Crosstalk between Serum and Skin Sphingolipids in Psoriasis.

Psoriasis is a chronic, complex, immunological disorder, which may lead to many different systemic complications. Sphingolipids, including ceramide, are bioactive lipids, which take part in the regulation of immune reactions, cell growth, and apoptosis. Twenty psoriatic patients and twenty-eight control subjects were included in the study. Skin (both lesional and non-lesional) and serum samples were collected from both the control group and the psoriatic patients. The levels of sphingosine (SFO), sphingosine-1-phosphate (S1P), sphingomyelin, sphinganine (SFA), sphinganine-1-phosphate (SFA1P), and ceramide (CER) were assessed in both tissue (t) and serum (s) samples using high-performance liquid chromatography (HPLC). We identified elevated serum levels of SFO, S1P, SFA, and SFA1P in psoriatic patients when compared to healthy individuals. As far as the lesional skin and serum of psoriatic patients are concerned, we demonstrated positive associations between CER_t and CER_s, SFA_t and CER_s, and SFO_t and CER_s. Additionally, we found negative correlations in the non-lesional skin and serum of psoriatic patients, including SFO_t vs. SFO_s, CER_t vs. SFA_s, CER_t vs. SFO_s, and SFO_t vs. SFA_s. Finally, we observed a positive correlation between S1P and SFA1P in both the serum samples of psoriatic patients and the serum samples of the control group. In this study, we did not observe any correlations between psoriasis area and severity index (PASI) scores and sphingolipid levels. In conclusion, our findings indicate an interplay between skin and serum lipids in psoriatic patients, which is not observed in healthy individuals.

The Interplay between Bioactive Sphingolipids in the Psoriatic Skin and the Severity of the Disease.

Psoriasis is a complex chronic immunologically mediated disease that may involve skin, nails, and joints. It is characterized by hyperproliferation, deregulated differentiation, and impaired apoptosis of keratinocytes. Sphingolipids, namely ceramide, sphingosine-1-phosphate, sphingosine, sphingomyelin, and sphinganine-1-phosphate, are signal molecules that may regulate cell growth, immune reactions, and apoptosis. Fifteen patients with psoriasis and seventeen healthy persons were enrolled in the study. Skin samples were taken from psoriatic lesions and non-lesional areas. Tissue concentration of ceramides, sphingosine-1-phosphate, sphingosine, sphingomyelin, and sphinganine-1-phosphate was measured by liquid chromatography. We assessed that all levels of ceramides, sphingosine-1-phosphate, sphingosine, sphingomyelin, and sphinganine-1-phosphate were higher in lesioned psoriatic skin than in non-affected skin. The profile of bioactive lipids in the lesional skin of patients with psoriasis differed significantly from non-involved psoriatic skin and skin in healthy subjects.

Antioxidant and antiradical activities depend on adrenal tumor type.

The aim of the study was to assess the total antioxidant/oxidant status in the plasma and urine of patients with adrenal tumors. The study group consisted of 60 patients (31 women and 29 men) with adrenal masses, classified into three subgroups: non-functional incidentaloma, pheochromocytoma and Cushing's/Conn's adenoma. The number of patients was set a priori based on our previous experiment (α = 0.05, test power = 0.9). Antioxidant activity (Total Antioxidant Capacity (TAC), Total Oxidant Status (TOS), Oxidative Stress Index (OSI)) and antiradical activity (Radical-Scavenging Activity Assay (DPPH), Ferric-Reducing Antioxidant Power (FRAP)) were measured using colorimetric methods. FRAP level was decreased in plasma and urine incidentaloma (p<0.0001), pheochromocytoma (p<0.0001) and Cushing's/Conn's adenoma (p<0.0001), while DPPH antiradical activity only in plasma of patients with adrenal masses (p<0.0001). Plasma TAC was increased in incidentaloma patients (p=0.0192), whereas in pheochromocytoma group (p=0.0343) was decreased. Plasma and urine TOS (p<0.0001) and OSI (p<0.01) were significantly higher in patients with adrenal tumors. In pheochromocytoma patients, plasma and urine TAC (p=0.001; p=0.002), as well as plasma plasma DPPH (p=0.007) and urine FRAP (p=0.017) correlated positively with normethanephrine. We are the first who showed reduced radical scavenging capacity in the plasma/urine of patients with adrenal masses. Nevertheless, plasma TAC was significantly higher in the incidentaloma group compared to controls. Therefore, plasma and urinary antioxidant and antiradical activities depend on the presence of the tumor. Lower levels of TAC, DPPH and FRAP clearly indicate a reduced ability to scavenge free radicals and thus a lack of effective protection against oxidative stress in patients with adrenal tumors. Both plasma and urine redox biomarkers can be used to assess systemic antioxidant status in adrenal tumor patients.

Cross-Talk Between Nitrosative Stress, Inflammation and Hypoxia-Inducible Factor in Patients with Adrenal Masses.

BACKGROUND: Adrenal masses are the most common of all human tumors. The role of nitrosative stress and inflammation in cancer development has already been demonstrated. However, it is not known whether they are involved in the pathogenesis of adrenal tumors. The aim of the study was to investigate a cross-talk between nitrosative stress, inflammation and hypoxia-inducible factor (HIF-1α) in 75 patients with different types of adrenal masses (non-functional incidentaloma, pheochromocytoma and Cushing's/Conn's adenoma). METHODS: The plasma concentrations of total nitric oxide (NO), S-nitrosothiols, peroxynitrite nitrotyrosine and the activity of serum myeloperoxidase (MPO) were measured spectrophotometrically, whereas concentrations of interleukin 1 beta (IL-1ß), tumor necrosis factor α (TNF-α) and hypoxia-inducible factor 1 alpha (HIF-1α) were measured using commercial ELISA kits. The control group consisted of 50 healthy people matched by age and sex to the study group. The number of subjects was determined a priori based on our previous experiment (power of the test = 0.9; α = 0.05). RESULTS: We found significantly higher nitrosative stress (↑nitric oxide, ↑peroxynitrite, ↑S-nitrosothiols and ↑nitrotyrosine) in the plasma of patients with adrenal tumors, which was accompanied by increased inflammatory (↑myeloperoxidase, ↑interleukin 1 beta and ↑tumor necrosis factor α) and hypoxia (HIF-1α) biomarkers. Peroxynitrite and nitrotyrosine were positively correlated with aldosterone level. Nitrosative stress was also associated with inflammation and HIF-1α. Interestingly, plasma nitrotyrosine and serum MPO differentiated patients with adrenal tumor from healthy individuals with high sensitivity and specificity. Moreover, using multivariate regression analysis, we showed that ONOO- and IL-1ß depended on cortisol level, while ONOO-, nitrotyrosine and HIF-1α were associated with aldosterone. Unfortunately, none of the assessed biomarkers differentiated between tumor types studied, suggesting that the severity of nitrosative damage and inflammation are similar in patients with incidentaloma, pheochromocytoma, and Cushing's or Conn's adenoma. CONCLUSION: Adrenal tumors are associated with increased protein nitration/S-nitrosylation and inflammation.

Skin Substitute Preparation Method Induces Immunomodulatory Changes in Co-Incubated Cells through Collagen Modification.

Chronic ulcerative and hard-healing wounds are a growing global concern. Skin substitutes, including acellular dermal matrices (ADMs), have shown beneficial effects in healing processes. Presently, the vast majority of currently available ADMs are processed from xenobiotic or cadaveric skin. Here we propose a novel strategy for ADM preparation from human abdominoplasty-derived skin. Skin was processed using three different methods of decellularization involving the use of ionic detergent (sodium dodecyl sulfate; SDS, in hADM 1), non-ionic detergent (Triton X-100 in hADM 2), and a combination of recombinant trypsin and Triton X-100 (in hADM 3). We next evaluated the immunogenicity and immunomodulatory properties of this novel hADM by using an in vitro model of peripheral blood mononuclear cell culture, flow cytometry, and cytokine assays. We found that similarly sourced but differentially processed hADMs possess distinct immunogenicity. hADM 1 showed no immunogenic effects as evidenced by low T cell proliferation and no significant change in cytokine profile. In contrast, hADMs 2 and 3 showed relatively higher immunogenicity. Moreover, our novel hADMs exerted no effect on T cell composition after three-day of coincubation. However, we observed significant changes in the composition of monocytes, indicating their maturation toward a phenotype possessing anti-inflammatory and pro-angiogenic properties. Taken together, we showed here that abdominoplasty skin is suitable for hADM manufacturing. More importantly, the use of SDS-based protocols for the purposes of dermal matrix decellularization allows for the preparation of non-immunogenic scaffolds with high therapeutic potential. Despite these encouraging results, further studies are needed to evaluate the beneficial effects of our hADM 1 on deep and hard-healing wounds.

Training in intraoperative neuromonitoring of recurrent laryngeal nerves reduces the risk of their injury during thyroid surgery.

INTRODUCTION: Even though incidence of recurrent laryngeal nerve palsy (RLNP) is low, it affects importantly the quality of life of patients and remains one of main medicolegal litigation problems in surgery. Intraoperative neuromonitoring (IONM) has become widely accepted tool helping in recurrent laryngeal nerve identification, however no clear association of IONM with RLNP rate has been demonstrated. The aim of our study was to assess whether training in IONM influences rates of RNLP after thyroid surgery as an independent factor. MATERIAL AND METHODS: We analysed retrospectively 1235 patients who underwent thyroidectomy at the 1st Department of General and Endocrine Surgery, Medical University of Bialystok. Possible risk factors for RLNP were evaluated: application or not of IONM, the extent of surgery or thyroid pathology in correlation with surgeons' experience in IONM (trained or untrained). RESULTS: There were 2351 nerves at risk (NAR) and 39 RNLP were diagnosed after thyroid surgery (1.66%). Surgeons trained in IONM performed 52.2% of all operations (1200 NAR) with 7 RLNP (0.58%), whereas not-trained had 32 RLNP for 1151 NAR (2.8%; p < 0.001). After 182 thyroidectomies (357 NAR) guided by IONM (14.7%) 3 RLNP were observed (0.84%) vs. 36 palsies per 1994 NAR without IONM (1.81%; p = 0.189). The highest danger of RLNP was reported after reoperations and the lowest after subtotal thyroidectomies. We found no association between thyroid pathology and RLNP rate. CONCLUSIONS: According to our study training in IONM decreases chances of RLNP especially during total or near total thyroidectomy.

Effects of age and gender on the redox homeostasis of morbidly obese people.

Obesity is a chronic disease of complex etiology. Recent evidence suggests that obesity is caused by inflammation of adipose tissue leading to metabolic disorders, cardiovascular disease and cancer. This is the first study to evaluated the effects of age and gender on redox homeostasis, glutathione metabolism, and oxidative damage to plasma/serum lipids and proteins in morbidly obese patients. The study included 120 (60 men and 60 women) morbidly obese patients with class 3 obesity (BMI > 40 kg/m2), classified into three groups depending on age: 20-39 years (n = 20), 40-59 years (n = 20) and 60 years or older (n = 20). The number of patients was calculated a priori based on our previous experiment. We observed a reduction in serum activity of antioxidant enzymes (↓SOD) and plasma concentration of non-enzymatic antioxidants (↓GSH) in obese patients compared to the lean controls, which further decreased with age. Redox status (↑TAC, ↑TOS and ↓OSI) in morbidly obese men and women was shifted towards oxidation. Moreover, lipid (↑MDA and ↑LOOH) and protein (↑AOPP, ↑AGE and ↑Amadori products) damage products of oxidation and nitrosylation/nitration (↑total NO, ↑S-nitrosothiols, ↑peroxynitrite and ↑nitrotyrosine) were elevated in both genders of morbidly obese patients and were higher in the elderly. Interestingly, the concentrations of oxidative and nitrosative stress markers were generally higher in obese men compared to obese women at the same age. Summarizing, we showed that the total antioxidant/oxidant potential of obese patients is significantly increased and shifted towards oxidation. Obese patients have increased lipid and protein oxidation, glycation and nitration as compared to the lean controls. Disturbances in redox homeostasis increase with age in obese patients. Oxidative and nitrosative stress are more intense in men than in women at the same age.

Antioxidant Barrier and Oxidative Damage to Proteins, Lipids, and DNA/RNA in Adrenal Tumor Patients.

This study is the first to assess redox balance, glutathione metabolism, and oxidative damage to RNA/DNA, proteins, and lipids in the plasma/serum and urine of patients with adrenal masses. The study included 70 patients with adrenal tumors divided into three subgroups: incidentaloma (n = 30), pheochromocytoma (n = 20), and Cushing's/Conn's adenoma (n = 20), as well as 60 healthy controls. Blood and urine samples were collected before elective endoscopic adrenalectomy. Antioxidant defense capacity was significantly decreased (serum/plasma: superoxide dismutase (SOD), catalase (CAT) and reduced glutathione (GSH), uric acid (UA); urine: SOD, GSH, UA) in patients with adrenal masses. The oxidative damage to proteins (advanced glycation end products (AGE), advanced oxidation protein products (AOPP)) and lipids (lipid hydroperoxides (LOOH), and malondialdehyde (MDA)) was higher in the plasma and urine of these patients. Plasma MDA and DNA/RNA oxidation products, with high sensitivity and specificity, can help to diagnose pheochromocytoma. This biomarker differentiates patients with pheochromocytoma from Cushing's/Conn's adenoma as well as from heathy controls. Plasma RNA/DNA oxidation was also positively correlated with urine metanephrine. Oxidative stress can play a crucial role in adrenal tumors. However, further studies are required to clarify the role of redox signaling in adrenal masses.

Bariatric Surgery Normalizes Protein Glycoxidation and Nitrosative Stress in Morbidly Obese Patients.

The results of recent studies indicate the key role of nitrosative stress and protein oxidative damage in the development of morbid obesity. Nevertheless, the effect of bariatric surgery on protein oxidation/glycation and nitrosative/nitrative stress is not yet known. This is the first study evaluating protein glycoxidation and protein nitrosative damage in morbidly obese patients before and after (one, three, six and twelve months) laparoscopic sleeve gastrectomy. The study included 50 women with morbid obesity as well as 50 age- and gender-matched healthy controls. We demonstrated significant increases in serum myeloperoxidase, plasma glycooxidative products (dityrosine, kynurenine, N-formyl-kynurenine, amyloid, Amadori products, glycophore), protein oxidative damage (ischemia modified albumin) and nitrosative/nitrative stress (nitric oxide, peroxy-nitrite, S-nitrosothiols and nitro-tyrosine) in morbidly obese subjects as compared to lean controls, whereas plasma tryptophan and total thiols were statistically decreased. Bariatric surgery generally reduces the abnormalities in the glycoxidation of proteins and nitrosative/nitrative stress. Noteworthily, in the patients with metabolic syndrome (MS+), we showed no differences in most redox biomarkers, as compared to morbidly obese patients without MS (MS-). However, two markers: were able to differentiate MS+ and MS- with high specificity and sensitivity: peroxy-nitrite (>70%) and S-nitrosothiols (>60%). Further studies are required to confirm the diagnostic usefulness of such biomarkers.

The Impact of Hypertension and Metabolic Syndrome on Nitrosative Stress and Glutathione Metabolism in Patients with Morbid Obesity.

In this pathbreaking study, we evaluated nitrosative stress in morbidly obese patients with and without metabolic syndrome. 62 women with class 3 obesity (BMI > 40 kg/m2) were divided into three subgroups: obese patients (OB), obese patients with hypertension (OB+HYP), and obese patients with metabolic syndrome (OB+MS). In comparison to the lean patients, OB had increased levels of serum myeloperoxidase (MPO), plasma nitric oxide (NO), S-nitrosothiols, and peroxynitrite (ONOO-), as well as nitrotyrosine, while oxidized glutathione (GSSG) rose only in OB+HYP group. Interestingly, ONOO- was significantly higher in OB+HYP and OB+MS as compared to OB group, while MPO only in OB+MS group. OB+MS had greater nitrotyrosine and S-nitrosothiol values than OB+HYP. Moreover, peroxynitrite could differentiate OB from OB+HYP and OB+MS (AUC 0.9292; p < 0.0001; 87.5% sensitivity, 90% specificity) as well as between OB and OB+MS group (AUC 0.9125; p < 0.0001; 81.25% sensitivity, 83.33%). In conclusion, we showed that MPO activity, NO formation, and nitrosative damage to proteins parallel the progression of metabolic disturbances of obesity. Evaluation of ONOO- concentrations may help predict the development of hypertension and metabolic syndrome in patients with morbid obesity; however, longer-term studies are required for larger numbers of patients.

Markers of metastatic colorectal cancer.

Metastatic colorectal cancer (CRC) is a major cause of cancer-related death. However, early diagnosis of CRC metastases offers a chance of long-term survival in as much as 40% of patients after curative treatment. Current guidelines are based on clinical examination, carcinoembryonic antigen (CEA) testing, computed tomography scanning, and endoscopic surveillance. Although CEA is the most widely used laboratory test, it has very low sensitivity (30-40%). Moreover, there is no evidence to support the association of CEA testing with improved survival or quality of life. Thus, novel markers with greater specificity and sensitivity are needed. The aim of this review was to define the role of available laboratory markers in early diagnosis of metastatic CRC. We identified novel tests with the highest association to metastatic CRC: circulating tumour DNA, growth/differentiation factor 15, and ß6-integrin. We also discuss other promising markers, although most of the studies are preliminary and require validation.

Impact of Weight Loss on the Total Antioxidant/Oxidant Potential in Patients with Morbid Obesity-A Longitudinal Study.

The assessment of total antioxidant activity seems to have a higher diagnostic value than the evaluation of individual antioxidants separately. Therefore, this is the first study to assess the total antioxidant/oxidant status in morbidly obese patients undergoing bariatric surgery. The study involved 60 patients with Class 3 obesity (BMI > 40 kg/m2) divided into two equal subgroups: morbidly obese patients without and with metabolic syndrome. The analyses were performed in plasma samples collected before surgery as well as 1, 3, 6, and 12 months after a laparoscopic sleeve gastrectomy. Total antioxidant capacity (TAC), ferric-reducing antioxidant power (FRAP), DPPH (2,2'-diphenyl-1-picrylhydrazyl) radical assay, and total oxidant status (TOS) were significantly higher before surgery (as compared to the healthy controls, n = 60) and generally decreased after bariatric treatment. Interestingly, all assessed biomarkers correlated positively with uric acid content. However, the total antioxidant/oxidant potential did not differ between obese patients without metabolic syndrome and those with both obesity and metabolic syndrome. Only DPPH differentiated the two subgroups (p < 0.0001; AUC 0.8) with 73% sensitivity and 77% specificity. Plasma TAC correlated positively with body mass index, waist-hip ratio, serum insulin, and uric acid. Therefore, TAC seems to be the best biomarker to assess the antioxidant status of obese patients.

A Longitudinal Study of the Antioxidant Barrier and Oxidative Stress in Morbidly Obese Patients after Bariatric Surgery. Does the Metabolic Syndrome Affect the Redox Homeostasis of Obese People?

This is the first study to evaluate both the antioxidant barrier, glutathione metabolism, and oxidative damage to proteins and lipids in morbidly obese patients undergoing bariatric treatment. The study included 65 patients with class 3 obesity divided into two subgroups: morbidly obese patients without metabolic syndrome (OB) and obese patients with metabolic syndrome (OB + MS). Blood samples were collected before surgery as well as one, three, six, and twelve months after the bariatric treatment. Superoxide dismutase and reduced glutathione (GSH) were significantly decreased, whereas glutathione reductase and uric acid were enhanced in morbidly obese patients before bariatric surgery as compared to lean control. Moreover, in the OB group, we observed the increase of superoxide dismutase (SOD) and the decrease of uric acid (UA) after the bariatric treatment; however, these changes were not observed in the OB + MS group. The oxidative damage to proteins (advanced glycation end products, AGE; advanced oxidation protein products, AOPP) and lipids (8-isoprostanes, 8-isop; 4-hydroxynoneal) was higher in OB as well as OB + MS patients. We noticed that AGE and AOPP levels diminished after the bariatric treatment, whereas redox status (ratio of GSH to oxidized glutathione) was still reduced in the OB + MS group. Summarizing, morbid obesity is associated with disturbances in the antioxidant barrier and enhanced oxidative damage to proteins and lipids. Although bariatric surgery improves redox homeostasis in obese patients, those with metabolic syndrome show a continuous decrease in the antioxidant status. In patients undergoing bariatric treatment, antioxidant supplementation may be considered.

Laparoscopic sleeve gastrectomy: a study of efficiency in treatment of metabolic syndrome components, comorbidities and influence on certain biochemical markers.

INTRODUCTION: The worldwide outbreak of morbid obesity forced contemporary medicine to adopt a multidisciplinary approach, which led to the description of metabolic syndrome (MS): a disease with self-aggravating components and one of the most important causes of morbidity and mortality. The need for therapeutic methods provoked development of metabolic surgery, which nowadays give possibilities for safe and effective treatment of all MS aspects simultaneously and improves many obesity-related comorbidities. AIM: To assess the laparoscopic sleeve gastrectomy (LSG) procedure's efficiency in resolving MS components, treating comorbidities and to analyze the influence on certain biochemical markers in 1-year follow-up. MATERIAL AND METHODS: The retrospective cohort study of 211 patients after an LSG operation relied on statistical analysis of clinical data collected prospectively in follow-up visits. All applicable guidelines and bioethical recommendations were respected in this study. RESULTS: Assessment of bariatric efficiency proved the LSG operation to be effective in inducing significant weight loss and treating obesity. Analysis on the influence on MS components, such as non-insulin dependent diabetes (NIDDM), arterial hypertension (AH) and dyslipidemia, showed substantial improvement in all observed cases of these diseases. In the present study, follow-up also proved a partial remission inducing effect of this bariatric operation in many comorbidities, especially in chronic obstructive pulmonary disease, obstructive sleep apnea, peptic ulcer disease and depression. A desirable reduction in creatinine, C-reactive protein, uric acid, alanine aminotransferase, asparagine aminotransferase, γ-glutamyltransferase serum levels has also been observed during the follow-up. CONCLUSIONS: The LSG is an effective method of treatment in all areas of metabolic syndrome, provides a significant positive clinical outcome in obesity-related comorbidities and induces desirable changes in inflammatory, kidney and liver related biomarkers.

Gender-related metabolic outcomes of laparoscopic sleeve gastrectomy in 6-month follow-up.

INTRODUCTION: Laparoscopic sleeve gastrectomy (LSG) is recently a leading method in surgical treatment of morbid obesity. The metabolic outcome of intervention may be a result of many factors such as age, gender, preoperative weight loss and dietary restrictions. AIM: To evaluate gender-related differences in the results of LSG in 6-month follow-up. MATERIAL AND METHODS: The study included 101 patients who underwent LSG at the University Clinical Hospital of Bialystok. Patients were divided and analyzed in 2 groups: males (n = 48) and females (n = 53). The primary analysis included the influence of gender on postoperative weight loss calculated using the percentage of excess weight loss (%EWL) and excess BMI loss (%EBMIL). For secondary outcomes the levels of glucose, insulin, glycated hemoglobin, aspartate transaminase, alanine transaminase, total cholesterol, high-density lipoprotein (HDL), low-density lipoprotein (LDL), triglycerides and C-reactive protein were analyzed. RESULTS: A significant influence of patients' gender was proved for both %EWL (p = 0.026) and %EBMIL (p = 0.001). Females had significantly higher %EWL in 6-month follow-up than males (p = 0.0034). The analysis also showed significantly higher %EBMIL for women at 3 and 6 months observation (p = 0.022 and p < 0.001 respectively). CONCLUSIONS: Laparoscopic sleeve gastrectomy is an effective method of obesity treatment especially in terms of postoperative weight loss. Females seem to benefit more from the procedure when analyzing the parameters of body mass reduction. However, further research is needed to provide strong evidence of an association between gender and the results of LSG.

Ceramide Content in Liver Increases Along with Insulin Resistance in Obese Patients.

The liver plays a central role in the glucose and lipid metabolism. Studies performed on animal models have shown an important role of lipid accumulation in the induction of insulin resistance. We sought to explain whether in obese humans, the insulin resistance is associated with hepatic ceramide accumulation. The experiments were conducted on obese men and women. Each gender was divided into three groups: Normal glucose tolerance group (NGT), Impaired glucose tolerance group (IGT), and Type 2 diabetic subjects (T2D). Ceramide (Cer) content was analyzed with the use of LC/MS/MS. An oral glucose tolerance test (OGTT), glycosylated hemoglobin (HbA1c), percentage body fat (FAT%), and body mass index (BMI) was also measured. Total hepatic ceramide was significantly higher in T2D females as compared to NGT females (p < 0.05), whereas in males, total ceramide was significantly higher in IGT and T2D as compared to NGT (p < 0.05). In both, men and women, the highest increase in T2D subjects, was observed in C16:0-Cer, C18:0:-Cer, C22:0-Cer, and C24:0-Cer (p < 0.05) as compared to NGT group. Interestingly, glucose (at 0' and at 120' in OGTT) and HbA1c positively correlated with the ceramide species that most increased in T2D patients (C16:0-Cer, C18:0-Cer, C22:0-Cer, and C24:0-Cer). In men glucose and HbA1c significantly correlated with only C22:0-Cer. This is one of the few studies comparing hepatic ceramide content in severely obese patients. We found that, ceramide content increased in diabetic patients, both in men and women, and the content of ceramide correlated with glycemic parameters. These data indicate ceramide contribution to the induction of hepatic insulin resistance.

The impact of laparoscopic adrenalectomy on renal function. Results of a prospective randomised clinical trial.

INTRODUCTION: Laparoscopic adrenalectomy is the gold standard management of benign adrenal masses and isolated metastases to adrenal glands. Two techniques of endoscopic adrenalectomy: lateral transperitoneal approach (LTA) and posterior retroperitoneal approach (PRA) seem to be equally safe and effective. Recent studies suggest advantages of PRA over LTA in terms of lower intensity of postoperative pain, shorter hospital stay, faster recovery, and lower early morbidity. However, PRA involves high insufflation pressure of CO2 within a limited retroperitoneal space. The aim of our study was to prospectively assess the effect of LTA versus PRA laparoscopic adrenalectomies on renal function. MATERIAL AND METHODS: We randomly assigned patients referred for unilateral adrenalectomy to either LTA (n = 33) or PRA (n = 44). The inclusion criteria were: hormonal activity and/or tumour diameter > 4 cm and/or suspicion of metastasis to adrenal gland. The exclusion criteria comprised: tumours > 8 cm, results of imaging studies suggesting primary invasive malignancy, and refusal to undergo randomisation. The patients were prospectively followed for a minimum of six months. Serum creatinine, cystatin C, and urinary neutrophil gelatinase-associated lipocalin (NGAL) were measured preoperatively and at postoperative days: 1, 7, and 30. RESULTS: We found increased concentrations of urinary NGAL at day 1 following laparoscopic adrenalectomy using PRA, as compared to LTA. Patients undergoing right-sided PRA had increased creatinine concentrations, as compared to left-sided PRA. Patients with aldosterone-producing adenoma had decreased preoperative eGFR as compared to subjects with non-functioning incidentaloma. NGAL increased significantly in this group postoperatively. All the disturbances normalised within one month postoperatively. CONCLUSIONS: Renal function impairment after PRA may result from compression of inferior vena cava by high retroperitoneal pressure during right-sided adrenalectomy. Despite the transient character of the observed abnormalities, we suggest that patients with high risk of acute kidney injury may benefit from an alternative technique of adrenalectomy using LTA.

Laparoscopic adrenalectomy: lateral transperitoneal versus posterior retroperitoneal approach - prospective randomized trial.

INTRODUCTION: Laparoscopic adrenalectomy has become the gold standard of surgical treatment for benign adrenal masses. Two alternative surgical approaches are currently advocated: the lateral transperitoneal approach (LTA) and the posterior retroperitoneal approach (PRA). Several randomized trials have compared LTA to PRA, but most of them included small numbers of patients or had stringent inclusion criteria. AIM: To compare clinical results of LTA and PRA endoscopic adrenalectomies for tumors < 8 cm with wide inclusion criteria. MATERIAL AND METHODS: We randomized 77 patients to either LTA (n = 33) or PRA (n = 44). The groups were comparable in terms of age, gender proportions, body mass index, tumor size, clinical and pathological diagnosis. We analyzed duration of surgery, intraoperative blood loss, postoperative pain, length of hospital stay and postoperative morbidity. RESULTS: The follow-up concerned 98.8% of patients and was on average 28 (8-47) months long. There were no conversions. We identified significantly lower intensity of pain assessed 24 h after surgery in the PRA group (3.4 ±1), as compared to LTA (4.2 ±1), with lower prevalence of shoulder pain (2.3% vs. 30.3%, respectively). Postoperative hospital stay was shorter in the PRA (1.14 ±0.4) than in the LTA (1.36 ±0.5) group. Perioperative morbidity concerned 4 patients in each group with pain requiring oral analgesia > 7 days. CONCLUSIONS: To our knowledge this is the largest prospective randomized study comparing LTA to PRA. We demonstrated safety, efficacy and very low morbidity of both techniques. The PRA proved superior to LTA in terms of lower intensity of postoperative pain and shorter hospital stay.

Metabolic Syndrome is Associated with Ceramide Accumulation in Visceral Adipose Tissue of Women with Morbid Obesity.

OBJECTIVE: Accelerated transmembrane transport of long-chain fatty acids dependent on fatty acid transporters is responsible for lipid accumulation and, eventually, the development of metabolic syndrome. This study determined the content of lipids (ceramide [CER], diacylglycerol [DAG], triacylglycerol, and free fatty acid [FFA]) and the expression of fatty acid translocase (FAT/CD36) and plasma membrane fatty acid-binding protein in visceral adipose tissue (VAT) and subcutaneous adipose tissue of women with morbid obesity without metabolic syndrome (MetSx-) or with metabolic syndrome (MetSx+) and compared the results with those of lean controls without metabolic syndrome. METHODS: Lipid content and fatty acid composition in each lipid subclass were estimated by gas liquid chromatography. For total, plasma membrane, and mitochondrial expression of fatty acid transporters, subfractionation with subsequent Western blot technique was used. RESULTS: A greater content of triacylglycerol in VAT of participants with obesity (MetSx-) was found. However, only the MetSx+ subjects had increased content of CER in VAT in relation to subcutaneous adipose tissue in MetSx+ and lean individuals. This was accompanied by increased total and membrane expression of FAT/CD36 in VAT in MetSx+ subjects. Accordingly, mitochondrial expression of FAT/CD36 and plasma membrane fatty acid-binding protein was decreased in both groups of subjects with obesity. CONCLUSIONS: Metabolic syndrome is associated with the accumulation of CER in VAT, possibly related to increased FAT/CD36 protein expression.

Gastric band migration to gastrointestinal lumen and possibilities of its surgical treatment.

BACKGROUND: Due to numerous late complications after laparoscopic adjustable gastric banding (LAGB), leading to band removal, a significant decrease of its application has been observed. OBJECTIVES: The objective of this study was to present complications after LAGB in our own material. MATERIAL AND METHODS: The study included 152 obese patients who underwent LAGB between 2005 and 2012. The group of women consisted of 91 patients (60%) with the following preoperative parameters: average body mass index (BMI) 42 ±3.66 kg/m2 and average body mass 122 ±12.8 kg. The group of men included 61 patients (40%) with a preoperative average BMI 43 ±3.81 kg/m2 and average body mass 125 ±13.02 kg. The average age of women was 35.02 ±11.6 years and of men 36.18 ±10.5 years. RESULTS: Among 152 patients after LAGB due to morbid obesity, in 7 (4.6%) migration of the band to the stomach lumen was observed, in 4 port wound purulence occurred, in 3 stomach mucosa ulceration was diagnosed in the band pressure area, 3 reported heartburn and hyperacidity, and 4 suffered from emesis. In all aforementioned patients, body mass loss stopped and they reported lack of restriction after last band regulation. CONCLUSIONS: Surgical or endoscopic treatment in patients with a migrated band is an individual matter depending on the type and size of band dislocation, its clinical symptoms and the general state of the patient, but also on the experience of the operating team and the quality of the equipment.