM and metformin at 2.5 mM. We identified for the first time that memantine exerts antineoplastic activity (0.25 mM) by triggering Bax-dependent pathway of apoptosis. In addition to that both molecules have shown similar patterns on pro- and anti-apoptotic protein expression levels, such as Bcl-2, Casp3, Survivin and Bax. Our preclinic results indicate that memantine might be used as a new repositioned drug in cancer treatment. Beyond targeting glucose metabolism, glutamine metabolism also holds great promise for a potential treatment option.

Arterial stiffness and cardiac functions in patients with chronic venous disease.

AIM: Although the venous system is in direct continuity with the heart and the arterial system, it is not known whether chronic venous disease (CVD) has any impact on either of these. The aims of this study were to investigate the global functions of the left and right heart, and also arterial stiffness parameters in patients with CVD. METHODS: Forty-eight patients with primary stage C4-C6 CVD were enrolled into the study. The control group consisted of 39 age/sex and Body Mass Index matched healthy volunteers. All of the patients underwent detailed echocardiographic examination with further focus on Doppler and tissue Doppler (TD) parameters of the left and right ventricle. Arterial stiffness was evaluated via applanation tonometry in each patient. RESULTS: The left atrial area (LAA) and interventricular septum thickness were slightly increased in patients with CVD. Regarding Doppler and tissue Doppler measurements of the LV, all of the parameters were similar among the groups, while RV tissue Doppler systolic velocity and TAPSE were higher in patients with CVD. Among the arterial stiffness parameters, central aortic pressure, augmentation index, and pulse wave velocity were slightly higher in patients with CVD. CONCLUSION: The results of this study indicated that CVD may be associated with a subclinical disease state in the arterial system and also in the heart. Further studies are needed to confirm this association and to describe the possible mechanisms.

Genetic characterization of Fusarium graminearum and F. culmorum isolates from Turkey by using random-amplified polymorphic DNA.

Five Fusarium graminearum and 12 F. culmorum isolates, primarily pathogenic species of Fusarium head blight, were obtained from naturally infected wheat from various agro-ecological regions of Turkey. Genotyping of the isolates was carried out using random-amplified polymorphic DNA (RAPD). Sixty-five 10-mer oligonucleotide primers were used to amplify the RAPD markers. Among them, 50 primers produced strong and reproducible DNA amplicons. The remaining primers generated either insufficient or no amplification patterns. In total, 1200 fragments were scored, 311 of which were determined to be polymorphic and unique to the isolates. The produced RAPD markers ranged from 0.2 to 5 kb. The mean genetic similarity values of the F. graminearum and F. culmorum isolates were 61.5 and 65%, respectively. The similarity coefficient was 43 to 76.1% among F. graminearum isolates and 49 to 81.1% among F. culmorum isolates. Genetically, the most similar F. graminearum isolates were F6 and F7 (76.1%), which originated from the same agro-ecological region (Sakarya). The most similar F. culmorum isolates were F20 and F21 (81.1%), which were from different geographic regions (Bilecik and UÅYak, respectively). Moreover, interspecific variation between the two species was determined to be 86.3 to 93.3%. Cluster analysis generated two branched groups, each containing isolates of one species, except F13 of F. culmorum. The sequencing of stable and reproducible monomorphic and polymorphic RAPD markers indicated that the Fusarium genome shared high similarity (105-625 bit scores) with the genomes of other organisms as well as with the F. graminearum reference genome.