Metabolic dysregulation in obese women and the carcinogenesis of gynecological tumors: A review.

Obesity is a significant health issue associated with increased cancer risks, including gynecological malignancies. The worldwide rise in obesity rates is significantly impacting both cancer development and treatment outcomes. Adipose tissue plays a crucial role in metabolism, secreting various substances that can influence cancer formation. In obese individuals, dysfunctional adipose tissue can contribute to cancer development through inflammation, insulin resistance, hormonal changes, and abnormal cholesterol metabolism. Studies have shown a strong correlation between obesity and gynecological cancers, particularly endometrial and breast cancers. Obesity not only increases the risk of developing these cancers but is also associated with poorer outcomes. Additionally, obesity affects the perioperative management of gynecological cancers, requiring specialized care due to increased complications and resistance to therapy. Treatment strategies for managing metabolic dysregulation in patients with gynecological cancers include weight management, statin therapy, and insulin-sensitizing medications. Emerging studies suggest that interventions like intermittent fasting and caloric restriction may enhance the effectiveness of cancer treatments. Furthermore, targeting cholesterol metabolism, such as with statins or proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors, shows potential in cancer therapy. In conclusion, addressing metabolic issues, particularly obesity, is crucial in preventing and treating gynecological malignancies. Personalized approaches focusing on weight management and metabolic reprogramming may improve outcomes in these patients.

Association of androgenetic alopecia with a more severe form of COVID-19 infection.

BACKGROUND: Individual susceptibility to develop acute respiratory distress syndrome is related to age and most frequent comorbidities. So far, it is known that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) primarily infects the type II pneumocytes in humans, with the help of transmembrane serine protease type 2 (TMPRSS2). Up to now, the only known transcriptional promoters of genes coding TMPRSS2 are androgenic. Theoretically, the elevated level of androgens or androgen receptors would lead to a higher expression of TMPRSS2 and a higher level of viremia as a consequence. AIM: The aim of our research was to indirectly investigate if the severity of SARS-CoV-2 infection is dependent on the expression of androgen receptors. METHODS: This observational study analysed male patients hospitalized for SARS-CoV-2 infection with respect to the length of hospitalisation, the outcome of the disease, the type of necessary oxygen support and the presence of comorbidities and hairiness. In hairiness estimation, we used an adapted version of the Hamilton-Norwood scale and the presence of the Gabrin sign. RESULTS: In total, 208 patients were enrolled in the study. There were statistically significant differences comparing the average age of patients with the different types of alopecia when groups were divided according to the presence of the Gabrin sign (t = 4.958, p > 0.01). The outcomes and the type of needed minimal oxygen support, compared with the type of alopecia in the case of Gabrin + / - classification showed a statistically significant difference in the outcome of the disease (p = 0.027). There were no statistically significant differences in the distribution of comorbidities among alopecia groups, but hypertension was related to poor COVID-19 prognosis. CONCLUSION: Our findings suggest that the Gabrin sign and hypertension are related to a poor COVID-19 prognosis.

The Wnt/ß-catenin Signalling Pathway Inhibitor Sclerostin is a Biomarker for Early Atherosclerosis in Obesity.

BACKGROUND: Sclerostin is an inhibitor of the wingless-type mouse mammary tumor virus integration site family/ß-catenin signalling pathway (WßcSP), which plays an important role in bone metabolism and in vascular biology. It could act protective regarding atherosclerosis development through its effect on WßcSP in vascular cells. Nevertheless, results of studies analyzing association between circulating sclerostin level (CSL) and atherosclerotic diseases (AD) are showing conflicting results. The aim of this study is to test the value of CSL as a biomarker of subclinical carotid atherosclerosis (SCA) in obese persons. METHODS: The cross-sectional study included 50 obese persons without previous history of diabetes and AD. Participants underwent adequate anthropometrical, ultrasound and laboratory examinations, including 2h 75 g oral glucose tolerance test (OGTT). RESULTS: Only the presence of SCA significantly indirectly correlated with CSL (p<0.05). Based on the median value of CSL, we formed two groups: low CSL (CSL<7.9 pmol/l) and high CSL (CSL>7.9 pmol/l). There were no statistically significant differences in general (gender, age and current smoking) and anthropometrical characteristics (body mass index, waist circumference, systolic and diastolic blood pressure), inflammatory (total white blood cell count, erythrocyte sedimentation rate, fibrinogen, C-reactive protein and uric acid), glucose metabolism (fasting and 2h OGTT blood glucose, glycated hemoglobin and presence of dysglycemia) and lipid metabolism (low density lipoprotein cholesterol, high density lipoprotein cholesterol, triglycerides, apolipoprotein A-I, apolipoprotein B and lipoprotein (a)) parameters between low and high CSL groups. Low CSL group had significantly higher incidence of SCA (p<0.05). CONCLUSION: CSL could serve as a useful biomarker of early atherosclerosis in obese persons without previous history of cardiometabolic disorders but the final conclusion requires further testing.

Multiple Causes of Hyponatremia: A Case Report.

OBJECTIVE: To present a case with 4 different potential causes of hyponatremia. CLINICAL PRESENTATION AND INTERVENTION: The patient presented with the following symptoms: nausea, vomiting, diarrhea, and dark urine after drinking large amounts of fluids that included alcohol and caffeine. Laboratory, microbiological, and morphological examinations revealed the existence of severe hyponatremia and acute poststreptococcal glomerulonephritis. The patient developed acute symptomatic seizures and coma. Gradual normalization of the sodium level led to a recovery of consciousness. CONCLUSION: Treatment with hypertonic sodium, fluid restriction, and antibiotics led to a complete recovery. In the case of multiple causes of hyponatremia, it is necessary to treat all causes.

Surrogates of Insulin Sensitivity and Indices of Cardiometabolic Profile in Obesity.

BACKGROUND AND OBJECTIVES: Obesity is often associated with insulin resistance (IR). We considered different IR indexes: the Homeostasis Model Assessment-Insulin Resistance (HOMA-IR) index, the two specimen (0 and 120 min) oral glucose tolerance test Matsuda Index (MI) and the Homeostasis Model Assessment-Adiponectin (HOMA-AD) index. These IR indexes were compared with indicators of the cardiometabolic profile. METHOD: This cross-sectional study enrolled 60 obese individuals without previous history of diabetes. Anthropometrical, ultrasound and laboratory examinations were conducted. RESULTS: All 3 indexes significantly correlated with indicators of central obesity, systolic and diastolic blood pressure, inflammation parameters, liver enzymes, HbA1c and some lipid parameters. The majority of correlation coefficients were the highest for HOMA-AD, but only the difference in correlation with waist circumference comparing with MI was statistically significant. HOMA-IR directly, and MI indirectly, significantly correlated with age, while HOMA-AD significantly directly correlated with the mean carotid artery intima media thickness (CAIMT). MI showed the best performances in predicting non-alcoholic fatty liver disease and pathologically increased CAIMT; HOMA-AD was the best in predicting metabolic syndrome, while HOMA-IR demonstrated the poorest performances in the prediction of all 3 conditions. There were no statistically significant differences in predicting performances of the analysed indexes. CONCLUSION: The HOMA-AD and MI are not superior compared with the HOMA-IR, in the identification of obese individuals with a proatherogenic cardiometabolic profile.

Possible influence of the environmental pollutant bisphenol A on the cardiometabolic risk factors.

Bisphenol A (BPA) is a ubiquitous environmental pollutant which is often associated with various health issues. In this study 103 healthy female volunteers in reproductive age from Serbian north province Vojvodina were enrolled and examined for the BPA exposure in the urine samples after 12 h of fasting. BPA was found in 35.92 % (37/103) of subjects. Statistically significant increment in waist circumference (p = 0.045) and waist-to-height ratio (p = 0.037) was observed among the BPA positive women in comparison with the women who had the same energetic balance and had not been exposed to BPA. Linear correlation was obtained between the BPA concentration in urine samples and body mass index (r2 = 0.35, p = 0.003) waist circumference (r2 = 0.21, p = 0.02) and waist-to-height ratio (r2 = 0.25, p = 0.01) among the obese. High energetic intake and reduced physical activity additionally pronounced BPA positive association with obesity. No statistically significant difference was observed in triglycerides, HDL and LDL cholesterol levels between the BPA exposed and BPA non-exposed female volunteers.

Do diethyl phthalate (DEP) and di-2-ethylhexyl phthalate (DEHP) influence the metabolic syndrome parameters? Pilot study.

The study objective was to determine if the healthy participants were exposed to diethyl phthalate (DEP) and di (2-ethylhexyl) phthalate (DEHP) and if this exposure could be linked to the development of metabolic syndrome. The study included 103 healthy volunteers of similar age with normal BMI values, waist circumference, total cholesterol, HDL, LDL, and triglycerides. DEP and DEHP were measured in the morning urine samples to detect monoethyl phthalate (MEP) and mono-2-ethylhexyl phthalate (MEHP). Two phthalate groups and a control group were formed. Both MEP group and control group had similar results. The correlations between MEP and the measured parameters were insignificant. The correlation between the MEHP group and the age was significantly negative, but between the MHEP group and the waist circumference the correlation was significantly positive. Lipids and lipoproteins were within the reference values and equal in both groups. The significant negative correlation was observed only between MEHP and HDL. Our population is exposed to DEP and DEHP. There was only a significant correlation between DEHP and the observed metabolic syndrome components. Its negative impact was higher as the participants were younger.

Osteoporosis reversibility in a patient with celiac disease and primary autoimmune hypothyroidism on gluten free diet--a case report.

INTRODUCTION: Secondary osteoporosis occurs in many diseases. Celiac disease-induced osteoporosis is the consequence of secondary hyperparathyroidism. Biochemical bone markers show predominance of bone resorption, thus making the bisphosphonates the first line therapy option. Intestinal mucosal changes are reversible on gluten-free diet. Osteoporosis reversibility is also possible, provided postmenopausal osteoporosis risk factors independent from celiac disease are not present. CASE REPORT: We presented a postmenopausal woman with at least a 10-year history of celiac disease prior to diagnosis, which had overt secondary hyperparathyroidism with insufficient status of vitamin D and a significant bone mass reduction. At the time of diagnosis of celiac disease the patient was receiving 250 µg of levothyroxine daily without achieving optimal substitution. Three years after the initiation of gluten-free diet the patient was without any signs and symptoms of the disease. All laboratory findings were within normal range. It was decided to treat the underlying disease and to supplement calcium and vitamin D without the initiation of bisphosponate therapy. CONCLUSION: Osteoporosis regression justified this therapeutic approach. The presence of primary autoimmune hypothyroidism makes this case specific, since the inability for optimal substitution therapy with a high daily dose of levothyroxine provoked the suspicion of celiac disease.

Risk factors for accelerated atherosclerosis in young women with hyperprolactinemia.

Prolactin is a metabolic hormone. The hypothesis is that hyperprolactinemia can cause metabolic and inflammatory changes which are associated with accelerated atherosclerotic process, but the treatment of hyperprolactinemia with dopamine agonists, leads to reversibility of these processes. The first aim of this study was to determine whether hyperprolactinemia in premenopausal women is accompanied with the increase in body mass index (BMI), changes in body composition, lipid disturbances, the presence of inflammation and changes in systolic and diastolic blood pressure as risk factors for the development of early atherosclerosis. The second aim was to know whether the therapy of hyperprolactinemia and prolactin normalization lead to improvement of the observed parameters. Twenty female patients with prolactinomas, before and during treatment with dopamine agonists and 16 healthy controls were evaluated. Prolactin, BMI, total body fat, free fat mass, total body water, total cholesterol, triglycerides, high density lipoprotein (HDL), low density lipoprotein (LDL) and fibrinogen as well as systolic and diastolic blood pressure were measured at baseline and during the therapy. Hyperprolactinemic patients had pathologic and significantly higher levels of prolactin (PRL) than the controls (p=0.000). The BMI, body fat, total body water (TBW), total cholesterol, triglycerides, LDL were in normal range and higher in the patients than in the controls. HDL was lower in hyperprolactinemic females than controls. The difference was significant only for body fat (fat % p=0.006; fat kg p=0.009). Fibrinogen was slightly increased in patients compared with the controls. Hyperprolactinemic patients had normal, but increased levels of systolic and diastolic blood pressure compared with the controls. The difference with border significance was found in diastolic blood pressure (p=0.065). The correlation of PRL with all the observed parameters was positive apart from HDL, but relatively significant only with diastolic blood pressure (r=0.31). The therapy with dopamine agonists caused the decrease of all the observed parameters, but significant decreases was achieved only in BMI (p=0.028), total cholesterol levels (p<0.001) and LDL (p<0.002). Changes in BMI, body composition, serum lipids and lipoproteins, fibrinogen level and blood pressure confirm our hypothesis about the possible role of hyperprolactinemia in developing adverse metabolic disturbances which are reversible after treatment.

Effects of phthalic acid esters on fetal health.

INTRODUCTION: Phthalates are synthetic industrial compounds capable of disrupting endocrine system. Effects of phthalates depend on dosage, duration of action and stage of development of the individual, thus making the fetus, newborn, and children at puberty the most vulnerable groups. METABOLISM OF PHTHALATES: Metabolism of these compounds consists of at least two steps: hydrolysis and conjugation. They are mainly excreted in urine, with a low percent being excreted through feces. EXPOSURE TO PHTHALATES: Exposure to the effects of phthalates begins at the intrauterine stage since the phthalates pass through the placental barrier. Phthalates may be found in plastic products, toys, medical equipment, industrial materials, food, and clothes. DETERMINATION OF PHTHALATE LEVELS IN HUMANS: Urine is the best sample for evaluating phthalate levels in humans because of rapid phthalate metabolism and high concentrations of metabolites in the urine. FETAL TESTICULAR DYSGENESIS SYNDROME: Fetal testicular dysgenesis syndrome involves disorders of male genital tract such as shortened anogenital distance, hypospadia, cryptorchidism, malformations of seminal vesicles, prostate, epididymis and it results from the harmful effects of phthalates. OTHER EFFECTS OF PHTHALATES ON HEALTH: Negative effects of phthalates on female health are mostly reflected in anovulation, premature puberty, changes in duration of pregnancy. There is a possible effect on neurocognitive development, occurrence of allergies, asthma, testicular carcinoma, hepatic and renal damages, insulin resistance and obesity, thyroid dysfunction. CONCLUSION: Further studies are needed to establish the safe phthalate concentration in certain products and to determine more negative consequences of exposure to phthalate.

[Iodine and thyroid gland with or without nuclear catastrophe].

INTRODUCTION: Iodine, as a trace element, is a necessary and limiting substrate for thyroid gland hormone synthesis. It is an essential element that enables the thyroid gland to produce thyroid hormones thyroxine (T4) and triiodothyronine (T3). Synthesis of Thyroid Hormones and Iodine Metabolism. Three iodine molecules are added to make triiodothyronine, and four for thyroxine - the two key hormones produced by the thyroid gland. Iodine deficiency The proper daily amount of iodine is required for optimal thyroid function. Iodine deficiency can cause hypothyroidism, developmental brain disorders and goiter. Iodine deficiency is the single most common cause of preventable mental retardation and brain damage in the world. It also decreases child survival, causes goiters, and impairs growth and development. Iodine deficiency disorders in pregnant women cause miscarriages, stillbirths, and other complications. Children with iodine deficiency disorders can grow up stunted, apathetic, mentally retarded, and incapable of normal movements, speech or hearing. Excessive Iodine Intake. Excessive iodine intake, which can trigger a utoimmune thyroid disease and dysfunction. is on the other side. Iodine use in Case of Nuclear Catastrophe. In addition to other severe consuquences of radioactivity, high amount of radioactive iodine causes significant increase in incidence of thyroid gland carcinoma after some of the nuclear catastrophes (Hiroshima, Nagasaki, Chernobyl, Fukushima). The incidence of thyroid carcinoma was increased mostly in children. This paper was aimed at clarifying some of the possibilities of prevention according to the recommendations given by the World Health Organization.

Influence of glucoregulation quality on C-reactive protein, interleukin-6 and tumor necrosis factor-alpha level in patients with diabetes type 1.

BACKGROUND/AIM: Results of studies which have proved an increased inflammatory activity in diabetes type 1, have been published over recent years. One of possible mechanisms that are used to explain chronic inflammation in diabetes is the state of hyperglycemia leading to the enhanced synthesis of glycosylation end products (AGEs) which activate macrophages, increase the oxidative stress and affect the synthesis of interleukins (IL-1, IL-6), tumor necrosis factor-alpha (TNF-alpha) and C-reactive protein (CRP). The aim of the study was to determine the inflammatory markers (CRP, IL-6, TNF-alpha) in patients with diabetes type 1 and to establish their correlation with glucoregulation parameters and other cardiovascular risk factors as well as to compare them with the healthy controls. METHODS: The study included 76 patients with diabetes type 1 and 30 healthy controls. We determined values of inflammatory markers (CRP, IL-6, TNF-alpha) and glucoregulation parameters (fasting glucose HbA(1c)). RESULTS: The values of CRP (p = 0.014), IL-6 (p = 0.020) and TNF-alpha (p = 0.037) were statistically significantly higher in the diabetic patients than in the healthy controls. There was a positive correlation between CRP with postprandial glycemia (p = 0.004); the multivariate regression analysis revealed a statistically significant correlation between CRP and age (p = 0.001), smoking (p = 0.055), fasting glucose (p = 0.021) and triglycerides (p = 0.048) as well as between IL-6 and LDL-cholesterol (p = 0.009). No statistically significant correlations were found between glycosilated hemoglobin (HbA(1c)) and the inflammatory markers (CRP, IL-6 and TNF-alpha). CONCLUSION: The patients with type 1 diabetes were found to have a low level of inflammatory activity manifested by the increased values of CRP, IL-6 and TNF-alpha.

[Autoimmune thyroid disease and other non-endocrine autoimmune diseases].

INTRODUCTION: Autoimmune diseases are chronic conditions initiated by the loss of immunological tolerance to self-antigens. They constitute heterogeneous group of disorders, in which multiple alterations in the immune system result in a spectrum of syndromes that either target specific organs or affect the body systematically. Recent epidemiological studies have shown a possible shift of one autoimmune disease to another or the fact that more than one autoimmune disease may coexist in a single patient or in the same family. Numerous autoimmune diseases have been shown to coexist frequently with thyroid autoimmune diseases. AUTOIMMNUNE THYROID DISEASE AND OTHER ORGAN SPECIFIC NON-ENDOCRINE AUTOIMMUNE DISEASES: This part of the study reviews the prevalence of autoimmune thyroid disease coexisting with: pernicious anaemia, vitiligo, celiac disease, autoimmune liver disease, miastenia gravis, alopecia areata and sclerosis multiplex, and several recommendations for screening have been given. AUTOIMMUNE THYROID DISEASE AND OTHER ORGAN NON-SPECIFIC NON-ENDOCRINE AUTOIMMUNE DISEASES: Special attention is given to the correlation between autoimmune thyroid disease and rheumatoid arthritis, systemic lupus erythematosus, syndrome Sjögren, systemic sclerosis and mixed connective tissue disease. CONCLUSIONS: Screening for autoimmune thyroid diseases should be recommended in everyday clinical practice, in patients with primary organ-specific or organ non-specific autoimmune disease. Otherwise, in patients with primary thyroid autoimmune disease, there is no good reason of seeking for all other autoimmune diseases, although these patients have a greater risk of developing other autoimmune disease. Economic aspects of medicine require further analyzing of these data, from cost/benefit point of view to justified either mandatory screening or medical practitioner judgment.

[Hormone replacement therapy and cardiovascular risk in postmenopausal women].

Five years after the menopause, we can see the increase in cardiovascular risk due to prolonged deficiency of ovarian hormones. These risks are the same or even more severe than those in men within the same age group. The basic influence of normalizes those disturbances. In 2002. published data from a WHI study show an increase in cardiovascular risk during the first year of hormone replacement therapy with no protective effect. The most recent published data from WHI study show positive effects of hormone replacement therapy, within postmenopausal women younger than 65 years. Those women had significantly reduced calcifications on coronary vessels The American Association of Clinical Endocrinologists and the estrogens can be genomic and non genomic. Estrogens influence endothelia and smooth muscle wall of arterial blood vessels, metabolism of lipoproteins and induce the metabolic syndrome. Hormone replacement therapy partially or completely International Menopause Society proclaim that the hormone replacement therapy can prevent cardiovascular diseases and slow down the progress of atherosclerosis. The aim of ongoing KEEPS is to investigate the preventive effect of the hormone replacement therapy on blood vessels, in early postmenopausal period (women younger than 60 year). This study should be valid enough to define new clinical knowledge about the hormone replacement therapy and cardiovascular risk.