Oncogenic osteomalacia - detection of the tumour site upon physical examination.

Not required for Clinical Vignette.

Changes in the Serum Fatty Acid Profile After Anhepatic Phase of Orthotopic Liver Transplantation Procedure.

During orthotopic liver transplantation (OLT), the patients' body remains deprived of this organ for some time, which could cause critical changes in the levels of various metabolites in the circulation, including fatty acids. Thus, the aim of this study was to determine whether the liver transplantation procedure leads to significant changes in the FA profile in serum lipids after the anhepatic phase. Our gas chromatography-mass spectrometry analysis revealed that after transplantation, serum levels of myristic and palmitic acids significantly decreased, whereas serum levels of very long-chain FAs containing 20 or more carbons in their chains were increased. These results indicate that the anhepatic phase during liver transplantation produces significant changes in serum fatty acid levels, and emphasizes the role of the liver in the metabolism of very long-chain fatty acids.

Serum free fatty acid levels and insulin resistance in patients undergoing one-anastomosis gastric bypass.

INTRODUCTION: One anastomosis gastric bypass (OAGB) leads to improvement in glucose homeostasis; however, the mechanism of this beneficial effect is not fully understood. Increased serum free fatty acid (FFA) concentrations in obese subjects contribute to the development of insulin resistance and type 2 diabetes. AIM: The authors hypothesized that improvement in glucose homeostasis after OAGB may be associated with a decrease in FFA concentration. MATERIAL AND METHODS: Serum FFA levels were measured by gas chromatography-mass spectrometry before and 3 months after OAGB and, for comparison, in patients who underwent laparoscopic sleeve gastrectomy (LSG). Serum insulin was assayed by immunoenzymatic method, and other parameters by standard laboratory methods. RESULTS: OAGB resulted in a large decrease in FFA levels and great improvement in insulin sensitivity. These effects in patients after LSG were less prominent. CONCLUSIONS: Results suggest that decreased serum FFA levels after OAGB contribute to resolution of insulin sensitivity after this type of bariatric surgery.

The Impact of Kidney Transplantation on the Serum Fatty Acid Profile in Patients with End-Stage Kidney Disease.

Epidemiological data indicate that metabolic disturbances and increased cardiovascular risk in renal transplant patients are a significant and common problem. Therefore, it is important to search for new solutions and, at the same time, counteract the negative effects of currently used therapies. In this study, we examined the effect of kidney transplantation on the serum levels of fatty acids (FAs) in order to assess the role of these compounds in the health of transplant patients. The FA profile was analyzed by gas chromatography-mass spectrometry in the serum of 35 kidney transplant recipients, just before transplantation and 3 months later. The content of total n-3 polyunsaturated FAs (PUFAs) decreased after transplantation (3.06 ± 0.13% vs. 2.66 ± 0.14%; p < 0.05). The total amount of ultra-long-chain FAs containing 26 and more carbon atoms was significantly reduced (0.08 ± 0.009% vs. 0.05 ± 0.007%; p < 0.05). The desaturation index (18:1/18:0) increased after transplantation (3.92 ± 0.11% vs. 4.36 ± 0.18%; p < 0.05). The study showed a significant reduction in n-3 PUFAs in renal transplant recipients 3 months after transplantation, which may contribute to increased cardiovascular risk in this patient population.

"Old School" Islet Purification Based on the Unit Gravity Sedimentation as a Rescue Technique for Intraportal Islet Transplantation-A Case Report.

Here, we present a case that required a supplemental "old school" islet purification for a safe intraportal infusion. Following pancreas procurement from a brain-dead 26-year-old male donor (body mass index: 21.9), 24.6 ml of islet tissue was isolated after continuous density gradient centrifugation. The islet yield was 504,000 islet equivalent (IEQ), distributed among the following three fractions: 64,161 IEQ in 0.6 ml of pellet, 182,058 IEQ in 10 ml, and 258,010 IEQ in 14 ml with 95%, 20%, and 10% purity, respectively. After a 23-h culture, we applied supplemental islet purification, based on the separation of tissue subfractions during unit gravity sedimentation, a technique developed over 60 years ago ("old school"). This method enabled the reduction of the total pellet volume to 11.6 ml, while retaining 374,940 IEQ with a viability of over 90%. The final islet product was prepared in three infusion bags, containing 130,926 IEQ in 2.6 ml of pellet, 108,079 IEQ in 4 ml of pellet, and 135,935 IEQ in 5 ml of pellet with 65%, 40%, and 30% purity, respectively, and with the addition of unfractionated heparin (70 units/kg body weight). Upon the islet infusion from all three bags, portal pressure increased from 7 to 16 mmHg. Antithrombotic prophylaxis with heparin was continued for 48 h after the infusion, with target activated partial thromboplastin time 50-60 s, followed by fractionated heparin subcutaneous injections for 2 weeks. ß-Cell graft function assessed on day 75 post-transplantation was good, according to Igls criteria, with complete elimination of severe hypoglycemic episodes and 50% reduction in insulin requirements. Time spent within the target glucose range (70-180 mg/dl) improved from 42% to 98% and HbA1c declined from 8.7% to 6.7%. Supplemental "old school" islet purification allowed for the safe and successful utilization of a robust and high-quality islet preparation, which otherwise would have been discarded.

Increased Expression of the Leptin Gene in Adipose Tissue of Patients with Chronic Kidney Disease-The Possible Role of an Abnormal Serum Fatty Acid Profile.

Chronic kidney disease (CKD) is associated with an increased level of leptin and an abnormal fatty acid (FA) profile in the serum. However, there are no data on the associations between them, and the reason for increased serum levels in patients with CKD is not well elucidated. Recently, we found that a CKD-related abnormal FA profile caused significant changes in the expression of genes involved in lipid metabolism in hepatocytes. The aim of this study was to examine whether leptin gene expression in subcutaneous adipose tissue (SAT) of patients with CKD may contribute to increased serum levels of this adipokine and whether the abnormal serum FA profile observed in CKD patients has an impact on leptin gene expression in adipocytes. The FA profile was measured in serum samples from patients with CKD and controls by GC-MS. The relative mRNA levels of leptin were measured in SAT by Real-Time PCR. Moreover, the effect of the CKD-related abnormal FA profile on leptin gene expression was studied in in vitro cultured 3T3-L1 adipocytes. Patients with CKD had higher concentrations of serum leptin than controls and higher expression level of the leptin gene in SAT. They also had increased serum monounsaturated FAs and decreased polyunsaturated FAs. The incubation of adipocytes with FAs isolated from CKD patients resulted in an increase of the levels of leptin mRNA. Increased leptin gene expression in SAT may contribute to elevated concentrations of these adipokine in patients with CKD. CKD-related alterations of the FA profile may contribute to elevated serum leptin concentrations in patients with CKD by increasing the gene expression of this adipokine in SAT.

Medullary thyroid carcinoma of unknown primary origin with synchronous finding of papillary thyroid carcinoma.

Not required for Clinical Vignette.

Metabolic pathway of 4-pyridone-3-carboxamide-1ß-d-ribonucleoside and its effects on cellular energetics.

4-pirydone-3-carboxamide-1ß-d-ribonucleoside (4PYR) is an endogenous nucleoside that could be converted to triphosphates, diphosphates, monophosphates and an analogue of NAD - 4PYRAD. Elevated level of these compounds have been reported in chronic renal failure, cancer and active HIV infection. However, little is known about the effect on cell functionality and the metabolic pathways. This study tested effects of 4PYR in different cell types on nucleotide, energy metabolism and clarified enzymes that are involved in conversions of 4PYR. We have found that human neuroblastoma cells, human malignant melanoma cells, human adipose-derived stem cells, human bone marrow-derived stem cells, human dermal microvascular endothelial cells and human embryonic kidney cells, were capable to convert 4PYR into its derivatives. This was associated with deterioration of cellular energetics. Incubation with 4PYR did not affect mitochondrial function, but decreased glycolytic rate (as measured by extracellular acidification) in endothelial cells. Silencing of adenosine kinase, cytosolic 5'-nucleotidase II and nicotinamide nucleotide adenylyltransferase 3, blocked metabolism of 4PYR. Incubation of endothelial cells with 4PYR decreased AMP deaminase activity by 40%. The main finding of this paper is that human cells (including cancer type) are capable of metabolizing 4PYR that lead to deterioration of energy metabolism, possibly as the consequence of inhibition of glycolysis. This study, it was also found that several enzymes of nucleotide metabolism could also contribute to the 4PYRconversions.

Comparison of perioperative stress in patients undergoing thyroid surgery with and without neuromonitoring-a pilot study.

PURPOSE: A comprehensive psychological comparison of preoperative stress in patients scheduled for thyroidectomy with versus without intraoperative neurophysiologic monitoring (IONM) has never been reported. The aim of this study was to assess whether a planned utilization of IONM had any effect on the reduction of stress and anxiety level before and after thyroid surgery. METHODS: The outcomes of 32 patients scheduled for thyroidectomy with IONM were compared to the outcomes of a carefully matched control group of 39 patients operated on without IONM. All the patients were tested before the surgery and at 1-7 days postoperatively employing psychological self-report instruments: the Depression Anxiety Stress Scales (DASS), State-Trait Anxiety Inventory (STAI), 12-item General Health Questionnaire (GHQ), Functional Assessment of Cancer Therapy-Head and Neck Scale (FACT H&N), and the visual analog scale (VAS). RESULTS: The examined groups were homogenous and carefully matched in terms of mental health (GHQ), the quality of life (FACT H&N), and the intensity of depression level (DASS). The IONM group showed a significantly lower level of "the state anxiety"(STAI) 1 day before the operation (p < 0.05), greater trust in the doctor (VAS) (p < 0.05), and greater confidence in the treatment method (VAS) as compared to the patients in the control group (p < 0.05), while no significant differences were found when the remaining items were compared. CONCLUSIONS: The planned use of IONM during thyroidectomy may reduce patient anxiety before surgery. However, further research in this area is necessary to confirm this preliminary finding in a larger population of patients.

A comprehensive study of serum odd- and branched-chain fatty acids in patients with excess weight.

OBJECTIVE: While small amounts of odd-chain fatty acids (OCFAs) and branched-chain fatty acids (BCFAs) were known to be present in mammals, it was quite recently that they were shown to play an important role in human health. However, still little is known on OCFA and BCFA profiles in subjects who have obesity. The aim of this study was to verify whether obesity is associated with changes in serum OCFA and BCFA profiles. METHODS: Serum content of fatty acids was determined by gas chromatography-mass spectroscopy in 23 patients with excess weight and 21 nonobese controls. RESULTS: Six OCFAs and six BCFAs (three iso-BCFAs and three anteiso-BCFAs) were found in sera from the examined subjects. Patients with excess weight presented with significantly lower serum iso-BCFA levels than the controls. Total serum content of iso-BCFAs correlated inversely with serum insulin, triglycerides, and 18:1/18:0 desaturation index. Both OCFA and iso-BCFA levels correlated inversely with C-reactive protein concentration. CONCLUSIONS: Lower iso-BCFA content in patients with excess weight may be involved in elevation of serum concentration of triglycerides and inflammation. Decreased contents of iso-BCFAs in subjects with have obesity, and established anti-inflammatory, antidiabetic, and anticancer properties of these fatty acids, point to potential beneficial effects of an iso-BCFA-rich diet.

Increased Serum Level of Cyclopropaneoctanoic Acid 2-Hexyl in Patients with Hypertriglyceridemia-Related Disorders.

We recently reported the presence of various cyclopropane fatty acids-among them, cyclopropaneoctanoic acid 2-hexyl-in the adipose tissue of obese women. The aim of this study was to verify whether the presence of cyclopropaneoctanoic acid 2-hexyl in human serum was associated with obesity or chronic kidney disease (both being related to dyslipidemia), and to find potential associations between the serum level of this compound and specific markers of the these conditions. The serum concentration of cyclopropaneoctanoic acid 2-hexyl was determined by gas chromatography-mass spectrometry (GC-MS) in non-obese controls, obese patients, obese patients after a 3-month low-calorie diet, and individuals with chronic kidney disease. Obese patients and those with chronic kidney disease presented with higher serum levels of cyclopropaneoctanoic acid 2-hexyl than controls. Switching obese individuals to a low-calorie (low-lipid) diet resulted in a reduction in this fatty acid concentration to the level observed in controls. Cyclopropaneoctanoic acid 2-hexyl was also found in foods derived from animal fat. Serum concentrations of triacylglycerols in the analyzed groups followed a pattern similar to that for serum cyclopropaneoctanoic acid 2-hexyl, and these variables were positively correlated with each other among the studied groups. Patients with hypertriglyceridemia-related conditions presented with elevated serum levels of cyclopropaneoctanoic acid 2-hexyl. Our findings suggest that its high serum level is related to high serum triacylglycerol concentrations rather than to body mass or BMI.

Cerulein-induced acute pancreatitis is associated with c-Jun NH(2)-terminal kinase 1-dependent ferritin degradation and iron-dependent free radicals formation.

OBJECTIVES: The main goal of this work was to get insight into the mechanism of cerulein-induced reactive oxygen species (ROS) formation and impact of c-Jun NH(2)-terminal kinase (JNK) on this process. METHODS: The study was performed on Wistar rats and on a cellular model of acute pancreatitis (AP) using AR42J cell line. RESULTS: First of all, we observed that during AP, the iron storage protein ferritin in the rat pancreas undergoes degradation accompanied by an increased formation of protein carbonyls. Pancreatic acinar AR42J cells stimulated by cerulein showed increased labile iron pool that was accompanied by a decrease in the cellular ferritin-L level and an increase in the ROS formation. The changes in the ferritin-L level were inversely correlated with the ROS formation. The cells expressing inactive JNK1 mutant were completely resistant to cerulein-induced ferritin degradation. CONCLUSIONS: Our data showed that cerulein-induced AP in rats and on cellular model is accompanied by JNK1-dependent ferritin degradation, increases labile iron pool and ROS formation.