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Vanillylmandelic acid, a catecholamine end-metabolite, has been shown to have several biological properties in previous studies, despite considered biologically inactive. We examined the potential effects of vanillylmandelic acid on the ischemic heart following myocardial infarction and reperfusion on a rat model. Thirty-four female Wistar rats were randomized into two groups, control and experimental. They were anesthetized and subjected to myocardial infarction through left anterior descending artery ligation. A previously studied dose of vanillylmandelic acid (10 mg/kg) was administered and the following parameters were studied during ischemia and reperfusion: a) mortality b) severity of ventricular tachyarrhythmias c) premature ventricular contractions and d) heart rate. Administration of vanillymandelic acid significantly reduced the severity of ventricular tachyarrhythmias and mortality rate during reperfusion, while it did not affect any other of the parameters studied. In conclusion, reperfusion injury was blunted through vanillylmandelic acid administration, which seems to be mediated by parasympathetic activation.

The cytotoxic and antitumour activities of five organotin complexes (1–5) with o-hydroxy-benzoic or p-hydroxy-benzoic acids were evaluated in a series of in vitro and in vivo experiments. All complexes exhibited strong cytotoxic activity against all cancer cells lines, whereas complexes 1, 2 and 4 induced apoptosis at significantly lower doses than complexes 3 and 5. Human cancer cells treated with increasing concentrations of complexes 1, 2 and 4 gradually lost their ability to form colonies. Only complexes 1 and 2 inhibited colony formation efficiency in rat leiomyosarcoma cells. Histopathology of liver and kidney showed mild damage and lung oedema after a single injection of 10 mg/kg body wt of complex 1 to Wistar rats. At higher doses (100 mg/kg body wt) brain stem oedema was observed. Daily administration of tumour-bearing Wistar rats (leiomyosarcoma) with 1 mg/kg body wt of complex 1 until death reduced the mean tumour growth rate by more than 3× fold and prolonged mean survival time by 120%. These findings indicate that the organotin complexes with ortho- or para-hydroxy-benzoic acids possess potent cytotoxic and antitumour activity and they could be used as potential chemotherapeutic agents.

The aim of this study was to investigate the cytotoxic effect cisplatin in combination with epigallocatechin-3-gallate (EGCG) on leiomyosarcoma cells (LMS cells) in order to identify a less toxic but equally effective alternative. Assays for cell proliferation, colony formation efficiency, induction of apoptosis and cell cycle arrest were performed using the IC50 of cisplatin (8.6 μΜ) as a reference value and a concentration of EGCG (30 μΜ) that caused a non-significant reduction in cell proliferation. Pre-treatment of cells with EGCG for 24 h before the addition of cisplatin increased cytotoxicity up to 8.5% (p

Background. Cisplatin (cis-diamminedichloroplatinum) is a widely used chemotherapeutic agent for the treatment of various cancers. Although it represents an effective regimen, its application is accompanied by side effects to normal tissues, especially to the kidneys. Cisplatin generates free radicals and impairs the function of antioxidant enzymes. Modulation of cisplatin-induced oxidative stress by specific antioxidant molecules represents an attractive approach to minimize side effects. Methods. We studied the ability of curcumin to sensitize leiomyosarcoma (LMS) cells to cisplatin. Assays for cell proliferation, mitochondrial function, induction of apoptosis, and cell cycle arrest were performed using various concentrations of cisplatin and a concentration of curcumin that caused a nonsignificant reduction in cell viability. Moreover, the effect of curcumin was examined against cisplatin-induced experimental nephrotoxicity. Renal injury was assessed by measuring serum creatinine, blood urea nitrogen (BUN), and the kidney’s relative weight. Oxidative stress was measured by means of enzymatic activities of superoxide dismutase and glutathione peroxidase in the rats’ blood and malondialdehyde levels in rats’ urine. Results. In our study, we found that curcumin sensitizes LMS cells to cisplatin by enhancing apoptosis and impairing mitochondrial function. In an in vivo model of cisplatin-induced experimental nephrotoxicity, intraperitoneal administration of curcumin failed to preserve blood’s antioxidant enzyme activity and decrease lipid peroxidation. Nevertheless, curcumin was able to protect nephrons’ histology from cisplatin’s toxic effect. Conclusion. Our results showed that curcumin can act as chemosensitizer, but its role as an adjunctive cisplatin-induced oxidative stress inhibitor requires further dose-finding studies to maximize the effectiveness of chemotherapy.

The importance and unique biological traits, as well as the growing financial value, of milk from small Greek ruminants is continuously attracting interest from both the scientific community and industry. In this regard the construction of a reference dataset of the milk of the Greek sheep breeds is of great interest. In order to obtain such a dataset we employed cutting-edge proteomics methodologies to investigate and characterize, the proteome of milk from the three indigenous Greek sheep breeds Mpoutsko, Karagouniko and Chios. In total, more than 1300 protein groups were identified in milk whey from these breeds, reporting for the first time the most detailed proteome dataset of this precious biological material. The present results are further discussed in the research paper “Milk of Greek sheep and goat breeds; characterization by means of proteomics” (Anagnostopoulos et al. 2016) [1].

Due to its rarity and unique biological traits, as well as its growing financial value, milk of dairy Greek small ruminants is continuously attracting interest from both the scientific community and industry. For the construction of the present dataset, cutting-edge proteomics methodologies were employed, in order to investigate and characterize, for the first time, the milk whey proteome from the two indigenous Greek goat breeds, Capra prisca and Skopelos. In total 822 protein groups were identified in milk whey of the two breeds, The present data are further discussed in the research article “Milk of Greek sheep and goat breeds; characterization by means of proteomics” [1]. Keywords: Foodomics, milk whey, Capra prisca breed, Skopelos Breed, LC-MS/MS, Greek goat

Over the past 30 years there has been a growing interest to unravel the dynamic framework of the milk proteome, and now that available technology is mature enough to enable techniques of protein fractionation and identification, this process is on-going. Due to its rarity and unique biological traits, as well as its growing financial value, milk of dairy Greek animals is continuously attracting interest from both the scientific community and industry. In the present study we employed cutting-edge proteomics methodologies to investigate and characterize, in depth, the proteome of whey from all pure-breed Greek sheep and goats. A mean of > 500 protein groups were identified in whey from each breed of each animal species, reporting for the first time the proteome dataset of this precious biological material. Given its high nutritional value, the protein properties exposed herein will govern future steps in optimizing characteristics and features of sheep and goat milk products. Significance In the present study we employed cutting-edge proteomics methodologies to investigate and characterize, in depth, the proteome of milk from all pure-breed Greek sheep and goats. A mean of > 500 protein groups were identified in milk whey from each breed of each animal species, reporting for the first time the proteome dataset of this precious biological material. Given its high nutritional value, the protein properties exposed herein will govern future steps in optimizing characteristics and features of sheep and goat milk products.

The aim of this study was to investigate the biological properties of goat milk from the indigenous Greek breed (Capra Prisca). The activity of the milk on platelet aggregation and thromboxane B2 production was evaluated on platelets isolated from blood obtained from both humans and rabbits. To further understand the biological properties of the milk ascorbic acid, linoleic and linolenic acid, were also tested. Ex vivo trials showed that milk from indigenous. Greek dairy goats (Capra Prisca) inhibited platelet aggregation at a dose dependent manner, both in humans and rabbits and decreased production of TXB2. The milk’s ability to inhibit platelet aggregation and reduce TXB2 production could be attributed to its high content in antioxidant substances and poly-unsaturated fatty acids (such as ascorbic acid and linolenic acid), when originating from grazing goats in semi-mountainous shrublands. The paper provides information for nutritionists and health professionals, about the biological properties of specific types of milk and their potential use as functional foods.

In the present study, genome-wide genotyping was applied to characterize the genetic diversity and population structure of three autochthonous Greek breeds: Boutsko, Karagouniko and Chios. Dairy sheep are among the most significant livestock species in Greece numbering approximately 9 million animals which are characterized by large phenotypic variation and reared under various farming systems. A total of 96 animals were genotyped with the Illumina's OvineSNP50K microarray beadchip, to study the population structure of the breeds and develop a specialized panel of single-nucleotide polymorphisms (SNPs), which could distinguish one breed from the others. Quality control on the dataset resulted in 46,125 SNPs, which were used to evaluate the genetic structure of the breeds. Population structure was assessed through principal component analysis (PCA) and admixture analysis, whereas inbreeding was estimated based on runs of homozygosity (ROHs) coefficients, genomic relationship matrix inbreeding coefficients (FGRM) and patterns of linkage disequilibrium (LD). Associations between SNPs and breeds were analyzed with different inheritance models, to identify SNPs that distinguish among the breeds. Results showed high levels of genetic heterogeneity in the three breeds. Genetic distances among breeds were modest, despite their different ancestries. Chios and Karagouniko breeds were more genetically related to each other compared to Boutsko. Analysis revealed 3802 candidate SNPs that can be used to identify two-breed crosses and purebred animals. The present study provides, for the first time, data on the genetic background of three Greek indigenous dairy sheep breeds as well as a specialized marker panel that can be applied for traceability purposes as well as targeted genetic improvement schemes and conservation programs.

Ruthenium η6-arene compounds of the general formula [(η6-arene)Ru(L)Cl](PF6), (1)PF6–(4)PF6, (η6-arene is benzene (bz) or p-cymene (cym), L is 2-(2′-pyridyl)quinoxaline (pqx) or 2-(2′-pyridyl)benzo [g]quinoxaline (pbqx)) and [(η6-cym)Ru(L)(9MeG)](PF6)2, (L is 2-(2′-pyridyl)quinoxaline (pqx), 2-(2′-pyridyl)benzo [g]quinoxaline (pbqx), 2,2′-bipyridine (bpy), 9MeG is 9-methylguanine), (5)(PF6)2–(7)(PF6)2, were synthesized and characterized by spectroscopic and analytical techniques. The molecular structures of the complexes (1)–(4), determined by single-crystal X-ray analysis of the hexafluorophospate salts, are also reported. In (5)(PF6)2–(7)(PF6)2, the nucleobase 9MeG binds to ruthenium through N7. Based on 1H NMR spectroscopy, a strong shielding effect between the aromatic ring system of the quinoxaline or benzo[g]quinoxaline moiety of the ligands pqx and pbqx and the H8 of 9MeG was observed. The complexes (1)–(4) are highly cytotoxic as chloride salts, against various cancer cell lines, with their IC50 values observed at less than 1 μΜ.

The homoleptic [Ru(trpyCO-TrpCONH2)2](PF6)2 (1), [Ru(trpyCO-Gly-TrpCONH2)2](PF6)2 (2) and the heteroleptic complexes [Ru(trpy)(trpyCO-TrpCONH2)](PF6)2 (3), [Ru(trpy)(trpyCO-Gly-TrpCONH2)](PF6)2 (4), where trpyCO-TrpCONH2 and trpyCO-Gly-TrpCONH2 are 2,2′:6′,2″-terpyridine-4-carboxylic acid-tryptophanamide and 2,2′:6′,2″-terpyridine-4-carboxylic acid-glycyl-tryptophanamide respectively, were synthesized and characterized by various spectroscopic and analytical techniques. The interactions of complexes (1) and (4) with the oligonucleotide d(5′-CGCGAATTCGCG-3′)2 were studied by means of NMR spectroscopy. Both complexes bound very weakly to the oligonucleotide, perturbing slightly the helix from B-form, probably through electrostatic interactions between the positive charge of the complexes and the DNA phosphates. In the case of complex (1), the conjugated tryptophane did not approach the oligonucleotide helix, as in the case of complex (4), the unsubstituted trpy of which was clearly orientated towards the oligonucleotide helix. These observations indicate that the bulky substitute on the ligand trpy reduces the binding affinity of the complexes to DNA, allowing only electrostatic interactions. However, complex (4) shows high cytotoxicity against LMS, MCF-7, U2OS and K562 cancer cell lines, with IC50 values ranging 0.464–0.925 μM, which can be attributed to a non classical mechanism for metal based anticancer agents.

The employment of pyridine-2-amidoxime (ampaoH), 2,6-diacetylpyridine dioxime (dapdoH 2 ) and pyridine-2,6-diamidoxime (dampdoH 2 ) in zinc(II) chemistry is reported. The syntheses, crystal structures, spectroscopic and physicochemical characterization, and biological evaluation are described of [Zn(O 2 CMe) 2 (ampaoH) 2 ] ( 1 ), [Zn(O 2 CPh) 2 (ampaoH) 2 ] ( 2 ), [Zn(dapdoH 2 ) 2 ](NO 3 ) 2 ( 3 ) and [Zn(dampdoH 2 ) 2 ](NO 3 ) 2 ( 4 ). The reactions between Zn(NO 3 ) 2 ·4H 2 O and two equivalents of either dapdoH 2 or dampdoH 2 in MeOH led to the mononuclear, cationic complexes 3 or 4 , respectively. The Zn II center in 3 and 4 is coordinated by two N , N ′, N ″-tridentate chelating ( η 3 ) dapdoH 2 or dampdoH 2 ligands, and it thus possesses a distorted octahedral coordination geometry. Strong intermolecular hydrogen bonding interactions provide appreciable thermodynamic stability and interesting supramolecular chemistry for compounds 1 – 4 . The characterization of all four complexes with 1 H and 13 C NMR, and positive ion electrospray mass spectroscopies confirmed their integrity in DMSO solutions. The biological evaluation of complex 3 showed the highest cytotoxic activity against LMS and MCF-7 cells, among the other three complexes ( 1 , 2 and 4 ). Flow cytometry analysis revealed that all four complexes cause apoptosis to LMS cells, at a dose-dependent manner. The combined work demonstrates the ability of pyridyl monoxime and pyridyl dioxime chelates not only to lead to polynuclear 3d-metal complexes with impressive structural motifs and interesting magnetic and optical properties, but also to yield new, mononuclear transition metal complexes with biological implications.

The missing VIV11VV7 oxidation-state member of the polyoxooctadecavanadate(IV/V) — azide family of inorganic host-guest systems has been incorporated in a NaI-containing 3D architecture; the complex shows remarkable inhibition properties on human platelet aggregation and antitumoural activity against cancer cell lines.

Chronic kidney disease is a condition that promotes oxidative stress. There are conflicting evidence about the role of hemodialysis on oxidative stress, that are mostly related with the various types of membrane materials used, the quality and type of dialysate, the method used, etc. The phase angle (PhA), which is determined with bioelectrical impedance analysis (BIA), measures the functionality of cell membranes. In this study, the correlation of the PhA with parameters of oxidative stress is attempted for the first time. We evaluated parameters of oxidative status as total antioxidant capacity (TAC) in erythrocytes (RBCs) and plasma of patients with ESRD undergoing hemodialysis with low flux synthetic polysulfone membranes. Measurements were recorded from 30 patients (16 men and 14 women) aged 64 ± 14 years before, during, and after dialysis, and in 15 healthy volunteers aged 56 ± 12 years The PhA was obtained by BIA. The plasma TAC increased significantly (41%, p

Since the initial success of cisplatin, metal complexes and organometallic compounds have been gaining growing interest in cancer therapy. It is well known that organotin(IV) compounds display strong biological activity. The triorganotin compound [(C(6)H(5))(3)Sn(cmbzt)] (cmbzt=5-chloro-2-mercaptobenzothiazole) (SnCMB), was tested for its antiproliferative and antitumour activities. Two sets of experimental procedures were followed: (1) In vitro and ex vivo procedures included the study of the cytotoxic activity of the complex against leiomyosarcoma cells (LMS) and on a normal human fibroblast line (MRC5) by the MTT assay (cell proliferation), colony formation efficiency and flow cytometric analysis with Annexin V-FITC. The anticoagulation properties of the complex were also studied. (2) In vivo procedures included acute toxicity studies and finally administration of the complex to tumour bearing Wistar rats. The results showed that the complex exhibited potent cytotoxic activity (LMS IC(50)=155 nM) and induced significant apoptosis against LMS cells. Acute toxicity studies on Wistar rats presented kidney and liver toxicity at a single dose of 40 mg/kg body wt. Furthermore, antitumour activity studies on sarcoma bearing Wistar rats revealed that SnCMB complex, administrated in two different therapeutic schemes (treated with 4 × 2 mg/kg body wt every 5 days and 3 × 2.67 mg/kg body wt every 10 days of SnCMB complex), prolonged mean survival time (by 50% and 70% respectively), but failed to decrease the mean tumour growth rate (MTGR) compared to the control group (p

Objectives The objective of this study was to investigate the effects of catechin and epicatechin on the activity of the endogenous antioxidant enzymes superoxide dismutase (SOD) and glutathione peroxidase (GPx) (as well as the total antioxidant capacity (TAC)) of rats after intra-peritoneal (i.p.) administration. Methods Twenty-four Wistar rats were randomly divided into two groups: the experimental group which was administered daily with a 1:1 mixture of epicatechin and catechin at a concentration of 23 mg/kg body weight for 10 days and the control group which was injected daily with an equal amount of saline. Blood and urine samples were collected before and after the administration period, as well as 10 days after (follow-up). Results Intra-peritoneal administration of catechins led to a potent decrease in GPx levels and a significant increase in SOD levels. TAC was significantly increased in plasma and urine. Malonaldehyde levels in urine remained stable. In the animals treated with catechins, SOD activity showed a moderate negative correlation with GPx activity. Discussion Boosting the activity of the antioxidant enzymes could be a potential adjuvant approach for the treatment of the oxidative stress-related diseases.

A study was conducted to evaluate the biological properties of milk from different animals and breeds such as cows, goats (Prisca, Ionica or Saanen breeds) and donkeys (Martina Franca breed). Methods included in vitro, ex vivo and in vivo experiments to evaluate the activity of milks on platelet aggregation and antioxidant capacity. The in vitro trials results demonstrated the highest total antioxidant capacity (TAC) in goats’ milk, especially from Prisca breed. Ex vivo trials showed that Prisca goats’ milk inhibits platelet aggregation at lower amounts than milk from other species. Consumption for 40 days of 0.6 L day −1 of Prisca goats’ milk significantly increased TAC in healthy volunteers. This study contributes to defining the biological properties of milk from these animals/breeds. Goats’ milk from the autochthonous Greek breed (Prisca) provided the best antioxidant capacity and inhibitory properties on platelet aggregation of the milk samples tested.

Nowadays, investigation for possible therapeutic applications of various metal-based drugs attracts the scientific interest worldwide. The triorganotin compound bis[triphenyltin(IV)](3-carboxy-pyridine-2-thionato) (SnMNA), was tested for its anti-proliferative and antitumor activities. Cytotoxic activity was assessed by Trypan blue and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay (MTT). SnMNA exhibited potent cytotoxic effects against leiomyosarcoma cells (LMS) and human breast adenocarcinoma cells (MCF-7), which is 200 times stronger than that of cisplatin. Moreover, SnMNA induced significant apoptosis in LMS and MCF-7 cells characterized by flow cytometry analysis and DNA fragmentation. Acute and chronic toxicity studies on Wistar rats caused kidney and lung toxicity at a single dose of 80 mg/kg Body Weight (BW) or four repeated doses of 8 mg/kg BW once per week. Furthermore, antitumor activity studies on sarcoma bearing Wistar rats revealed that SnMNA complex at four repeated doses of 5.4 mg/kg BW every three days prolonged mean survival time of the animal at 200% and decreased mean tumor growth rate (MTGR) compared to the control group (p < 0.05). It is noteworthy to mention that the 30% (3 out of 10) of the bearing animals were totally cured. These findings indicate that SnMNA might be a promising new antitumor agent. (C) 2010 Elsevier B.V. All rights reserved. European Journal of Pharmaceutical Sciences

The main catecholamine end-metabolites have been considered biologically inactive, but accumulated evidence indicates a variety of pharmacological actions after exogenous administration. We examined the dose-related haemodynamic effects of vanillylmandelic acid in the in vivo rat-model. One hundred and sixteen Wistar rats (250 ± 20 g) were studied under continuous electrocardiographic monitoring; invasive blood pressure was recorded for 60 min through a catheter in the right common carotid artery. Measurements were performed at baseline and after vanillylmandelic acid (1, 10, 100mg/kg) and homovanillic acid (10mg/kg) intra-arterial administration. To examine the underlying mechanisms, the haemodynamic effects were compared with those (a) after trimetazidine administration, which has similar structure due to a tri-methylated phenolic ring; (b) after epinephrine and isoprenaline administration following vanillylmandelic acid pretreatment; (c) after vanillylmandelic acid administration post-bilateral vagotomy. Vanillylmandelic acid, homovanillic acid and (to a lesser extent) trimetazidine decreased heart rate and mean arterial blood pressure. This effect was blunted in vagotomized animals. Comparable effects were noted in heart rate and blood pressure after adrenaline and isoprenaline infusion, with and without vanillylmandelic acid-pretreatment. In conclusion, vanillylmandelic acid administration decreases heart rate dose-dependently, mediated by increased vagal tone, without α- or β-adrenergic-receptor blocking effects. The pharmacological properties of compounds with a mono- and tri-methylated phenolic ring merit further investigation.

Exposure to various types of electromagnetic fields (EMFs) affects pain specificity (nociception) and pain inhibition (analgesia). Previous study of ours has shown that exposure to the resonant spectra derived from biologically active substances' NMR may induce to live targets the same effects as the substances themselves. The purpose of this study is to investigate the potential analgesic effect of the resonant EMFs derived from the NMR spectrum of morphine. Twenty five Wistar rats were divided into five groups: control group; intraperitoneal administration of morphine 10 mg/kg body wt; exposure of rats to resonant EMFs of morphine; exposure of rats to randomly selected non resonant EMFs; and intraperitoneal administration of naloxone and simultaneous exposure of rats to the resonant EMFs of morphine. Tail Flick and Hot Plate tests were performed for estimation of the latency time. Results showed that rats exposed to NMR spectrum of morphine induced a significant increase in latency time at time points (p 0.05), while exposure to the non resonant random EMFs exerted no effects. Additionally, naloxone administration inhibited the analgesic effects of the NMR spectrum of morphine. Our results indicate that exposure of rats to the resonant EMFs derived from the NMR spectrum of morphine may exert on animals similar analgesic effects to morphine itself.

Since the initial success of cisplatin, metal complexes and organometallic compounds have been gaining growing interest in cancer therapy. It is well known that organotin(IV) compounds display strong biological activity. The triorganotin compound [(C(6)H(5))(3)Sn(cmbzt)] (cmbzt=5-chloro-2-mercaptobenzothiazole) (SnCMB), was tested for its antiproliferative and antitumour activities. Two sets of experimental procedures were followed: (1) In vitro and ex vivo procedures included the study of the cytotoxic activity of the complex against leiomyosarcoma cells (LMS) and on a normal human fibroblast line (MRC5) by the MTT assay (cell proliferation), colony formation efficiency and flow cytometric analysis with Annexin V-FITC. The anticoagulation properties of the complex were also studied. (2) In vivo procedures included acute toxicity studies and finally administration of the complex to tumour bearing Wistar rats. The results showed that the complex exhibited potent cytotoxic activity (LMS IC(50)=155 nM) and induced significant apoptosis against LMS cells. Acute toxicity studies on Wistar rats presented kidney and liver toxicity at a single dose of 40 mg/kg body wt. Furthermore, antitumour activity studies on sarcoma bearing Wistar rats revealed that SnCMB complex, administrated in two different therapeutic schemes (treated with 4 × 2 mg/kg body wt every 5 days and 3 × 2.67 mg/kg body wt every 10 days of SnCMB complex), prolonged mean survival time (by 50% and 70% respectively), but failed to decrease the mean tumour growth rate (MTGR) compared to the control group (p0.01). In conclusion, the organic complex SnCMB possess potent cytotoxic and antimetastatic effects, and low toxicity introducing it as possible successor of organometallic compounds used nowadays in chemotherapy.

Ectopic pregnancy represents a rare pregnancy complication. In the last 20 years, with the use of IVF, heterotopic pregnancies have become more frequent, while this percentage differs between IVF programs. Many factors contribute to this, like the active management of hydrosalpinx or treatment of Chlamydia infection before starting a cycle. Although, in vitro fertilization is an expensive treatment, ectopic complication adds to this cost. Not a lot of studies exist for ectopic pregnancy after IVF. Most of them are case reports. Not a standard way exists, for dealing with heterotopic pregnancies, even in the era of modern laparoscopy. Not a lot of research has been performed on molecules that involved. Studies have tried to associate certain techniques during IVF, with this entity, but with controversial results. There is no standard form for diagnosing, dealing and presenting heterotopic pregnancies. Most of them are diagnosed when ruptured. Because it is rare event, costeffectiveness studies could not be performed and this complication is added to the overall IVF. Knowledge, on this field, is taken from the management of ectopic pregnancies in the general population, even if these present at a lower percentage. The purpose of the study is to systematically evaluate studies on molecular aspects of ectopic pregnancy, the ART techniques that are associated with ectopic pregnancy, the diagnosis of this entity and finally present case reports of heterotopic pregnancies and their management. At the end, cost-effectiveness models from the general population will be presented in parallel with systematic examination of these studies. Finally, new research targets will be pointed.

The main objective of our study is to investigate whether an enhancement of the immune system in end-stage cancer patients is achieved by exposure to coherent electromagnetic fields. For this reason, 15 end-stage cancer patients were exposed at low intensity, coherent electromagnetic fields at radiofrequencies ranging from 600 kHz--729 Hz, for 8 h/day, 6 days/week for 4 weeks. NKs number and cytotoxicity of NK T-lymphocytes versus K562 cancer cell line were estimated by flow cytometry, before and after exposure. Data showed that the exposure of the end-stage cancer patients to the coherent electromagnetic fields resulted in a significant increase of the number and the cytotoxicity of the NK T-lymphocytes against cancer cells, in all patients. Exposure to coherent EMFs at radiofrequencies increases the number and cytotoxicity of NK T-lymphocytes, which may contribute to the improvement of cancer patients' status.

Benign prostate hyperplasia (BPH) has been treated with various types of electromagnetic radiation methods such as transurethral needle ablation (TUNA), interstitial laser therapy (ILC), holmium laser resection (HoLRP). In the present study, the effects of a noninvasive method based on the exposure of patients with BPH to a pulsative EM Field at radiofrequencies have been investigated. Twenty patients with BPH, aging 68–78 years old (y.o), were enrolled in the study. Patients were randomly divided into two groups: the treatment group (10 patients, 74.0 ± 5.7 y.o) treated with the α-blocker Alfusosin, 10 mg/24 h for at least 4 weeks, and the electromagnetic group (10 patients, 73.7 ± 6.3 y.o) exposed for 2 weeks in a very short wave duration, pulsed electromagnetic field at radiofrequencies generated by an ion magnetic inductor, for 30 min daily, 5 consecutive days per week. Patients of both groups were evaluated before and after drug and EMF treatment by values of total PSA and prostatic PSA fraction, acid phosphate, U/S estimation of prostate volume and urine residue, urodynamic estimation of urine flow rate, and International Prostate Symptom Score (IPSS). There was a statistically significant decrease before and after treatment of IPSS (P

An overview of our work on the synthesis and biological activity of a series of tin(IV), silver(I) and antimony(III) complexes with thioamides is reported. Organotin(IV) complexes of formulae (n-Bu)2Sn(MBZT)2 (1), Me2Sn(CMBZT)2 (2), {(Ph3Sn)2(MNA) (Me2CO)} (3), Ph3Sn(MBZT) (4), Ph3Sn(MBZO) (5), Ph3Sn(CMBZT) (6), Ph2Sn(CMBZT)2 (7) and (n-Bu)2Sn(CMBZT)2 (8), Me2Sn(PMT)2 (9), (n-Bu)2Sn(PMT)2 (10), Ph2Sn(PMT)2 (11), Ph3Sn(PMT) (12) {where MBZT = 2-mercapto-benzothiazole, CMBZT = 5-chloro-2-mercapto-benzothiazole, H2MNA = 2-mercapto-nicotinic acid, MBZO = 2-mercapto-benzoxazole and PMTH = 2-mercapto-pyrimidine} were characterized by spectroscopic (NMR, IR, Mossbauer, etc.) and X-ray diffraction techniques and their influence on the peroxidation of oleic acid was studied. They were found to inhibit strongly the peroxidation of linoleic acid by the enzyme lipoxygenase. In addition, organotin(IV) complexes were found to exhibit stronger cytotoxic activity in vitro, against leiomyosarcoma cells, than cisplatin. The antiproliferative activity of the organotin complexes studied, against leiomyosarcoma cells follow the same order of LOX activity inhibition. This is, 3 ≫ 12 > 7 > 6 ≈ 8 ≈ 10 > 5 ≈ 4 ≫ 2 > 9. Thus, among organotin(IV)–CMBZT complexes, 7 exhibits higher activity than the others and this is explained by a free radical mechanism, as it is revealed by an EPR study. The results are compared with the corresponding ones found for the silver(I) complexes of formulae complexes {[Ag6(μ3-HMNA)4(μ3-MNA)2]2− · [(Et3NH)+]2 · (DMSO)2 · (H2O)} (13), {[Ag4Cl4(μ3-STHPMH2)4]n} (14), {[Ag6(μ2-Br)6(μ2-STHPMH2)4(μ3-STHPMH2)2]n} (15), {[Ag4(μ2STHPMH2)6](NO3)4}n (16), {[AgCl(TPTP)]4} (17), [AgX(TPTP)3] with X = Cl (18), Br (19), I (20) (where STHPMH2 = 2-mercapto-3,4,5,6-tetrahydro-pyrimidine, TPTP = tri(p-toly)phosphine) and those of antimony(III) complexes {[SbCl2(MBZIM)4]+ · Cl− · 2H2O · (CH3OH)} (21), {[SbCl2(MBZIM)4]+ · Cl− · 3H2O · (CH3CN)} (22), [SbCl3(MBZIM)2] (23), [SbCl3(EMBZIM)2] (24), [SbCl3(MTZD)2] (25), {[SbCl3(THPMT)2]} (26) and {[Sb(PMT)3] · 0.5(CH3OH)} (27) (where MBZIM is 2-mercapto-benzimidazole, EMBZIM = 5-ethoxy-2-mercapto-benzimidazole and MTZD is 2-mercapto-thiazolidine), which they have characterized with similar techniques as in case of organotin(IV) complexes. Silver(I) and antimony(III) complexes were found to be cytotoxic against various cancer cell lines.

An overview of our work on the synthesis and biological activity of a series of tin(IV), silver(I) and antimony(III) complexes with thioamides is reported. Organotin(IV) complexes of formulae (n-Bu)2Sn(MBZT)2 (1), Me2Sn(CMBZT)2 (2), {(Ph3Sn)2(MNA) (Me2CO)} (3), Ph3Sn(MBZT) (4), Ph3Sn(MBZO) (5), Ph3Sn(CMBZT) (6), Ph2Sn(CMBZT)2 (7) and (n-Bu)2Sn(CMBZT)2 (8), Me2Sn(PMT)2 (9), (n-Bu)2Sn(PMT)2 (10), Ph2Sn(PMT)2 (11), Ph3Sn(PMT) (12) {where MBZT = 2-mercapto-benzothiazole, CMBZT = 5-chloro-2-mercapto-benzothiazole, H2MNA = 2-mercapto-nicotinic acid, MBZO = 2-mercapto-benzoxazole and PMTH = 2-mercapto-pyrimidine} were characterized by spectroscopic (NMR, IR, Mossbauer, etc.) and X-ray diffraction techniques and their influence on the peroxidation of oleic acid was studied. They were found to inhibit strongly the peroxidation of linoleic acid by the enzyme lipoxygenase. In addition, organotin(IV) complexes were found to exhibit stronger cytotoxic activity in vitro, against leiomyosarcoma cells, than cisplatin. The antiproliferative activity of the organotin complexes studied, against leiomyosarcoma cells follow the same order of LOX activity inhibition. This is, 3 ≫ 12 > 7 > 6 ≈ 8 ≈ 10 > 5 ≈ 4 ≫ 2 > 9. Thus, among organotin(IV)–CMBZT complexes, 7 exhibits higher activity than the others and this is explained by a free radical mechanism, as it is revealed by an EPR study. The results are compared with the corresponding ones found for the silver(I) complexes of formulae complexes {[Ag6(μ3-HMNA)4(μ3-MNA)2]2− · [(Et3NH)+]2 · (DMSO)2 · (H2O)} (13), {[Ag4Cl4(μ3-STHPMH2)4]n} (14), {[Ag6(μ2-Br)6(μ2-STHPMH2)4(μ3-STHPMH2)2]n} (15), {[Ag4(μ2STHPMH2)6](NO3)4}n (16), {[AgCl(TPTP)]4} (17), [AgX(TPTP)3] with X = Cl (18), Br (19), I (20) (where STHPMH2 = 2-mercapto-3,4,5,6-tetrahydro-pyrimidine, TPTP = tri(p-toly)phosphine) and those of antimony(III) complexes {[SbCl2(MBZIM)4]+ · Cl− · 2H2O · (CH3OH)} (21), {[SbCl2(MBZIM)4]+ · Cl− · 3H2O · (CH3CN)} (22), [SbCl3(MBZIM)2] (23), [SbCl3(EMBZIM)2] (24), [SbCl3(MTZD)2] (25), {[SbCl3(THPMT)2]} (26) and {[Sb(PMT)3] · 0.5(CH3OH)} (27) (where MBZIM is 2-mercapto-benzimidazole, EMBZIM = 5-ethoxy-2-mercapto-benzimidazole and MTZD is 2-mercapto-thiazolidine), which they have characterized with similar techniques as in case of organotin(IV) complexes. Silver(I) and antimony(III) complexes were found to be cytotoxic against various cancer cell lines.

In the present study, the effects of a resonant low intensity static electromagnetic field (EMF), causing no thermal effects, on Wistar rats have been investigated. Sarcoma cell lines were isolated from leiomyosarcoma tumors induced in Wistar rats by the subcutaneous (s.c) injection of 3,4-benzopyrene. Furthermore, smooth muscle cells (SMC) were isolated from the aorta of Wistar rats and cultivated. Either leiomyosarcoma cells (LSC) or SMC were used to record a number of characteristic resonant radiofrequencies, in order to determine the specific electromagnetic fingerprint spectrum for each cell line. These spectra were used to compose an appropriate algorithm, which transforms the recorded radiofrequencies to emitted ones. The isolated LSC were cultured and then exposed to a resonant low intensity radiofrequency EMF (RF-EMF), at frequencies between 10 kHz to 120 kHz of the radiowave spectrum. The exposure lasted 45 consecutive minutes daily, for two consecutive days. Three months old female Wistar rats were inoculated with exposed and non-exposed to EMF LSC (4 x 10(6) LCS for animal). Inoculated with non-exposed to EMF cells animals were then randomly separated into three Groups. The first Group was sham exposed to the resonant EMF (control Group-CG), the second Group after the inoculation of LSC and appearance of a palpable tumor mass, was exposed to a non-resonant EMF radiation pattern, for 5 h per day till death of all animals (experimental control Group-ECG). The third Group of animals after inoculation of LSC and the appearance of a palpable tumor mass, was exposed to the resonant EMF radiation for 5 h per day, for a maximum of 60 days (experimental Group-I, EG-I). A fourth Group of animals was inoculated with LSC exposed to EMF irradiation and were not further exposed to irradiation (experimental Group-II, EG-II). Tumor induction was 100% in all Groups studied and all tumors were histologically identified as leiomyosarcomas. In the case of the EG-I, a number of tumors were completely regretted (final tumor induction: 66%). Both Groups of animals inoculated with exposed or non-exposed to the EMF LSC, (EG-I and EG-II, respectively) demonstrated a significant prolongation of the survival time and a lower tumor growth rate, in comparison to the control Group (CG) and the experimental control Group (ECG). However, the survival time of EG-I animals was found to be significantly longer and tumor growth rate significantly lower compared to EG-II animals. In conclusion, our results indicate a specific anticancer effect of resonant EMF irradiation. These results may possibly be attributed to (a) the duration of exposure of LSC and (b) the exposure of the entire animal to this irradiation.

In this study we investigated the effects of low intensity static radiofrequency electromagnetic field (EMF) causing no thermal effects, on leiomyosarcoma cells (LSC), isolated from tumors of fifteen Wistar rats induced via a 3,4-benzopyrene injection. Electromagnetic resonance frequencies measurements and exposure of cells to static EMF were performed by a device called multi channel dynamic exciter 100 V1 (MCDE). The LSC were exposed to electromagnetic resonance radiofrequencies (ERF) between 10 kHz to 120 kHz, for 45 min. During a 24h period, after the exposure of the LSC to ERF, there was no inhibition of cells proliferation. In contrast, at the end of a 48 h incubation period, LSC proliferation dramatically decreased by more than 98% (P0.001). At that time, the survived LSC were only 2% of the total cell population exposed to ERF, and under the same culture conditions showed significant decrease of proliferation. These cells were exposed once again to ERF for 45 min (totally 4 sessions of exposure, of 45 min duration each) and tested using a flow cytometer. Experiments as above were repeated five times. It was found that 45% of these double exposed to ERF, LSC (EMF cells) were apoptotic and only a small percentage 2%, underwent mitosis. In order to determinate their metastatic potential, these EMF cells were also counted and tested by an aggregometer for their ability to aggregate platelets and found to maintain this ability., since they showed no difference in platelet aggregation ability compared to the LSC not exposed to ERF (control cells). In conclusion, exposure of LSC to specific ERF, decreases their proliferation rate and induces cell apoptosis. Also, the LSC that survived after exposed to ERF, had a lower proliferation rate compared to the LSC controls (P0.05) but did not loose their potential for metastases (platelet aggregation ability). The non-malignant SMC were not affected by the EMF exposure (P0.4). The specific ERF generated from the MCDE electronic device, used in this study, is safe for humans and animals, according to the international safety standards.

There is growing evidence to show that administration of selenium (Se) is associated with a substantial reduction in the incidence and mortality of various cancer types such as skin, prostate, lung...

Lipid-lowering drugs have been developed to treat hyperlipidemia, but they are expensive, while serious side-effects may occasionally occur. In Albania, a hydroalcoholic extract of the cones of Cupressus sempervirens is used to treat a variety of disorders, including hyperlipidemia. The purpose of our study was to assess the effects of Cupressus sempervirens cone extract (CSE) on the lipid profile of Wistar rats.The animals were divided into two groups. Group I (30 animals) served as a control group. Serum lipid parameters, muscle and liver enzymes, red and white blood count, platelets, and serum concentrations of uric acid and creatinine were determined at baseline and at weeks 6, 12, 18 and 24 of the study.The oral administration of the extract resulted in a substantial decrease of serum total cholesterol, which was significant even after 6 weeks of treatment. Moreover, these animals exhibited lower total cholesterol levels compared to the controls after the initiation of treatment (p0.001) during the study period. The administration of the extract led to a substantial reduction in serum triglycerides (p0.05) in Group I, comparing 0 week to 6-24 weeks. However no significant differences in triglyceride levels were observed between CSE animals (Group I) and controls (Group II) during the entire study period. No significant changes in HDL-cholesterol in the other parameters occurred in either group.The administration of CSE has an important lipid-lowering effect in Wistar rats.

Objectives: To investigate the effectiveness of vitamin C and E supplementation in remission of the symptoms of chronic degenerative arthritis (osteoarthritis) of the knee. Design: A pilot controlled trial conducted from December 2009 until April 2011 among 46 patients diagnosed with osteoarthritis (OA) in one or both knees. Intervention: Patients were randomly assigned to two different treatment groups and were either supplemented with ascorbic acid 1 gr × 2 daily per os together with vitamin E 100 mg × 3 daily per os or they were treated with meloxicam tabs 15 mg × 1 daily per os. Main outcome measures: A. Clinical markers: functionality of the knee (WOMAC index), pain (using a pain visual analogue scale) and the deficit in knee flexion and extension B. Laboratory markers: total antioxidant capacity (TAC) and concentration of malonyldialdehyde (MDA) in the synovial fluid. Results: Twenty patients were randomly allocated into each of the two intervention groups. The treatment lasted for 20 days and the patients' status was evaluated every 10 days. The condition of the patients' knees in both treatment groups presented a significant improvement as recorded by the clinical markers; accompanied by an enhancement of TAC but with no effect on MDA levels. Conclusions: Administration of vitamins C and E has a similar effect in the remission of the symptoms of the OA in the knee, comparable to that of the treatment with meloxicam, but without the possible side effects and thus can be proposed as adjuvant therapy.

The reduction on peroxidation caused by benzopyrenes by some naturally occurring antineoplastic agents was studied in this experimental work. Inhibition/reduction of experimental carcinogenesis induced by benzo(a)pyrene by vitamin C alone and by vitamin C/vitamin E and selenium/ glutathione was attempted in 224 female Wistar rats divided in four groups. Injected with 10.08 mL benzo(a)pyrene, the animals were treated with some naturally occurring substances like vitamin C alone and a combination of anticarcinogens. By calculating the carcinogenic potency of benzo(a)pyrene and the anticarcinogenic potency of substances used as well as histological examination of developed tumors and survival time of treated animals, it was found that vitamin C exerts a significant anticarcinogenic effect of 8.3 units and that the combination of the two anticarcinogens used produced a significant prolongation of the animals survival time with anticarcinogenic potency of 22.1 and 22.2 units, respectively. This is considered a potent anticarcinogenic effect. The question of an additional supportive administration of such agents complementary to the conventional cancer chemotherapy in humans is raised. Of course, further studies are needed. Biol Trace Elem Res

The reactions of V(IV) sources and di-2-pyridyl ketone have led to V(IV)(2), V(V)(2) and V(V)(4) complexes with interesting structures and properties.