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Alterations of The Stem-Like Properties in The Breast Cancer Cell Line MDA-MB-231 Induced by Single Pulsed Doxorubicin Treatment

Abstract

Development of chemoresistance remains a significant limitation for the treatment of cancer and contributes to recurrence of the disease. Both intrinsic and acquired mechanisms of chemoresistance are characteristics of cancer stem cells (CSCs) or stem-like cells (SLCs). The aim of the study was to assess the stem-like properties in the breast cancer cell line MDA-MB-231 during and after pulsed treatment with doxorubicin (DOX) in comparison to the untreated controls.The experimental cultures were exposed to therapeutic concentration of DOX for 48 hours (treatment cultures), and subcultured to post-treatment cultures 24 hours after the removal of DOX. Stem-like properties of the cellular populations in the treatment and post--treatment cultures were assessed by the expression of the stem-cell marker genes (CD24, CD44, ITGA6, ITGB1, POU5F1, NANOG, ALDH1A1), colony-formation efficiency, growth rates, and sensitivity to DOX, 5-fluorouracil (5FU), cisplatin (CIS), and vinblastine (VBL). Exposure to DOX induced formation of giant polyploid cells that persisted in the post-treatment culture. The recovery period was characterised by a decrease in the proliferation rate, viability, and cellular adherence. The post-treatment cultures displayed decreased sensitivity to DOX and increased sensitivities to 5FU, CIS, and VBL. Cells treated with DOX displayed increased expression levels of CD24, CD44, and ALDH1A, while their expression levels at least partially normalised in the post-treatment culture. The post-treatment cultures demonstrated significantly increased colony-formation ability. During treatment with sub-lethal levels of doxorubicin and during the acute recovery period, the survival mechanisms in the breast cancer cell line MDA-MB-231 may be mediated by formation of the cellular population with stem-like properties.

Open access
Biomechanical Properties of Human Dilated Ascending Aorta

Abstract

Aneurysms of ascending aorta are dilatation of the first part of the human aorta. They commonly show no clinical symptoms. This condition increases the risk of aorta dissection, which is a life-threatening condition. In this study we attempted to elucidate the changes in the biomechanical properties that occur in the dilated human ascending aorta. Fourteen specimens of ascending aorta wall were mechanically tested under a uniaxial tensile test. Two specimens from each ascending aorta anterior region were cut in longitudinal and circumferential directions. The samples were stretched until rupture of the sample occurred. The obtained experimental data were processed to determine maximal stress, maximal strain and the tangential modulus of elasticity in the linear part of the stress-strain curve. The obtained results showed a remarkable anisotropy of the ascending aorta tissue. We found higher strength of the tissue in the circumferential direction than in the longitudinal direction. There were no statistically significant differences between the strains of the samples. Tangential modulus of elasticity of the aortic samples in the longitudinal direction was significantly lower than the elastic modulus of the samples in the circumferential direction. The tissue in the circumferential direction is stronger and stiffer than in the longitudinal direction.

Open access
Changes in Diagnostic Patterns of Depression Among Family Physicians in Latvia after Participating in The Education Course on Depression Developed within the National Research Programme Biomedicine 2014–2017: Preliminary Results

Abstract

Annually, 7.9% of the general population in Latvia are suffering from depression. According to the official statistics, less than 8000 persons a year have been treated for depression in the state-paid health care services while the National Research Programme (NRP) BIOMEDICINE 2014–2017 found that more than 70 000 depressed patients annually are coming to family physicians (FPs) in Latvia. Within NRP researchers have developed an algorithm for diagnostics and treatment of depression and carried out ten educational courses for FPs all over Latvia in 2016. Data on the treatment of depression have been collected from the National Health Service (NHS) database from 01.01.2015 till 30.06.2017. Changes between the trained and control groups have been calculated for the time period before intervention — 2015–2016 and six months right after it. The “Depression School” was attended by 210 (15.2%) out of 1382 FPs, in contract with the NHS, who signed in for the course on first-to-come basis. There were no statistically significant demographic differences between trained and control groups, except, a larger proportion of FPs from rural places vs. the capital city attended the courses. Comparing the trained and control groups, during the period before the intervention there were on average 0.96 vs. 0.83 depressive episodes (F32) and 3.26 vs.1.74 recurrent depressive disorder (F33) episodes in 1/2 year (p < 0.001). Statistically significant increase was observed for F33 episodes (+1.42, p < 0.001), and numeric for F32 episodes (+0.18, p = 0.36) in the trained group of FPs in 2017. In total this gave a statistically significant (p < 0.001) increase by 43.6% of F33 diagnoses following the education course on depression for family physicians. Further analysis of data to access sustainability of training effect after 12 and 24 months are underway.

Open access
Coping with Febrile Illness in Children: A Qualitative Interview Study of Parents

Abstract

The aim of this study was to investigate parental perception of febrile illness in their children, the most commonly applied management practices, as well as the expectations from clinicians when coping with fever in children. The study included parents of patients admitted to the Emergency and Observation Department of Children’s Clinical University Hospital in Rīga, Latvia. Data were collected via semi-structured interviews. All interviews were transcribed, and the transcripts analysed by inductive thematic analysis. Thirty-four parental interviews were analysed. Six themes emerged from the study, which were: signs causing concern; beliefs regarding fever; assessment and monitoring of fever; fever management practices; help-seeking behaviour; and expectations from the healthcare personnel. Many parents believed that fever could potentially cause injuries to the nervous system, kidneys, the brain, other internal organs, and even cause death. The perceived threat of fever resulted in frequent temperature measurements and administration of antipyretics. Meeting the emotional and information needs of the parents were considered as equally important to meeting the child’s medical needs. The study found that fever phobia exists among parents. Parental misconceptions of fever lead to overly zealous management practices. Parental education initiatives must be organised in order to improve parental knowledge of fever and its management in children.

Open access
Diagnostics and Treatment of Neonatal Necrotising Enterocolitis in Latvia

Abstract

Necrotising enterocolitis (NEC) is one of the leading causes of neonatal morbidity, mortality and surgical emergencies. As the survival rate of extremely low birth weight (ELBW) infants is rising, so is the risk of NEC. The aim of this study was to compare diagnostics parameters like clinical and radiological findings and laboratory indicators and the treatment and outcome of NEC patients from 2000 till 2007 (Group 1) and from 2008 till 2016 (Group 2) treated in Neonatology Clinic (NC) of Children’s Clinical University Hospital (CCUH). In the rectrospective study, 277 newborns were divided among Group I and Group II – 105 and 172 patients, respectively. There were no statistically significant differences between both study groups in mean gestational age and birth weight. In both groups the first signs of NEC appeared on average eight days after birth. Differences in the diagnostic method used in both groups were not statistically significant; specific radiological findings were seen in approximately 1/3 of the cases. There were statistically significant differences in the management of NEC and patient mortality. Conservative therapy was applied in 70.0% of patients in both study groups. Over time, peritoneal drainage (PPD) as the sole surgical treatment decreased by 6.4%, but PPD with following enterostomy decreased by 8.9%. In Group 2 mortality of NEC patients decreased by 17.4%. Mortality among surgically treated NEC patients decreased as well, by 9.0%.

Open access
Differences in Long- and Short-Term Memory Performance and Brain Matter Integrity in Seniors With Different Physical Activity Experience

Abstract

Due to increasing changes in demographics, maintaining cognitive functioning later in life has become both economic and social concerns, and thus finding a cost-effective solution is one of the priorities in research. Factors like physical and intellectual activities have been associated with better cognitive performance in later life. While several studies have considered the impact of short-term physical activity interventions on cognitive functioning, retrospective research focusing on life-time physical activity experience has been sparse. The aim of the study was to determine the relationship between memory performance and whole brain matter integrity in seniors with different regular life-long physical activity experience. Fifty-three Latvian seniors aged 65–85 (M = 72.25, SD = 5.03, 83% female) with no self-reported chronic disease participated in the study. Measures of memory, physical activity and whole brain matter integrity were obtained and analysed. The obtained results indicated no significant relationship between physical activity experience and short and long-term memory and whole brain matter integrity; however, brain matter integrity was significantly correlated with demographic factors like age and education. These results might be related to inadequate physical activity measures, as well as unequal physical activity experience in participants. In the future, more detailed assessment of physical activity experience should be considered.

Open access
General Influence of Biphasic Calcium Phosphate on Osteoporotic Bone Density

Abstract

Bone density of the femur body of rabbit was determined in vivo. Experimental osteoporosis was induced by ovariectomy and subsequent injections of methylprednisolone. In the greater trochanter region of right femur, defects were created and filled with granules of hydroxyapatite and tricalcium phosphate (HAP/TCP 70/30) or HAP/TCP 70/30 together with 5% strontium. After three months, the animals were euthanized. The bone mass density of the right and left body of femur was measured by cone beam computed tomography (CT) scan. The results of the study showed that the right femur of the rabbit, where biomaterials had been implanted, and the left femur, where no biomaterial implantation occurred, became denser after filling the defect with HAP/TCP 70/30 ceramic granules or 5% Sr modified HAP/TCP ceramic granules. There was no difference between operated and non-operated legs and HAP/TCP and HAP/TCP with 5% strontium groups.

Open access
Human Leukocyte Antigens Class II Alleles Affecting the Response to 5–7 Year Antiretroviral Therapy in A Latvian Cohort

Abstract

Antiretroviral therapy (ART) aims at suppressing viral replication and strengthening immune system in patients with HIV-1. Human Leukocyte Antigens (HLA) are among factors responsible for effectiveness of ART. The aim of this study was to determine the effect of HLA Class II alleles on the response to long-time ART, assessed by a change in CD4+ T-cell count in relation to viral load. The sample included 69 patients (17 females and 52 males) aged 20 to 50 with HIV-1 infection, who were undergoing ART in the Latvian Centre of Infectious Diseases. The median period of observation was 5.7 years. CD4+ T-cell count and viral load were analysed at the baseline and end of the period of observation. HLA typing was performed by polymerase chain reaction with low resolution sequence specific primers. Multiple hierarchical linear regression analysis confirmed that an increase in HIV-1 viral load was associated with a decrease in the level of CD4+ T-cell count. In addition, HLA-DRB1*04 and HLA-DQB1*06:01 alleles contributed negatively to the level of CD4+ T-cell count.

Open access
Immunological Mechanisms of Autoimmune Thyroid Diseases: A Shift in The Traditional TH1/TH2 Paradigm

Abstract

Autoimmune thyroid diseases (AITD) mainly include Hashimoto’s thyroiditis (HT) and Graves’ disease (GD), which are characterised by the presence of circulating antibodies against various thyroid autoantigens and infiltration of the thyroid gland by autoreactive lymphocytes. Despite the significant advancement in the knowledge of AITD pathogenesis in the last decade, the specific immunological mechanisms responsible for development of the disease are not thoroughly understood. Classically, HT has long been considered as a T helper (Th)1-mediated disease, while a Th2-driven autoimmune response is dominant for GD development. However, this classification has changed due to the description of Th17 lymphocytes, which suggested participation of these cells in AITD, particularly HT pathogenesis. Moreover, a shift in the balance between Th17 and T regulatory (Treg) cells has been observed in thyroid autoimmunity. We have observed overexpression of IL-17, the prominent effector cytokine of Th17, within thyroid tissues from HT and GD patients in our studies. The present review will focus on recent data regarding the role of Treg and Th17 lymphocytes in AITD pathogenesis. In addition, the impact and proposed mechanisms of the predominant environmental factors triggering the autoimmune response to the thyroid will be discussed.

Open access