The relationship between sarcopenia and serum irisin and TNF-α levels in newly diagnosed cancer patients.

OBJECTIVE: Sarcopenia in patients with cancer makes patients physically weak and adversely affects their compliance with treatment. In this study, we investigated the relationship between sarcopenia in patients with cancer and circulating irisin and tumor necrosis factor-alpha (TNF-α) levels. MATERIAL AND METHOD: A total of 141 patients with different types of newly diagnosed cancer were divided into two groups, sarcopenia (n = 72) and non-sarcopenia (n = 69) groups. The body compositions of the patients were measured using bioelectrical impedance (BIA) and muscle strength using hand grip strength (HGS) tests. Serum irisin and TNF-α levels were measured using an enzyme-linked immunosorbent assay. RESULTS: In our study, serum irisin levels were found to be significantly lower (p < 0.01) and TNF-α levels were found to be significantly higher (p = 0.014) in the sarcopenia group. Skeletal muscle index (SMI) and HGS values and serum irisin levels were positively correlated [(r: 0.451, p < 0.001), (r: 0.469, p < 0.001)], and SMI and HGS values and serum TNF-α levels were negatively correlated [(r: -0.181, p = 0.032) and (r: -0.143, p = 0.090), respectively]. In addition, multiple linear regression analysis showed that serum irisin and TNF-α levels were independent predictors of sarcopenia. CONCLUSION: Serum irisin levels were found to be significantly lower in patients with cancer with sarcopenia, and TNF-α levels were found to be significantly higher. These two markers can be used as potential biomarkers for the diagnosis of sarcopenia in patients with cancer. The efficacy and possible mechanisms of action of irisin and TNF-α in the diagnosis of sarcopenia should be investigated with larger patient groups.

Presence of macroproteins on the measurement of vitamin B12: studying high vitamin B12 levels using polyethylene glycol and heterophile antibody blocking tubes.

Immune methods are measurement systems that can be affected by interference. The interfering substance may be endogenous immunoglobulins, antibodies, analyte-antibody complexes, and heterophile antibodies. In our study, we aimed to investigate the effect of macrovitamin B12 on high vitamin B12 levels measured using immune methods. Among the serum samples studied in our laboratory; serum from 145 individuals was determined as the patient group and serum from 50 individuals was determined as the control group. We investigated the effect of macroprotein on B12 measurement by using polyethylene glycol (PEG) precipitation, heterophile antibody blocking tube (HBT) and serial dilution methods. According to the recovery evaluation and the modified reference range evaluation after precipitation with PEG, the macrovitamin B12 percentage in the patient group was 58 (40%) and 65 (44.8%), respectively. There was no decrease in vitamin B12 values after the study with HBT. A lack of linearity was observed in 23 (18.7%) of 123 sera with serial dilution method. Macrovitamin B12 should be considered as a differential diagnosis of unexpectedly high vitamin B12 levels. According to the results of our study, we think that it would be appropriate to precipitate with PEG first when there is a suspicion of macrovitamin B12. In collaboration with clinical and laboratory, we recommend that the patient's clinical status and additional laboratory findings be examined, and the patient's sample should be evaluated and interpreted by a specialist in biochemistry by selecting the appropriate interference detection method.

Associations Between Bioavailable Vitamin D and Remnant Cholesterol in Patients With Type 2 Diabetes Mellitus.

Introduction In circulation, 99% vitamin D is transported by binding to vitamin D binding protein (VDBP) and albumin. Vitamin D at free form and vitamin D binding to albumin are defined as bioavailable vitamin D. Vitamin D deficiency is associated with atherogenic lipid profile and insulin resistance. Remnant cholesterol is defined as the cholesterol component of triglyceride-rich lipoproteins and contributes to the atherosclerotic burden. The aim of this study was to investigate the association between bioavailable vitamin D and remnant cholesterol in patients with type 2 diabetes mellitus (T2DM). Methods A total of 198 T2DM patients and 208 non-diabetic subjects underwent biochemical measurements of lipid profiles, 25(OH)D, VDBP, CRP and albumin levels. Their demographic characteristics (age, sex) were questioned. Subjects with thyroid, kidney and liver dysfunction and using lipid-lowering therapy were not included in the study. The diagnosis of T2DM was made according to the American Diabetes Association ADA 2016 criteria. Classification of vitamin D levels was done according to the Endocrine Society. Bioavailable vitamin D concentrations were calculated. Results High-density lipoprotein cholesterol (HDL), 25(OH)D, free vitamin D and bioavailable vitamin D levels were significantly lower in diabetic patients than in non-diabetic patients while triglyceride, remnant cholesterol and CRP levels were found to be significantly higher. VDBP was positively correlated with CRP and remnant cholesterol in diabetic patients, but not in non-diabetic patients. Cut-off values were determined from non-diabetics as 3.56 ng/mL for bioavailable vitamin D and 26.56 mg/dL for remnant cholesterol. Logistic regression analysis in the control group showed that the odds ratio for increasing remnant cholesterol above the cut-off value was determined as 2.01 for low bioavailable vitamin D and 1.1 for elevated CRP. However, in T2DM there was no significant relationship. In all subjects, low bioavailable vitamin D increased the remnant cholesterol above the cut-off by 2.18-fold independent of the presence of T2DM. However, there was no significant risk to increase remnant cholesterol, considering a total 25(OH) D deficiency in all groups. Conclusions Low bioavailable vitamin D was found to be a risk factor for elevated remnant cholesterol. This relationship was not detected in patients with T2DM. We believe that the inflammation observed in Diabetes Mellitus may increase the concentrations of VDBP and a decrease in bioavailable vitamin D levels. Therefore, measuring VDBP and calculating the bioavailable vitamin D may provide additional information about the actual vitamin D status.

Magnetic resonance spectroscopy to assess hepatic steatosis in patients with lipodystrophy.

BACKGROUND/AIMS: Lipodystrophy is a rare metabolic disorder characterized by near total or partial lack of subcutaneous adipose tissue and associated with insulin resistance. We aimed to evaluate the efficacy of magnetic resonance spectroscopy imaging (MRS) to explore the fat content of the liver in patients with lipodystrophy and to determine the relationship between the liver fat accumulation and clinical presentations of lipodystrophy. MATERIALS AND METHODS: Between July 2014 and February 2016, 34 patients with lipodystrophy were assessed by MRS for quantification of hepatic steatosis. All patients had metabolic abnormalities associated with insulin resistance. Metabolic parameters and the MRS findings were analyzed to identify potential correlations between the liver fat content and disease severity. RESULTS: The MRS fat ratios (MRS-FR) were markedly higher, indicating severe hepatic steatosis in lipodystrophy. Patients with generalized and partial lipodystrophy had comparable levels of MRS-FRs, although patients with generalized lipodystrophy were significantly younger. Patients with genetically based lipodystrophy had elevated MRS-FR compared to those with acquired lipodystrophy (p=0.042). The MRS-FR was positively correlated with liver enzyme alanine aminotransferase (p=0.028) and serum adiponectin (p=0.043). CONCLUSION: Our data suggest that MRS might be an effective, noninvasive imaging method to quantify hepatic fat content in patients with lipodystrophy. Further studies are needed to validate the technique and threshold values which would allow accurate comparison of data acquired by different machines and centers.

Preliminary study of serum Galectin-1 in breast cancer carcinogenesis [Izmir Oncology Group (IZOG) study].

PURPOSE: Galectin-1 is a lectin involved in the carcinogenesis of many cancers. In the present study, we aimed to investigate the importance of galectin-1 in breast cancer carcinogenesis and its relationship with tumor development. METHODS: Patients who were diagnosed with new breast cancer and a healthy volunteer population were included in the study. Preoperative and postoperative (1 month following visit at the medical oncology outpatient clinic) serum samples were collected from breast cancer patients and the healthy volunteer control group. RESULTS: There was no statistically significant difference between patients' age, height, weight and body mass index (BMI) (p>0.05). The mean galectin-1 value of the preoperative group was 2.16±0.69 ng/ml, in the postoperative group; 1.75±0.31 ng/ml, and the healthy control group 1.64±0.40 ng/ml. A comparison of mean galectin-1 values between the groups showed that the highest galectin-1 level was found in the preoperative patients. When the mean serum galectin-1 levels of preoperative and postoperative patients were compared, a statistically significant difference was found between the two groups (p<0.001). Furthermore, a comparison of the control group and preoperative patients also revealed a statistically significant difference between the groups (p<0.001). When the control group and postoperative patients were compared, no statistically significant difference was found between them (p=0.16). CONCLUSION: Serum galectin-1 levels were higher in breast cancer patients than in the healthy control group. In addition, postoperative galectin-1 levels of breast cancer patients tended to decrease. This suggests that serum galectin-1 levels are important in breast carcinogenesis and positively correlated with the presence of tumors.

Determining residual adipose tissue characteristics with MRI in patients with various subtypes of lipodystrophy.

PURPOSE: We aimed to investigate residual adipose tissue with whole-body magnetic resonance imaging to differentiate between subtypes of lipodystrophy. METHODS: A total of 32 patients (12 with congenital generalized lipodystrophy [CGL], 1 with acquired generalized lipodystrophy [AGL], 12 with familial partial lipodystrophy [FPLD], and 7 with acquired partial lipodystrophy [APL]) were included. RESULTS: Despite generalized loss of metabolically active adipose tissue, patients with CGL1 caused by AGPAT2 mutations had a significant amount of residual adipose tissue in the scalp, earlobes, retro-orbital region, and palms and soles. No residual adipose tissue was noted particularly in the head and neck, palms and soles in CGL2 caused by BSCL2 mutations. CGL4 caused by mutations in the PTRF gene was characterized with well-preserved retro-orbital and bone marrow fat in the absence of any visible residual adipose tissue in other areas. No residual adipose tissue was observed in AGL. Despite loss of subcutaneous fat, periarticular adipose tissue was preserved in the lower limbs of patients with FPLD. Retro-orbital adipose tissue was surprisingly preserved in APL, although they lacked head and neck fat. CONCLUSION: Lipodystrophies are a heterogeneous group of disorders characterized by generalized or partial loss of adipose tissue, which can be congenital or acquired. Our results suggest that residual adipose tissue characteristics can help distinguish different subtypes of lipodystrophy.

Clinical spectra of neuromuscular manifestations in patients with lipodystrophy: A multicenter study.

Lipodystrophy is a heterogeneous group of disorders characterized by loss of adipose tissue. Here, we report on clinical spectra of neuromuscular manifestations of Turkish patients with lipodystrophy. Seventy-four patients with lipodystrophy and 20 healthy controls were included. Peripheral sensorimotor neuropathy was a common finding (67.4%) in lipodystrophic patients with diabetes. Neuropathic foot ulcers were observed in 4 patients. Drop foot developed in 1 patient with congenital generalized lipodystrophy type 1. Muscle symptoms and hypertrophy were consistent findings in congenital generalized lipodystrophy (21/21) and familial partial lipodystrophy (25/34); on the other hand, overt myopathy with elevated creatine kinase activity was a distinctive characteristic of congenital generalized lipodystrophy type 4. Muscle biopsies revealed myopathic changes at different levels. Accumulation of triglycerides was observed which contributes to insulin resistance. All patients with congenital generalized lipodystrophy suffered from tight Achilles tendons at various levels. Scoliosis was observed in congenital generalized lipodystrophy type 4 (2/2) and familial partial lipodystrophy type 2 (2/17). Atlantoaxial instability was unique to congenital generalized lipodystrophy type 4 (2/2). Bone cysts were detected in congenital generalized lipodystrophy type 1 (7/10) and congenital generalized lipodystrophy type 2 (2/8). Our study suggests that lipodystrophies are associated with a wide spectrum of neuromuscular abnormalities.

Clinical presentations, metabolic abnormalities and end-organ complications in patients with familial partial lipodystrophy.

OBJECTIVE: Familial partial lipodystrophy (FPLD) is a rare genetic disorder characterized by partial lack of subcutaneous fat. METHODS: This multicenter prospective observational study included data from 56 subjects with FPLD (18 independent Turkish families). Thirty healthy controls were enrolled for comparison. RESULTS: Pathogenic variants of the LMNA gene were determined in nine families. Of those, typical exon 8 codon 482 pathogenic variants were identified in four families. Analysis of the LMNA gene also revealed exon 1 codon 47, exon 5 codon 306, exon 6 codon 349, exon 9 codon 528, and exon 11 codon 582 pathogenic variants. Analysis of the PPARG gene revealed exon 3 p.Y151C pathogenic variant in two families and exon 7 p.H477L pathogenic variant in one family. A non-pathogenic exon 5 p.R215Q variant of the LMNB2 gene was detected in another family. Five other families harbored no mutation in any of the genes sequenced. MRI studies showed slightly different fat distribution patterns among subjects with different point mutations, though it was strikingly different in subjects with LMNA p.R349W pathogenic variant. Subjects with pathogenic variants of the PPARG gene were associated with less prominent fat loss and relatively higher levels of leptin compared to those with pathogenic variants in the LMNA gene. Various metabolic abnormalities associated with insulin resistance were detected in all subjects. End-organ complications were observed. CONCLUSION: We have identified various pathogenic variants scattered throughout the LMNA and PPARG genes in Turkish patients with FPLD. Phenotypic heterogeneity is remarkable in patients with LMNA pathogenic variants related to the site of missense mutations. FPLD, caused by pathogenic variants either in LMNA or PPARG is associated with metabolic abnormalities associated with insulin resistance that lead to increased morbidity.

Interference in ACTH immunoassay negatively impacts the management of subclinical hypercortisolism.

PURPOSE: Low plasma corticotropin is considered a useful parameter for the diagnosis of subclinical hypercortisolism in patients with an adrenal incidentaloma. However, immunoassays are vulnerable to interference from endogenous antibodies. In this study, subjects who underwent Hypothalamus-pituitary-adrenal axis evaluation for the assessment of subclinical hypercortisolism were evaluated. The objective of the study was to ascertain whether antibody interference in corticotropin immunoassay affected the diagnostic work-up and clinical decisions. METHODS: The 437 consecutive patients with incidentally discovered adrenal adenomas were included in this single centre study. Patients who had a combination of a nonsuppressed corticotropin concentration (>4.4 pmol/L) and a non-suppressed cortisol concentration after 1 mg overnight dexamethasone suppression test (>50 nmol/L) were selected. Eight eligible subjects without specific features of Cushing's syndrome were identified and recruited for interference studies and follow-up. Nine controls including one patient with unilateral adrenalectomy and one patient with Cushing's disease were recruited as well. MEASUREMENTS: Eligible subjects and controls were subjected to hormonal tests and investigations for suspected interference. Interference studies included measurement of corticotropin on a different analytical platform, serial dilutions, polyethylene glycol precipitation and heterophilic antibody analysis. Patients were followed with clinical and laboratory parameters for a median duration of 30 (12-90) months. RESULTS: Antibody interference was identified in four patients. Rheumatoid factor was responsible for the interference in one patient. Clinical management of the patients was affected by the erroneous results. Interference tests were negative in control subjects. CONCLUSIONS: Erroneous results associated with analytical interference negatively impacted on clinical decision making in this patient group. This should be considered particularly in conditions such as subclinical hypercortisolism which decisions depend on laboratory investigations mainly. Analytical interference could explain the high variability observed both in field measurements from patients who were expected to have lower corticotropin concentrations and in subclinical hypercortisolism prevalence reported by different studies. Many problems can be resolved by ensuring good communication between clinical and laboratory staff.

The alterations of serum FGF-21 levels, metabolic and body composition in early breast cancer patients receiving adjuvant endocrine therapy.

BACKGROUND: In early breast cancer patients, the effects of hormonal therapy (tamoxifen and aromatase inhibitors) on plasma fibroblast growth factor 21 (FGF-21), lipid levels and body composition have not yet been investigated. Therefore, we aimed to analyze the relationship between FGF-21 and body composition as well as the effects of tamoxifen and aromatase inhibitors on plasma lipid levels, FGF-21, and body composition. METHODS: A total of 72 patients were treated with either tamoxifen or aromatase inhibitors due to their menopausal status after adjuvant radiotherapy. Each patient was followed-up over a period of 1 year. Changes in body composition and serum lipid profile, glucose and FGF-21 levels were evaluated. We recorded the type of hormonal therapy, body mass index, waist-to-hip ratio, lipid profile, and FGF-21 levels both at the beginning and after 12 months. RESULTS: There was a statistically significant decrease in serum FGF-21 levels after 12 months of adjuvant endocrine therapy (46 ± 19.21 pg/ml vs. 30.99 ± 13.81 pg/ml, p< 0.001). Total body water (p< 0.001), serum glucose (p= 0.036) and triglyceride levels (p< 0.001) also exhibited a significant decrease. The decreases in total cholesterol and low-density lipoprotein were not statistically significant. Likewise, high-density lipoprotein increased after adjuvant endocrine therapy, although it did not reach statistical significance. The changes in body composition, glucose, lipid profile and FGF-21 were similar in tamoxifen and aromatase inhibitor groups. A positive correlation was found between basal weight, fat mass, fat-free mass and serum FGF-21 levels; however, the correlation was maintained only for the fat-free mass at the 12th month. CONCLUSION: As part of the present study, we suggest that both tamoxifen and aromatase inhibitors can reduce FGF-21 levels independently of body compositions, and these drugs can provide antihyperlipidemic, antidiabetic and cardio-protective effects. We also recommend that serum FGF-21 level can be utilized as a tumor biomarker in early-stage breast cancer and for monitoring purposes. FGF-21 levels may help physicians estimate prognosis, too. Further studies with larger populations may shed light on the role of FGF-21 in breast cancer.

Natural History of Congenital Generalized Lipodystrophy: A Nationwide Study From Turkey.

CONTEXT: Congenital generalized lipodystrophy (CGL) is a rare autosomal recessive disorder characterized by near-total lack of body fat. OBJECTIVE: We aimed to study natural history and disease burden of various subtypes of CGL. DESIGN: We attempted to ascertain nearly all patients with CGL in Turkey. SETTING: This was a nationwide study. PATIENTS OR OTHER PARTICIPANTS: Participants included 33 patients (22 families) with CGL and 30 healthy controls. MAIN OUTCOME MEASURE(S): We wanted to ascertain genotypes by sequencing of the known genes. Whole-body magnetic resonance imaging was used to investigate the extent of fat loss. Metabolic abnormalities and end-organ complications were measured on prospective follow-up. RESULTS: Analysis of the AGPAT2 gene revealed four previously reported and four novel mutations (CGL1; c.144C>A, c.667_705delinsCTGCG, c.268delC, and c.316+1G>T). Analysis of the BSCL2 gene revealed four different homozygous and one compound heterozygous possible disease-causing mutations (CGL2), including four novel mutations (c.280C>T, c.631delG, c.62A>T, and c.465-468delGACT). Two homozygous PTRF mutations (c.481-482insGTGA and c.259C>T) were identified (CGL4). Patients with CGL1 had preservation of adipose tissue in the palms, soles, scalp, and orbital region, and had relatively lower serum adiponectin levels as compared to CGL2 patients. CGL4 patients had myopathy and other distinct clinical features. All patients developed various metabolic abnormalities associated with insulin resistance. Hepatic involvement was more severe in CGL2. End-organ complications were observed at young ages. Two patients died at age 62 years from cardiovascular events. CONCLUSIONS: CGL patients from Turkey had both previously reported and novel mutations of the AGPAT2, BSCL2, and PTRF genes. Our study highlights the early onset of severe metabolic abnormalities and increased risk of end-organ complications in patients with CGL.

Partial lipodystrophy of the limbs in a diabetes clinic setting.

OBJECTIVE: Partial lipodystrophy of the limbs (PLL) is a newly described form of lipodystrophy that is characterized by symmetrical distal lipoatrophy of the limbs and insulin resistant diabetes. RESEARCH DESIGN AND METHODS: In this study, we prospectively screened our patients with type 2 diabetes for the presence of PLL phenotype. Metabolic parameters of PLL patients were compared to those with type 2 diabetes who applied to our diabetes clinic during the same period of time. RESULTS: Between Sep 2013 and Mar 2015, 2020 patients with type 2 diabetes were evaluated for the presence of PLL. PLL was confirmed in 16 patients. The prevalence of PLL was calculated as 0.79% in our diabetes clinic. The most common phenotypic presentations were loss of subcutaneous fat in the forearms, calves and thighs, and loss of fat in forearms and calves. Patients with PLL had poor metabolic control and marked insulin resistance compared to subjects with type 2 diabetes. Diabetes had been diagnosed at a younger age in patients with PLL. Patients with PLL also had more atherogenic lipid profiles. CONCLUSIONS: Our data suggests that PLL is a relatively common form of lipodystrophy in diabetes clinics, which is associated with poor metabolic control and marked insulin resistance. The recognition of PLL in patients with type 2 diabetes can help better clinical management by alerting the physician to these associated co-morbidities.

Serum apelin levels and body composition changes in breast cancer patients treated with an aromatase inhibitor.

PURPOSE: The adipose tissue plays a role in carcinogenesis with the adipokines it generates. Apelin is an anti-obesigenic adipokine, and assumes roles in both vascularization and tumor cell proliferation. The present study aimed to investigate changes in apelin levels, in postmenopausal breast cancer (BC) patients receiving aromatase inhibitors (AIs). METHODS: Forty early-stage postmenopausal BC patients treated with AIs with no history of chemotherapy administration were included in the study. At the beginning, we measured serum apelin levels in postmenopausal BC patients who were receiving AIs and healthy women of similar age and normal body mass index (BMI) (control group). We evaluated changes in the body composition, serum lipid profile and serum apelin levels at the beginning and the 12th month through anthropometric measurements and bioelectric impedance analysis. RESULTS: Forty subjects with postmenopausal BC had a median age of 57 years (range 44-82)). BC patients exhibited significantly higher apelin levels and body mass index (BMI) scores compared to the control group (p=0.0001, p=0.0001, respectively). The 12th month's measurements indicated reduced apelin levels in 24 patients (60%) and increased apelin levels in 16 patients (40%) compared to the initial figures. With respect to the parameters, the patients with reduced apelin levels had significantly different waist-to-hip ratio (WHR) and fat mass scores compared to those with higher apelin levels (p=0.008, p=0.047, respectively). CONCLUSION: This study showed that postmenopausal BC patients had high levels of apelin and high BMI scores. This finding suggests that apelin promoted carcinogenesis particularly in obese individuals. The massive and metabolic changes observed in the fat tissues of the postmenopausal BC patients receiving AIs will especially affect the BC-associated outcome.

The Effects of Adjuvant Endocrine Treatment on Serum Leptin, Serum Adiponectin and Body Composition in Patients with Breast Cancer: The Izmir Oncology Group (IZOG) Study.

BACKGROUND: A limited number of studies have been conducted on the effects of hormonal therapy with tamoxifen (TMX) or aromatase inhibitors (AIs) on plasma levels of leptin and adiponectin, as well as body composition in breast cancer (BC) patients. Therefore, we aimed to analyze the relationship between adipocytokines and body composition as well as the effects of TMX and AIs on plasma adiponectin, leptin, leptin/adiponectin ratio (LAR) and body composition. METHODS: Patients were treated with either TMX or AI according to their menopausal status after adjuvant radiotherapy. Changes in body composition and serum leptin and adiponectin levels were evaluated. We recorded the type of hormonal therapy, BMI, waist/hip ratio (WHR), leptin and adiponectin levels at study entry, and after 6 and 12 months. RESULTS: From baseline to the 6- and 12-month follow-ups, there were statistically significant increases in WHR (p = 0.003), fat mass (p = 0.041), and serum leptin (p < 0.001) and adiponectin levels (p < 0.001). The changes in body composition and serum leptin and adiponectin levels were similar in TMX and AI groups. A statistically significant decrease was found in total body water and LAR (p < 0.001). Although weight and body fat percentage increased, such increases were not statistically significant. A positive correlation was found between baseline BMI and serum leptin levels. This correlation was maintained at 6 and 12 months. The negative correlation found between serum adiponectin levels at baseline and baseline BMI did not last throughout the study. CONCLUSION: In this study, increased leptin and adiponectin levels and a decreased LAR were found in both AI and TMX groups. These changes might have occurred through both mechanisms of hormonal therapy and body composition changes. Therefore, AIs and TMX may exert their protective effects for BC patients by decreasing LAR rather than affecting leptin or adiponectin alone.

Acquired partial lipodystrophy is associated with increased risk for developing metabolic abnormalities.

OBJECTIVE: Acquired partial lipodystrophy (APL) is a rare disorder characterized by progressive selective fat loss. In previous studies, metabolic abnormalities were reported to be relatively rare in APL, whilst they were quite common in other types of lipodystrophy syndromes. METHODS: In this nationwide cohort study, we evaluated 21 Turkish patients with APL who were enrolled in a prospective follow-up protocol. Subjects were investigated for metabolic abnormalities. Fat distribution was assessed by whole body MRI. Hepatic steatosis was evaluated by ultrasound, MRI and MR spectroscopy. Patients with diabetes underwent a mix meal stimulated C-peptide/insulin test to investigate pancreatic beta cell functions. Leptin and adiponectin levels were measured. RESULTS: Fifteen individuals (71.4%) had at least one metabolic abnormality. Six patients (28.6%) had diabetes, 12 (57.1%) hypertrigylceridemia, 10 (47.6%) low HDL cholesterol, and 11 (52.4%) hepatic steatosis. Steatohepatitis was further confirmed in 2 patients with liver biopsy. Anti-GAD was negative in all APL patients with diabetes. APL patients with diabetes had lower leptin and adiponectin levels compared to patients with type 2 diabetes and healthy controls. However, contrary to what we observed in patients with congenital generalized lipodystrophy (CGL), we did not detect consistently very low leptin levels in APL patients. The mix meal test suggested that APL patients with diabetes had a significant amount of functional pancreatic beta cells, and their diabetes was apparently associated with insulin resistance. CONCLUSIONS: Our results show that APL is associated with increased risk for developing metabolic abnormalities. We suggest that close long-term follow-up is required to identify and manage metabolic abnormalities in APL.

The investigation of cytogenetic and oxidative effects of diffractaic acid on human lymphocyte cultures

Diffractaic acid (DA) is a naturally occurring depside derivative found in several lichen species. It has a wide range of important biological effects such as analgesic and antiviral properties, although its cytotoxic, cytogenetic and oxidative effects have not been investigated in human blood tissue yet. Therefore, increasing concentrations (1, 5, 10, 25, 50, 100 and 200 mgL-1) of DA was added into human whole blood cultures. 3-(4.5-dimethylthiazol-2-yl)-2.5-diphenyl tetrazolium bromide (MTT) assay was used to assess the cell viability and/or cytotoxicity and genotoxic damage potential of DA using chromosome aberration (CA) and micronucleus (MN) tests were performed. In addition, oxidative alterations were determined by the total antioxidant capacity (TAC) and total oxidant status (TOS) assays. The results revealed that DA reduced cell viability at higher concentrations than 50 mgL-1. The all tested concentrations of DA were non-genotoxic. In vitro treatments with DA led to increases of TAC levels in the cultured blood cells without changing the TOS levels as compared to the control group. Consequently, DA exhibited a significant non-mutagenic and antioxidant potential in vitro.

Clinical biochemistry laboratory rejection rates due to various types of preanalytical errors.

INTRODUCTION: Preanalytical errors, along the process from the beginning of test requests to the admissions of the specimens to the laboratory, cause the rejection of samples. The aim of this study was to better explain the reasons of rejected samples, regarding to their rates in certain test groups in our laboratory. MATERIALS AND METHODS: This preliminary study was designed on the rejected samples in one-year period, based on the rates and types of inappropriateness. Test requests and blood samples of clinical chemistry, immunoassay, hematology, glycated hemoglobin, coagulation and erythrocyte sedimentation rate test units were evaluated. Types of inappropriateness were evaluated as follows: improperly labelled samples, hemolysed, clotted specimen, insufficient volume of specimen and total request errors. RESULTS: A total of 5,183,582 test requests from 1,035,743 blood collection tubes were considered. The total rejection rate was 0.65 %. The rejection rate of coagulation group was significantly higher (2.28%) than the other test groups (P < 0.001) including insufficient volume of specimen error rate as 1.38%. Rejection rates of hemolysis, clotted specimen and insufficient volume of sample error were found to be 8%, 24% and 34%, respectively. Total request errors, particularly, for unintelligible requests were 32% of the total for inpatients. CONCLUSIONS: The errors were especially attributable to unintelligible requests of inappropriate test requests, improperly labelled samples for inpatients and blood drawing errors especially due to insufficient volume of specimens in a coagulation test group. Further studies should be performed after corrective and preventive actions to detect a possible decrease in rejecting samples.