Galectin-1 in Pancreatic Ductal Adenocarcinoma: Bridging Tumor Biology, Immune Evasion, and Therapeutic Opportunities.

Pancreatic Ductal Adenocarcinoma (PDAC) remains one of the most challenging malignancies to treat, with a complex interplay of molecular pathways contributing to its aggressive nature. Galectin-1 (Gal-1), a member of the galectin family, has emerged as a pivotal player in the PDAC microenvironment, influencing various aspects from tumor growth and angiogenesis to immune modulation. This review provides a comprehensive overview of the multifaceted role of Galectin-1 in PDAC. We delve into its contributions to tumor stroma remodeling, angiogenesis, metabolic reprogramming, and potential implications for therapeutic interventions. The challenges associated with targeting Gal-1 are discussed, given its pleiotropic functions and complexities in different cellular conditions. Additionally, the promising prospects of Gal-1 inhibition, including the utilization of nanotechnology and theranostics, are highlighted. By integrating recent findings and shedding light on the intricacies of Gal-1's involvement in PDAC, this review aims to provide insights that could guide future research and therapeutic strategies.

Hypertension in Polycystic Ovary Syndrome: Novel Insights.

Polycystic ovary syndrome (PCOS) is a common endocrine disease in women during reproductive age. It was shown that PCOS women are with high risk for dyslipidemia, glucose intolerance, type 2 diabetes and metabolic syndrome. These factors are considered to represent traditional risk factors for the occurrence of cardiovascular disease. Observed increased risk for hypertension in PCOS women seems to be associated with insulin resistance and hyperinsulinemia. Both conditions interfere with the endothelium-dependent vasodilatation mechanisms causing vascular muscle wall hypertrophy. Obesity and insulin resistance are considered key factors for the alteration of blood pressure in PCOS women. Higher cardiovascular risk is implicated in PCOS with aging and its consequent association with both systolic and diastolic blood pressure. The elements of renin-angiotensin-aldosterone system (RAAS) have an impact on endothelial dysfunction as a marker of cardiovascular damage that could be modified is women with PCOS. Androgens and components of RAAS are involved in the process of atherogenesis in PCOS women. Therefore, it is hypothesized that spironolactone treatment could ameliorate endothelial dysfunction in PCOS women. Recently it was shown that telmisartan, angiotensin II receptor antagonist poses insulinsensitizing capacity to activate PPAR gamma and mediate favorable metabolic and reproductive effects in hypertensive PCOS women.

Nonalcoholic Fatty Liver Disease in Patients with Polycystic Ovary Syndrome.

Polycystic ovary syndrome (PCOS) is the most common endocrine disease in women during the reproductive period. True PCOS phenotype is prone to develop metabolic consequences during life. Obese PCOS women with insulin resistance are carrying a risk for developing type 2 diabetes, and influencing liver function by generating liver steatosis and nonalcoholic fatty liver disease (NAFLD). Moreover, serum testosterone of over 3 nmol/L is associated with at least two-fold higher risk for the development of NAFLD in PCOS women. Numerous genes involved in the pathogenesis of hyperandrogenism, insulin resistance and inflammation are associated with the development of NAFLD in PCOS women. Liver biopsy is not considered as the first line procedure for the diagnosis of liver damage in a prevalent condition as PCOS. Therefore, simple and reliable surrogate markers as serum aminotransferases levels or surrogate indexes (i.e. fatty liver index and NAFLD-fatty liver score) could be used for the assessment of fatty liver in PCOS women. First line therapeutic approach for NAFLD in PCOS includes a change in lifestyle that implies dietary regiment and physical activity but without well-defined protocols. Second line therapy considers addition of drugs on the established lifestyle change. Metformin remains the drug of choice for reduction of insulin resistance and liver enzymes level. Liraglutide, glucagon-like peptide-1 receptor agonists, showed favorable effects on the reduction of liver fat content and visceral adipose tissue in overweight women with PCOS. Current review analyzes the impact of metabolic risk factors, diagnostic approach and management options on NAFLD in women with PCOS.

Effects of cardiovascular drugs on TSH serum levels in patients on replacement therapy after thyroidectomy.

OBJECTIVE: Hypothyroidism is one of most common endocrine disorders resulting from deficiency of thyroid hormones. The aim of our study was to investigate whether cardiovascular drugs as well as gender, age, body-mass index, and habits, like smoking or drinking coffee affect thyroid-stimulating hormone (TSH) level in hypothyroid patients with thyroxine replacement therapy who suffer from cardiovascular disease. MATERIALS: The study was conducted on 150 hypothyroid patients who underwent total thyroidectomy for benign reasons; they were divided into five treatment groups: levothyroxine only group and, according to the drugs they had in therapy alongside levothyroxine, the angiotensinconverting enzyme inhibitors group, the selective ß-blockers group, the calcium antagonists group, as well as the nitrates group. A retrospective cohort study was conducted in the Clinical Center Kragujevac, Serbia, during the period of January 2012 to October 2014. All patients' data were collected both from participants' health records and questionnaires that patients completed, including data about habits, like smoking or drinking coffee. RESULTS: TSH values were significantly higher in the group of patients with selective ß-blockers in therapy alongside levothyroxine, compared to all the other study groups. The values of TSH level did not significantly differ among the other therapy groups. On the other hand, cigarette smoking was a risk factor that decreased TSH levels in patients on thyroid replacement therapy. CONCLUSIONS: Our study shows that selective ß-1 blockers can increase, while cigarette smoking can decrease TSH serum levels in hypothyroid patients on thyroid-replacement therapy.

Parameters of Calcium Metabolism Fluctuated during Initiation or Changing of Antipsychotic Drugs.

OBJECTIVE: Serum parameters of calcium homeostasis were measured based on previously published evidence linking osteoporotic fractures and/or bone/mineral loss with antipsychotics. METHODS: Prospective, four-week, time-series trial was conducted and study population consisted of patients of both genders, aged 35-85 years, admitted within the routine practice, with acute psychotic symptoms, to whom an antipsychotic drug was either introduced or substituted. Serial measurements of serum calcium, phosphorous, magnesium, 25(OH)D, parathyroid hormone, calcitonin, osteocalcin and C-telopeptide were made from patient venous blood samples. RESULTS: Calcium serum concentrations significantly decreased from baseline to the fourth week (2.42±0.12 vs. 2.33±0.16 mmol/L, p=0.022, n=25). The mean of all calcemia changes from the baseline was -2.6±5.7% (-24.1 to 7.7) with more decreases than increases (78 vs. 49, p=0.010) and more patents having negative sum of calcemia changes from baseline (n=28) than positive ones (n=10) (p=0.004). There were simultaneous falls of calcium and magnesium from baseline (63/15 vs. 23/26, p<0.001; OR=4.75, 95% CI 2.14-10.51), phosphorous (45/33 vs. 9/40, p<0.001; 6.06, 2.59-14.20) and 25(OH)D concentrations (57/21 vs. 13/35, p<0.001; 7.31, 3.25-16.42), respectively. Calcemia positively correlated with magnesemia, phosphatemia and 25(OH)D values. Parathyroid hormone and C-telopeptide showed only subtle oscillations of their absolute concentrations or changes from baseline; calcitonin and osteocalcin did not change. Adjustment of final calcemia trend (depletion/accumulation) for relevant risk factors, generally, did not change the results. CONCLUSION: In patients with psychotic disorders and several risks for bone metabolism disturbances antipsychotic treatment was associated with the decrease of calcemia and changes in levels of the associated ions.

Giant liver hemangioma in patient with ileal gastrointestinal stromal tumor.

INTRODUCTION: Gastrointestinal stromal tumors are the most common mesenchymal neoplasms of the gastrointestinal tract. These tumors represent more than 80% of all mesenchymal tumors found in the gastrointestinal tract, though they account for only approximately 3% of all gastrointestinal malignancies. Literature offers case reports, which describe symptomatic gastrointestinal stromal tumors and they generally represent patients with larger tumors. CASE REPORT: We present the case of a small gastrointestinal stromal tumor in a 40-year-old man, with associated giant liver hemangioma and fever, and with history of abdominal discomfort and fever. Clinical examination revealed hepatosplenomegaly, palpable mass in the right lower abdomen, and signs of neurofibromatosis type 1 (Morbus von Recklinghausen). Computed tomography revealed a giant tumor in the right lobe of the liver. Magnetic resonance showed abscess in the hemangioma of the liver. An intestinal tumor was incidentally found and excised during surgical laparotomy. An intestinal gastrointestinal stromal tumor was revealed by histopathology and confirmed by immunohistochemistry. Although a multidisciplinary team proposed surgical removal of the liver tumor mass, the surgeons decided to follow up the patient because of a high risk of new intervention. CONCLUSION: According to the available data, this is a very rare case of small intestinal gastrointestinal stromal tumor, with symptoms of fever and giant abscess in the liver hemangioma.

NT-proBNP for prognostic and diagnostic evaluation in patients with acute coronary syndromes.

BACKGROUND AND AIM: N terminal-proB-type natriuretic peptide (NT-proBNP) is synthesised and secreted from the ventricular myocardium. This marker is known to be elevated in patients with acute coronary syndromes (ACS). We evaluated NT-proBNP asa significant diagnostic marker and an important independent predictor of short-term mortality (one month) in patients with ACS. METHODS: NT-proBNP and cardiac troponin I (cTI) were assessed in 134 consecutive patients (median age 66 years, 73% male)hospitalised for ACS in a cardiological university department. The patients were classified into ST-elevation ACS (STE-ACS, n = 74) and non-ST-elevation ACS (NSTE-ACS, n = 60) groups based on the ECG findings on admission. Patients with Killip class ≥ II were excluded. RESULTS: The serum level of NT-proBNP on admission was significantly higher (p < 0.0005), while there was no difference in cTI serum level in the NSTE-ACS patients compared to STE-ACS patients. There was a significant positive correlation between NT-proBNP and cTI in the NSTE-ACS (r = 0.338, p = 0.008) and STE-ACS (r = 0.441, p < 0.0005) patients. There was a significant difference in NT-proBNP (p < 0.0005) and cTI (p < 0.0005) serum level between ACS patients who died within 30 days or who survived after one month. The increased NT-proBNP level is the strongest predictor of mortality in ACS patients, also NT-proBNP cut-point level of 1,490 pg/mL is a significant independent predictor of mortality. CONCLUSIONS: We demonstrated the differences and the correlation in the secretion of NT-proBNP and cTI in patients with STE-ACS vs. NSTE-ACS. Our results provide evidence that NT-proBNP is a significant diagnostic marker and an important independent predictor of short-term mortality in patients with ACS.

[Changes in parameters of glycoregulation in gestational diabetes mellitus patients with different approach to insulin therapy introduction].

INTRODUCTION: Gestational diabetes mellitus (GDM) is defined as any degree of glucose intolerance with onset or first recognition during pregnancy. The diagnosis of GDM is made by performing the oral glucose tolerance test (OGTT) in women with risk factors, usually during 24th to 28th week of gestation. The most common used insulin therapy regime is a conventional intensive insulin therapy with four daily doses. OBJECTIVE: The aim of our study was to determine the changes in parameters of glycoregulation in GDM patients with different approach to the introduction of insulin therapy. METHODS: Study group consisted of 50 pregnant women divided into two groups depending on the parameters of glycoregulation (glycemic profile and HbA1). Group 1 consisted of pregnant women initially treated with diet only and then, according to glycemic profile and HbA1 profile, in the next few weeks with insulin therapy. Group 2 were pregnant women who were treated with insulin therapy immediately after GDM diagnosis. RESULTS: There was a statistically significant difference in mean glycemia values in the 60th and 120th minute between the two groups (p = 0.001). There was a difference in mean value of fasting blood and postprandial glucose between the two groups; it was higher in Group 2. There was a statistically significant difference between the two groups in HbA1c value at the beginning (5.1 +/- 0.4% vs. 5.42 +/- 0.43%, p = 0.005) and at the end of therapy (4.87 +/- 0.29% vs. 5.1 +/- 0.39 %, p = 0.018). CONCLUSION: Satisfactory glycoregulation was achieved in both studied groups.

Influence of admission plasma glucose level on short- and long-term prognosis in patients with ST-segment elevation myocardial infarction.

BACKGROUND/AIM: Hyperglicemia is common in patients with ST-elevation myocardial infarction (STEMI) and is associated with high risk of mortality and morbidity. Relationship between admission plasma glucose (APG) levels and mortality in diabetic and nondiabetic patients with STEMI needs further investigation. The aim of this study was to analyse the short- and long-term prognostic significance of APG levels in patients with STEMI with and without diabetes. METHODS: This study included 115 patients with STEMI, 86 (74.8%) nondiabetic and 29 (25.2%) dibaetic patients, in which we performed a prospective analysis of the relationship between APG levels and short- and long-term mortality. RESULTS: Comparison of APG levels between nondiabetic (8.32 +/- 2.4 mmol/L) and diabetic (10.09 +/- 2.5 mmol/L) patients showed statistically significantly higher average APG levels in diabetic patients (p = 0.001). In all patients observed who died either after one month or one year after STEMI, average APG values were significantly higher in comparison with those in survived patients. There was no statistical significance in average APG levels in the diabetic patients with STEMI who died after one month and those who survived (10.09 +/- 2.68 vs 10.0 +/- 2.51 mmol/L, respectively; p = 0.657), as well as those who died after one year and those who survived (10.1 +/- 1.92 vs 10.09 +/- 2.8 mmol/L, respectively; p = 0.996). There was, however, statistical significance in average APG levels in the nondiabetic patients with STEMI who died after one month and those who survived (9.97 +/- 2.97 vs 7.91 +/- 2.08 mmol/L, respectively; p = 0.001), as well as those who died after one year and those who survived (9.17 +/- 2.49 vs 7.84 +/- 2.24 mmol/L, respectively; p = 0.013). CONCLUSION: Acute hyperglicemia in the settings of STEMI worsenes the prognosis in patients with and without diabetes. Our study showed that nondiabetic patients with high APG levels are at higher risk of mortality than patients with a known history of diabetes.