Invivo and invitro evaluation of antitumor effects of iron oxide and folate core shell-iron oxide nanoparticles / Avaliação in vivo e in vitro dos efeitos antitumorais de nanopartículas de óxido de ferro e óxido de ferro com núcleo de folato

Abstract Nanoparticles are considered viable options in the treatment of cancer. This study was conducted to investigate the effect of magnetite nanoparticles (MNPs) and magnetite folate core shell (MFCS) on leukemic and hepatocarcinoma cell cultures as well as their effect on the animal model of acute myelocytic leukemia (AML). Through current study nanoparticles were synthesized, characterized by various techniques, and their properties were studied to confirm their nanostructure. Invivo study, nanoparticles were evaluated to inspect their cytotoxic activity against SNU-182 (human hepatocellular carcinoma), K562 (human leukemia), and THLE2 (human normal epithelial liver) cells via MTT test. Apoptotic signaling proteins Bcl-2 and Caspase-3 expression were inspected through RT-PCR method. A cytotoxic effect of MNPs and MFCS was detected in previous cell cultures. Moreover, the apoptosis was identified through significant up-regulation of caspase-3, with Bcl-2 down-regulation. Invitro study, AML was induced in rats by N-methyl-N-nitrosourea followed by oral treatment with MNPS and MFCS. Biochemical indices such as aspartate and alanine amino transferases, and lactate dehydrogenase activities, uric acid, complete blood count, and Beta -2-microglubulin were assessed in serum. Immunophenotyping for CD34 and CD38 detection was performed. Liver, kidney, and bone marrow were microscopically examined. Bcl-2 promoter methylation, and mRNA levels were examined. Although, both MNPs and MFCS depict amelioration in biochemical parameters, MFCS alleviated them toward normal control. Anticancer activity of MNPs and MFCS was approved especially for AML. Whenever, administration of MFCS was more effective than MNPs. The present work is one of few studies used MFCS as anticancer agent.

Resumo Nanopartículas são consideradas opções viáveis ​​no tratamento do câncer. Este estudo foi conduzido para investigar o efeito de nanopartículas de magnetita (MNPs) e núcleo de folato de magnetita (MFCS) em culturas de células leucêmicas e de hepatocarcinoma, bem como seu efeito no modelo animal de leucemia mielocítica aguda (LMA). Através do atual estudo, nanopartículas foram sintetizadas, caracterizadas por várias técnicas, e suas propriedades foram estudadas para confirmar sua nanoestrutura. No estudo in vivo, as nanopartículas foram avaliadas para inspecionar sua atividade citotóxica contra células SNU-182 (carcinoma hepatocelular humano), K562 (leucemia humana) e THLE2 (fígado epitelial humano normal) por meio do teste MTT. A expressão das proteínas sinalizadoras apoptóticas Bcl-2 e Caspase-3 foram inspecionadas através do método RT-PCR. Um efeito citotóxico de MNPs e MFCS foi detectado em culturas de células anteriores. Além disso, a apoptose foi identificada por meio de regulação positiva significativa da Caspase-3, com regulação negativa de Bcl-2. No estudo in vitro, a AML foi induzida em ratos por N-metil-N-nitrosoureia seguida por tratamento oral com MNPS e MFCS. Índices bioquímicos como aspartato e alanina aminotransferases e atividades de lactato desidrogenase, ácido úrico, hemograma completo e Beta-2-microglubulina foram avaliados no soro. A imunofenotipagem para detecção de CD34 e CD38 foi realizada. Fígado, rim e medula óssea foram examinados microscopicamente. A metilação do promotor Bcl-2 e os níveis de mRNA foram examinados. Embora tanto os MNPs quanto os MFCS representem uma melhora nos parâmetros bioquímicos, o MFCS os aliviou em direção ao controle normal. A atividade anticâncer de MNPs e MFCS foi aprovada especialmente para AML. Sempre, a administração de MFCS foi mais eficaz do que MNPs. O presente trabalho é um dos poucos estudos que utilizou o MFCS como agente anticâncer.

Invivo and invitro evaluation of antitumor effects of iron oxide and folate core shell-iron oxide nanoparticles

Abstract Nanoparticles are considered viable options in the treatment of cancer. This study was conducted to investigate the effect of magnetite nanoparticles (MNPs) and magnetite folate core shell (MFCS) on leukemic and hepatocarcinoma cell cultures as well as their effect on the animal model of acute myelocytic leukemia (AML). Through current study nanoparticles were synthesized, characterized by various techniques, and their properties were studied to confirm their nanostructure. Invivo study, nanoparticles were evaluated to inspect their cytotoxic activity against SNU-182 (human hepatocellular carcinoma), K562 (human leukemia), and THLE2 (human normal epithelial liver) cells via MTT test. Apoptotic signaling proteins Bcl-2 and Caspase-3 expression were inspected through RT-PCR method. A cytotoxic effect of MNPs and MFCS was detected in previous cell cultures. Moreover, the apoptosis was identified through significant up-regulation of caspase-3, with Bcl-2 down-regulation. Invitro study, AML was induced in rats by N-methyl-N-nitrosourea followed by oral treatment with MNPS and MFCS. Biochemical indices such as aspartate and alanine amino transferases, and lactate dehydrogenase activities, uric acid, complete blood count, and Beta -2-microglubulin were assessed in serum. Immunophenotyping for CD34 and CD38 detection was performed. Liver, kidney, and bone marrow were microscopically examined. Bcl-2 promoter methylation, and mRNA levels were examined. Although, both MNPs and MFCS depict amelioration in biochemical parameters, MFCS alleviated them toward normal control. Anticancer activity of MNPs and MFCS was approved especially for AML. Whenever, administration of MFCS was more effective than MNPs. The present work is one of few studies used MFCS as anticancer agent.

Resumo Nanopartículas são consideradas opções viáveis no tratamento do câncer. Este estudo foi conduzido para investigar o efeito de nanopartículas de magnetita (MNPs) e núcleo de folato de magnetita (MFCS) em culturas de células leucêmicas e de hepatocarcinoma, bem como seu efeito no modelo animal de leucemia mielocítica aguda (LMA). Através do atual estudo, nanopartículas foram sintetizadas, caracterizadas por várias técnicas, e suas propriedades foram estudadas para confirmar sua nanoestrutura. No estudo in vivo, as nanopartículas foram avaliadas para inspecionar sua atividade citotóxica contra células SNU-182 (carcinoma hepatocelular humano), K562 (leucemia humana) e THLE2 (fígado epitelial humano normal) por meio do teste MTT. A expressão das proteínas sinalizadoras apoptóticas Bcl-2 e Caspase-3 foram inspecionadas através do método RT-PCR. Um efeito citotóxico de MNPs e MFCS foi detectado em culturas de células anteriores. Além disso, a apoptose foi identificada por meio de regulação positiva significativa da Caspase-3, com regulação negativa de Bcl-2. No estudo in vitro, a AML foi induzida em ratos por N-metil-N-nitrosoureia seguida por tratamento oral com MNPS e MFCS. Índices bioquímicos como aspartato e alanina aminotransferases e atividades de lactato desidrogenase, ácido úrico, hemograma completo e Beta-2-microglubulina foram avaliados no soro. A imunofenotipagem para detecção de CD34 e CD38 foi realizada. Fígado, rim e medula óssea foram examinados microscopicamente. A metilação do promotor Bcl-2 e os níveis de mRNA foram examinados. Embora tanto os MNPs quanto os MFCS representem uma melhora nos parâmetros bioquímicos, o MFCS os aliviou em direção ao controle normal. A atividade anticâncer de MNPs e MFCS foi aprovada especialmente para AML. Sempre, a administração de MFCS foi mais eficaz do que MNPs. O presente trabalho é um dos poucos estudos que utilizou o MFCS como agente anticâncer.

Amoxicillin–clavulanic acid induced sperm abnormalities and histopathological changes in mice

Objective To explore the genotoxic potential and histopathological changes induced in liver, kidney, testis, brain and heart after using the antibiotic drug amoxicillin/clavulanic acid (4:1). Methods The study included chromosomal aberration analysis in bone-marrow and mouse spermatocytes, induction of sperm morphological abnormalities and histopathological changes in different body organs. The drug was administrated orally at a dose of 81 mg/kg body weight twice daily (Total = 162 mg/kg/day) for various periods of time equivalent to 625 mg/men (twice daily). Results The results revealed non-significant chromosomal aberrations induced after treatment with amoxicillin/clavulanic acid (AC) in both bone marrow and mouse spermatocytes after 7 and 10 days treatment. On the other hand, statistically significant percentages of sperm morphological abnormalities were recorded. Such percentage reached 8.10 ± 0.55, 9.86 ± 0.63 and 12.12 ± 0.58 at the three time intervals tested (7, 14 and 35 days after the 1st treatment respectively) (treatment performed for 5 successive days) compared with 2.78 ± 0.48 for the control. The results also revealed histopathological changes in different body organs after AC treatment which increased with the prolongation of the period of therapy. Congestion of central vain, liver hemorrhage and hydropic changes in hepatocytes were noticed in the liver. Degenerative changes were found in kidney glomerulus and tubules while testis showed atrophy of seminiferous tubules, and reduction of spermatogenesis. AC also induced neurotoxicity and altered brain neurotransmitter levels. Hemorrhage in the myocardium, disruption of cardiac muscle fibers and pyknotic nuclei in cardiomyocytes were recorded as side effects of AC in heart tissue. Conclusions The results concluded that AC treatment induced sperm morphological abnormalities and histopathological changes in different body organs. Clinicians must be aware of such results while describing the drug.

microbiology of vaginal discharge and the prevalence of bacterial vaginosis in a cohort of non-pregnant women in Kuwait

To examine the microbiology of vaginal discharge and to estimate the prevalence of bacterial vaginosis and its association with sexually transmitted infections in a cohort of non-pregnant women in Kuwait. Retrospective study conducted during a six-month period [November 2009 - April 2010]. The gynecology outpatient clinic at the South Ardyia Health Unit, Farwania, Kuwait. Retrospective evaluation of medical records of 668 women, who attended the gynecology outpatient clinic at the South Ardyia Clinic, Farwania, Kuwait complaining of vaginal discharge during the study period. Retrospective review of the files for complaints, history, clinical examination and investigations of the vaginal discharge. A retrospective microbiological study of the infective etiology of vaginal discharge, the prevalence of bacterial vaginosis and its association with sexually transmitted infections. Microbiological causes of vaginal discharge accounted for 43.4% of cases. The commonest causes were bacterial vaginosis [prevalence = 18.9%] and candida infections [prevalence = 11.8%]. There was no significant association of bacterial vaginosis and sexually transmitted infections. Bacterial vaginosis is the commonest microbiological cause of vaginal discharge. Bacterial vaginosis is not a sexually transmitted disease

Evidence of enhanced trichodinids parasitic action in two Nile fish, oreochromis niloticus and clarias gariepinus, infected with gyrodactylids

Two different fish species [Oreochromis niloticus and Clarias gariepinus] were examined to investigate the correlation of parasitism between trichodinids and gyrodactylids. Four parasites were isolated from skin and gills of the examined fish: Trichodina centrostrigeata, [Basson et al. 1983, Trichodina compacta, Van As and Basson, 1989, Gyrodactylus rysavyi, Paperna, 1973 [28%] and Macrogyrodactylus clarii Gussive, 1961]. The highest prevalence [34.66%], intensity [23] and abundance [7.90] of parasitic infestation of C.gariepinus are shown in infected fish with gyrodactylids. A synergistic effect was noticed among such parasites studied herein. In field application, a special approach of such phenomenon [mixed infection] should be considered. In the present study, the clinical signs, prevalence, abundance of parasites and relative condition factor were reported and discussed

Clinical and surgical predictors of early post operative atrial fibrillation and sustained ventricular tachycardia after cardiac surgery

Post operative Atrial Fibrillation [AF]. Occurs up to 50% in cardiac surgery patients and represent the most common post operative complication. Although malignant ventricular tachycardia [V.T.] is uncommon arrhythmic complication early after cardiac surgery - it has a negative impact on mortality. The etiology of these arrhythmias [AF, V.T] after open heart surgery is incompletely understood and their prevention remains suboptimal. Identification of patients vulnerable for post operative [AF, V.T.] would allow targeting of these patients to benefit from aggressive prophylactic intervention. The aim of this work is to evaluate the incidence and identify risk factors of [AF, sustained V.T.] early postoperatively after cardiac surgery. 40 patients with a mean of age [55 +/- 10] years old [20 male, 20 female] under went isolated elective cardiac surgery [20 patients for valve replacement and 20 patients for CAPG]. Demographic and clinical data preoperative, operative and postoperative were collected. Patients continuously monitored and hemodynamically significant [AF, VT] were recorded. Detailed analysis was performed to define the risk factors. Post operatively AF occurred in [17/40] 42.5%. The mean age for patients with postoperative AF was 55 +/- 7.3 years old compared with 47.7 +/- 9.3 years old for patients without AF P<0.05. The mean heart rate variability [RMSSD] significantly differed between patients with post operative AF and patients without [15 +/- 2.1 msec VS 25 +/- 3 msec P<0.05]. The mean of P wave dispersion for patients with po AF was significantly prolonged compared to patients without AF [80 + 11 msec VS 42 +/- 12 msec, P<0.05]. Multivariate logesitic analysis [odds ratio +/- 95% CI, P value] was used to identify the following independent predictors of post operative AF: increasing age above VS below the mean age [OR = 2.8 CI [1.2-3.5] P<0.0] valve surgery VS CAPG [OR= 2.75 CI [1.2- 3.2] P<0.05], preoperative non use of beta blockers [OR= 1.5 CI [1.1-4.2] P<0.05] Considering several operative variables, use of internal mammary artery, pulmonary venting, cardiopulmonary bypass time, and aortic cross clamping time were significantly differed between the group with AF. And the group without AF. [26.6% VS 73.4% P=0.001] [71.4% versus 28.6% P=0.001], [113.8 +/- 33.5 m versus 92.4 +/- 36.3 m, P=0.002]. [97.8 +/- 21.5, versus 71.3 +/- 9.3, P = 0.001] respectively. Only one patient developed sustained VT post operatively [2.5%] of total study population, she was female had longer pump time than patient without sustained VT [120 min VS 80 +/- 9.5 min P<0.05]; longer Aortic cross clamping time [103 min VS 60 +/- 20 min P<0.05]; had increased QT[c]D than patient without sustained VT [120 msec VS 80 +/- 5 msec, P<0.05]. Patients with and without hemodynamically significant AF and sustained VT had similar body mass index preoperative heart rate and preoperative blood pressure. AF remains the most common complication after cardiac surgery. Increasing age and type of surgery identifies patients at risk for development of AF after cardiac surgery. Female sex, longer pump time, aortic cross clamping time, are independent predictors of developing sustanined VT post operatively. Increased QT[c] dispersion, decreased HRV, Root square of the mean of the sum of the Square of differences between adjacent R-R intervals [RMSSD] and increased PWD after cordic surgery may reflect disrupted electrophysiological stability of the myocardium and thus electrophysiological substrate for triggering malignant arrhythmias