Band 42, Heft 1

Objectives Vitamin D is very important for calcium and mineral metabolism, and many hypotheses appear to link sunlight exposure with cancer risk and prognosis. As many studies supported the antitumor effect of vitamin D we wanted to investigate the potential effect of multiple vitamin D metabolites. Methods This study compared the anticancer effect of three inactive forms of vitamin D 3 which are; cholecalciferol, alfacalcidol, and calcifediol on two human cancer cell lines colorectal cancer (CaCo II) and breast cancer (MCF-7). All were examined after 24, 48, and 72 h continuous exposure using a colorimetric assay (MTT) seeded in 96-multiwell plates. Doxorubicin anticancer used as a standard agent for comparison, while normal skin fibroblast cells (HDFa) was used as our negative control. IC 50 values were calculated as indication of antitumor effect. Results Broad-spectrum of cytotoxicity with IC 50 values ranging from 4 to 200 μM were found. Alfacalcidol was the most potent cytotoxic agents on colorectal cancer (CaCo II) and breast cancer (MCF-7) compared to cholecalciferol, and calcifediol. Both, alfacalcidol and calcifediol were more cytotoxic than cholecalciferol on the tested cell lines as they are partially active metabolites. Breast cancer (MCF-7) was the most sensitive to all metabolites at all-time intervals with the best IC 50 values of 4.35 μM ± 1.06 after 72 h continuous exposure of alfacalcidol. Conclusions Vitamin D metabolites are a potential option for cancer treatment along with or an alternative to chemo-therapeutics although extensive preclinical studies are required to prove this effect.

Objectives Fibroblast growth factor 19 (FGF-19) is a metabolic regulating factor with an anti-diabetic effect. This study aimed to evaluate FGF-19 in patients with type 2 diabetes mellitus (T2DM) and its relationship with some metabolic risk factors. Methods In this case-control study, 80 diabetic patients and 80 non-diabetic individuals were divided into two subgroups based on body mass index (BMI): obese people (BMI≥30) and participants with normal weight (25>BMI≥18.5). Furthermore, stratified analysis by gender was also performed. The metabolic factors were measured and compared in all groups. The relationship between FGF-19 and the measured items was investigated in each group. Results The FGF-19 levels did not show a significant difference between groups. The serum levels of FGF-19 were negatively associated with some metabolic items, such as BMI, low-density lipoprotein (LDL), total cholesterol (TC) (p<0.01), and LDL/high-density lipoprotein (HDL) ratio (p=0.02) only in the healthy group with normal weight. According to the gender-based classification of individuals, FGF-19 showed a significant inverse relationship with BMI, weight (WT), waist circumference (WC), and hip circumference (HC) (p<0.05) in diabetic men; besides, FGF-19 in non-diabetic women had a significant negative association with TC, LDL, and LDL/HDL ratio (p<0.05). Conclusions The levels of FGF-19 were negatively correlated to WT, BMI, WC and HC in diabetic males. More studies are needed to warrant these results.

Objectives Early-life stress (ELS) increases the risk of metabolic disorders in later life. The present study investigated the ELS effect on pancreatic pyruvate dehydrogenase (PDH) protein level, α-ketoglutarate dehydrogenase (α-KGDH), and aconitase activities as metabolic enzymes in response to young adulthood stress in male rat offspring. Methods Male Wistar rats were divided into six groups: Control, early life stress (Early STR), young adult foot-shock stress (Y. adult F-SH STR), early + young adult foot-shock stress (Early + Y. adult F-SH STR), young adult psychological stress (Y. adult Psy STR) and early + young adult psychological stress (Early + Y. adult Psy STR). Stress was induced by a communication box at 2 weeks of age and young adulthood for five consecutive days. The blood samples were collected in young adult rats, then pancreases were removed to measure its PDH protein level and aconitase and α-KGDH activities. Results In ELS animals, applying foot-shock stress in young adulthood increased PDH protein level, decreased α-KGDH and aconitase activities, and increased plasma glucose, insulin, and corticosterone concentrations. However, exposure to young adulthood psychological stress only decreased α-KGDH and aconitase activities. Conclusions It seems that ELS altered metabolic response to young adulthood stress through changes of Krebs cycle-related enzymes activities, though the type of adulthood stress was determinant.

Objectives Traffic noise, as one of the noise types, is a widespread feature of the urban environments. Traffic noise exposure can lead to hearing loss, hypertension, obesity and ischemic heart diseases. Thyroid hormones involved in the physiological and pathological conditions of the body. Therefore, this study was designed to aim the evaluation of traffic noise effects on thyroid hormones secretion and thyroid tissue structure. Methods Seventy two males and females wistar rats were used in this study. After one week adaptation, they divided randomly into 12 groups; the control, short term (one day) and long term (one, two, three and four weeks) groups. Traffic sound was recorded, adjusted and played (86 dB) for animals. Female rats’ cycle estrus was matched. At the end of experiment, the animals were anesthetized and cardiac blood sample was drawn. Thyroid tissue was then removed. Levels of the T3, T4, TSH, corticosterone and H&E staining were measured. p<0.05 considered to be statistically significant. Results Findings showed that in the one-day group, T3 levels increased and T3 levels decreased in the long term groups (p<0.05). In the same way, concentration of TSH decreased in the one day, while they increased in the one, two, three and four weeks’ groups (p<0.05). Histopathological evaluations showed that in the female and male animals, long-term traffic noise increased the full follicles and decreased empty follicles (p<0.05). Conclusions This study revealed that traffic noise exposure led to increase of T3 plasma concentration and decrement of TSH level, although in the long term, they return to basal status. It may be due to adaptation to traffic noise.

Objectives Thyroid hormones have important roles in normal development and energy regulating mechanisms as well as signaling mechanisms that affect energy consumption through central and peripheral pathways. The aim of this study was to determine the effects of thyroid dysfunction on adropin, asprosin and preptin levels in rat. Methods The study was performed on the 38 male Wistar-albino rats. Experiment groups were designed as follows. 1-Control, 2-Hypothyroidism; To induce hypothyroidism PTU was applied by intraperitoneal as 10 mg/kg/day for 2 weeks. 3-Hypothyroidism + Thyroxine; Previously animals were made with hypothyroidism by 1 week PTU application and then 1 week l -thyroxine was given by intraperitoneal as 1.5 mg/kg/day. 4-Hyperthyroidism; Rats were made with hyperthyroidism by 3 weeks l -thyroxine (0.3 mg/kg/day). 5-Hyperthyroidism + PTU; Animals were made hyperthyroisim by l -thyroxine as groups 4, then 1 week PTU was applied to treatment of hiperthyrodism. At the end of supplementation animals were sacrificed and blood samples were collected for FT3, FT4, adropin, asprosin, preptin analysis. Results FT3 ve FT4 levels were reduced significantly in hypothyroidism while increased in hyperthyroidism (p<0.001). Hipothyrodism led to reduces adropin, asprosin and preptin levels. And also hyperthyroidism reduced adropin and preptin levels (p<0.001). Conclusions The results of study show that experimental hypothyroidism and hyperthyroidism lead to significantly change to adropin, asprosin and preptin levels. However, correction of thyroid function caused to normals levels in asprosin and preptin.

Objectives Nanoparticles have special properties, such as increased intestinal absorption, permeability, and so on. Zinc oxide (ZnO) nanoparticles have medical applications such as using in drug production. Studies of ZnO nanoparticles have shown the role of these particles in reducing or increasing the genes expression. Given the important role of hepcidin in the development of anemia and iron overload diseases, this study investigated the effect of ZnO nanoparticles on the hepatic expression of the hepcidin gene to help find a way to treat these diseases. Methods In this experimental study, 24 male Westar rats were divided into three groups: control, ZnO treating group and ZnO nanoparticle treating group. Both ZnO and ZnO nanoparticles were injected with 50 mg/kg body weight for 14 days. At the end, serums were collected and iron, ferritin and IL-6 levels were measured. Expression of the hepcidin gene was done by Real Time PCR. Results ZnO and the ZnO nanoparticle significantly increased the expression of the hepcidin gene relative to the control group. The increase in expression of the hepcidin gene in ZnO nanoparticles was more significant than in the ZnO. Conclusion ZnO nanoparticles led to significant increase in expression of the hepcidin gene.

Objectives To compare the effect of Iberet Folic ® and Zincofer ® on haemoglobin (Hb) and serum ferritin level; and its adverse effect. Methods This randomised controlled trial conducted from January 2018 until December 2018. Pregnant women below 34 weeks of gestation, with Hb concentration less than 11 g/dL and serum ferritin level less than 12 ug/L were randomised to receive either one tablet Zincofer ® or one tablet Iberet Folate ® daily for four weeks. Both groups were compared in terms of effect on Hb level, serum ferritin level, and other haematological indices adverse effect related to treatment, and treatment cost. Results Hundred and thirty patients were recruited in this study with 68 patients in Iberet Folic group and 62 patients in Zincofer group. The change in the Hb and serum ferritin level from baseline to day 30 did not differ significantly between treatment groups. The mean (±SD) change from baseline to day 30 was 2.15 (±0.59) g/dL in the Iberet Folic group, and 1.98 (±0.49) in the Zincofer (p value = 0.08). Mean serum ferritin at day 30 was 17.2 (±3.68) ug/L and 16.7 (±4.28) ug/L with 8.44 (±3.41) and 8.55 (±3.50) difference, respectively (p = 0.86). Adverse events were comparable in between groups, with p value >0.05. GI intolerance and constipation were among the common side effects, occurred in 34.6 and 29.2% cases, respectively. Conclusions Zincofer ® offers equivalent efficacy and side effect profile in comparison with Iberet Folic ® for the treatment of iron deficiency anaemia (IDA) during pregnancy, but with lower cost.

Objectives Novel coronavirus disease (COVID-19) is rapidly spreading all over the world. Although in many cases the infection causes very weak symptoms, it can be severe in patient with diverse chronical diseases and immunological compromising patients. Pregnancy is a unique condition in which mother and fetus peacefully collaborate. Diverse endocrine-immune mechanisms, mostly under progesterone control work together to protect the fetus from maternal immunocompetent cell activation driven rejection. The physiological shift to Th2 dominant environment, while favourable for fetus, it makes mothers susceptible to infective pathogens, making pregnancy during COVID-19 pandemic challenging. Materials and methods Studies involving COVID-19 in pregnancy and those analysing changes of immune system induced by COVID-19 were searched in databases such as PubMed, Scopus, Google Scholar and ScienceDirect. Databases were searched using a keyword COVID-19/coronavirus, that was combined with following terms: immune system, pregnancy, oestrogen, or progesterone. Search included studies published up to 01.07.2020. Almost 1,500 articles were found, but only 18 met criteria. Results Most frequent symptoms of COVID-19 in mothers infected in the late pregnancy were fever and cough accompanied with lymphopenia and elevated C-reactive protein. Mothers reported to have severe disease had comorbidities and were obese. Low rate of neonatal complications of maternal Sars-Coc-2 infection without neonatal mortality was observed. Conclusions Currently available data didn’t show significant relationship between COVID-19 severity and pregnancy and there is no strong evidence that mother’s infection can lead to adverse pregnancy outcome, but further studies are needed to determinate the possible effects of COVID-19 gained during earlier pregnancy.

After the global outbreak of coronaviruses caused diseases such as Middle East Respiratory Syndrome (MERS) and Severe Acute Respiratory Syndrome (SARS), an outbreak due to these viruses occurred in December, 2019 in Wuhan, Hubei Province, China and led to a worldwide spread. Coronavirus 2019 disease (COVID-19) has emerged as a serious global health emergency and spread from a person to another who has the virus. But the scope of an intermediate host is not known. Population at higher risk includes individuals in higher age group (>60 years) or with comorbidities such as diabetes, hypertension, cardiovascular disease and weaker immune system. Many unknown and underestimate risk factors could be responsible for adverse outcomes in COVID-19. These risk factors should be appropriately identified, addressed and necessary actions should be taken to mitigate the effect of COVID-19 pandemic. Bhopal gas tragedy was one of the world’s worst industrial chemical leak disaster. The survivors of this incident still suffer from the various complications such as increased rate of cancers, chronic illness like tuberculosis, respiratory diseases, birth defects, nerve injury, growth retardations, gynecological illness and many more. The survivors of Bhopal gas tragedy are at higher risk of developing COVID-19 related adverse outcome. One of the possible explanations can be long term effect of methyl isocyanate (MIC). MIC exposure can lead to possible toxic effect on genetic, epigenetic and non-genetic factors. In this review, we aim to establish the scientific basis for adverse outcome in COVID-19 patients who are also victims of Bhopal gas tragedy.

COVID-19 caused by SARS CoV2 (The novel corona virus) has already taken lives of many people across the globe even more than anyone could have imagined. This outbreak occurred in China and since then it is expanding its devastating effects by leaps and bounds. Initially it appeared to be an outbreak of pneumonia but soon it was found to be much more than that and the infectivity was found to be very high. This is the reason that it has taken whole globe in its trap and become a pandemic in such a short span of time. Death is occurring because it is a new virus and human body has no specific antibodies for it. Presently there is no approved vaccine so everyone is susceptible but people with co-morbidities appear to be in more risk and the best way for protection is social distancing and increasing one’s natural immunity by taking healthy diet and exercise. When a person is infected the clinical presentation ranges from asymptomatic to severe ARDS, sudden onset of anosmia, headache, cough may be the initial symptoms. This review is focused on immunopathology and effect of COVID-19 on neurological disorders and also the neurological manifestations and the treatment.

COVID-19 has resulted in an ongoing global pandemic, which spread largely among people who have had close contact with the infected person. The immunopathology of the SARS-CoV-2 virus includes the production of an excess amount of pro-inflammatory cytokines “a cytokine-storm”. The respiratory system (main), cardiovascular system and the gastrointestinal tract are the most affected body systems during viral infection. It has been found that most of the patients who require admission to hospital are elderly or have chronic underlying diseases. Higher cases of malnutrition and co-morbidities like diabetes mellitus and cardiovascular diseases are reported in elderly patients due to which, the immune system weakens and hence, the response to the virus is diminished in magnitude. A deficiency of micronutrients results in impaired immune responses leading to improper secretion of cytokines, alterations in secretory antibody response and antibody affinity which increases susceptibility to viral infection. The deficiency of various micronutrients in COVID-19 patient can be treated by appropriate nutritional supplements, prescribed after evaluating the patients’ nutritional status. Here we aim to highlight the role of a few particular nutrients namely Vitamin D, Vitamin C, Omega-3 fatty acids, Zinc and Magnesium along with the synergistic roles they play in enhancing immunity and thus, maintaining homeostasis.

The COVID-19 pandemic has not only led to a worldwide socio-economic depression, but has also had the highest health impact on the geriatric population. Elderly population, due to various reasons such as low immunity, pre-existing co-morbidities such as hypertension, cardiovascular diseases or diabetes, are obviously predisposed to develop severe infections and exhibit a high mortality rate. This is because of many reasons which include the atypical presentation in the geriatric population which might have led to diagnostic delay. As per the WHO guidelines to perform RT-PCR only on the symptomatic individuals, a very small portion of individuals were tested, leaving a fraction of population undiagnosed. Therefore, there remained a chance that many asymptomatic individuals such caregivers, healthcare professionals, family members were undiagnosed and might have carried this virus to the geriatric patients. Also, many countries were not prepared to handle the burden on their healthcare system which included sudden increased demand of ICU beds, mechanical ventilation etc. As a result, they had to make decision on who to be admitted. Atypical presentation in geriatric population may include afebrile or low-grade fever, absence of cough, malaise, muscle pains, dyspnoea etc. Geriatric population shows a more severe type of pneumonia, significantly higher number of neutrophils and C-reactive protein, less lymphocytes and a higher proportion of multiple lobe involvement. Extreme social suppression during COVID-19 pandemic has increased the risk of mental and physical adverse effects that has made older adults more vulnerable to depression and anxiety.

The uncontrolled spread of the COVID-19 pandemic which originated in China created a global turmoil. While the world is still busy figuring out a cure for the deadly disease, scientists worked out on many theories and conducted several studies to establish a relationship between the infection and other known diseases. Cardiovascular diseases (CVD) are one of the major complications of this infection after the respiratory manifestations. Individuals with cardiovascular complication are said to be more susceptible to acquiring the infection because the novel coronavirus uses the ACE2 receptor for its entry inside the cell and there is a high level of ACE2 expression in individuals with cardiovascular complications because of the enzyme’s anti-hypertrophic, anti-fibrotic and anti-hypertensive effects on the heart. Individuals who belong to the older age group are also more susceptible. Knowing the above information, it might seem that using ACE2 inhibitors would help to slow or prevent the entry of the novel coronavirus but it would also at the same time prove to have deleterious effects on the cardiovascular system as the protective functions of ACE2 would be lost. While the search for a cure still continues it has been stated many a times that the conditions might worsen with time and the only way to keep ourselves and our family safe would be to follow the appropriate social distancing methods and get a COVID test if we experience any of the major symptoms.

The aim of this study is to evaluate and compare outcomes of patients with mixed and pure endometrial carcinomas (MEC). We reviewed data of patients with MEC, endometroid (EC), serous (SC), and clear cell (CC) carcinomas between 2002 and 2015. Overall survival (OS) and disease-free (DF) survival rates were evaluated, according to the percentage of histologic components. Clinicopathological variables and treatment strategies were assessed. Furthermore, χ 2 tests were used to compare proportions and Kaplan–Meier curves to compare recurrence and survival. Sample consisted of 302 cases with mean age 66.3 years. Early-stage disease was recorded in EC compared with CC and SC. Adnexal involvement was more frequent in MEC compared with EC (p=0.043). Extra uterine metastasis was more frequent in the SC compared to the EC group, while lymphovascular space involvement was more frequent in the MEC and CC compared to the SC (p=0.001). EC had less omentum involvement compared to CC (p=0.035) and SC (p<0.001). Furthermore, cervical involvement was more frequent in CC compared to EC (p=0.011). Recurrence (p=0.265) and OS (p=0.533) were found to be similar in MEC compared with CC, SC, and EC. Moreover, recurrence and OS were similar between EC-CC and EC-SC. There were no differences in recurrence and survival in MEC with a type II component larger than 10% or 20% (p>0.05).