The protective role of selenium against high-fructose corn syrup-induced kidney damage: a histopathological and molecular analysis.

With the growth of the food industry, fructose, the intake of which increases with food, causes obesity and metabolic syndrome. Kidney damage may develop from metabolic syndrome. Selenium (Se) participates in the structure of antioxidant enzymes and has a medicinal effect. In this work, the protective impact of Se on kidney damage produced by high-fructose corn syrup (HFCS) via endoplasmic reticulum (ER) stress was examined. The study comprised four groups, each consisting of ten experimental animals: control, HFCS (20%-HFCS), HFCS (20%-HFCS), + Se (0.3 mg/kg/day/po), and Se (0.3 mg/kg/day/po) alone. The duration of the experiment was 6 weeks. Kidney tissues were stained with hematoxylin and eosin for histological examination. Immunohistochemical analysis was conducted to assess TNF-α and caspase-3 levels. The spectrophotometric evaluation was performed to measure TOS (total oxidant status), TAS (total antioxidant status), and OSI (oxidative stress index) levels. The PERK, ATF4, CHOP, BCL-2, and caspase-9 gene expression levels were assessed by the RT-qPCR method. After Se treatment, histopathological abnormalities and TNF-α and caspase-3 levels in the HFCS+Se group decreased (p < 0.001). While TOS and OSI levels increased dramatically in the HFCS group, TAS values decreased significantly but improved after Se application (p < 0.001). The expression levels of the genes PERK, ATF4, CHOP, and caspase-9 were significantly lower in the HFCS group when compared to the HFCS+Se group (p < 0.05). Our findings suggest that Se may protect against ER stress, oxidative stress, apoptosis, and kidney damage caused by high-dose fructose consumption.

Involvement of TRPM7 Channel on the Induction of Diabetic Neuropathic Pain in Mice: Protective Role of Selenium and Curcumin.

Excessive levels of the mitochondrial reactive oxygen radical (mitSOX) and Ca2+ influx were found to cause neuropathic pain in patients with diabetes mellitus (DM). Naltriben (NLT) and mitSOX activate the transient receptor (TRP) melastatin 7 (TRPM7) channel, but antioxidants and carvacrol inhibit it. Selenium (Se) and curcumin (CRC) have been thoroughly studied for their modulator effects on streptozotocin (STZ)-induced neuropathic pain, apoptosis, and oxidative stress through the blockage of TRP channels in dorsal root ganglion (DRG) neurons. It has not yet been fully understood how Se and CRC protect against STZ-induced neuropathic pain by modulating TRPM7. Here, we assessed how Se and CRC affected the Ca2+ influx, mitSOX-mediated oxidative damage, and apoptosis in the DRGs of mice through modifying TRPM7 activity. Seven groups (control, Se, CRC, STZ, STZ + Se, STZ + CRC, and STZ + Se + CRC) were induced from the 56 male mice. We observed that the STZ-induced stimulation of TRPM7 increased mechanical neuropathic pain (von Frey), thermal neuropathic pain (hot plate), cytosolic Ca2+, TRPM7 current density, TRPM7 expression, lipid peroxidation, mitSOX, cytosolic ROS, apoptosis, caspase-3, caspase-8, and caspase-9 concentrations, whereas Se and CRC therapies diminished the alterations. The STZ-mediated decreases of DRG viability, brain glutathione, glutathione peroxidase, vitamin A, and vitamin E concentrations were also upregulated in the treatment groups by the therapies. These findings collectively imply that an imbalance of neuropathic pain, oxidative neurotoxicity, and apoptosis in the mice is caused by the STZ-mediated activation of TRPM7. However, the downregulation of TRPM7 activity caused by the injections of Se and CRC reduced the neurotoxicity and apoptosis.

Relationship between glycosylated hemoglobin and vitamin B12 deficiency anemia.

OBJECTIVE: Previous studies showed that vitamin B12 deficiency anemia causes a false increase in glycosylated hemoglobin (HbA1c) and that HbA1c decreases with B12 treatment. However, no study has been conducted on how much an increase in hemoglobin (Hgb) level causes a decrease in HbA1c level after treatment. METHODS: The study included 37 patients who were not diagnosed with diabetes, did not use anti-diabetic drugs, were pre-diabetic according to HbA1c level, and were diagnosed with vitamin B12 deficiency anemia in the patient group and 40 healthy volunteers of similar age and gender characteristics in the control group. The patient group was given 1 mg/day of cyanocobalamin (vitamin B12) orally for 3 months. Patients' Hgb, mean corpuscular volume, fasting plasma glucose, HbA1c, and vitamin B12 values were compared at the beginning and at the end of the 3rd month. RESULTS: In the patient group, it was determined that 0.94 mg/dL increase in Hgb after vitamin B12 treatment caused a 0.24 decrease in HbA1c (%). The initial HbA1c of the patient group was 6.01±0.20 and the 3rd-month HbA1c was 5.77±0.33; the initial and 3rd-month Hgb values were 11.31±0.28 and 12.26±0.33, respectively; the initial and 3rd-month vitamin B12 (ng/L) levels were 112.43±7.18 and 408.48±119.61, respectively; and there was a significant difference between the initial and 3rd-month values (p<0.001, p<0.001, p<0.001, respectively). Moreover, 35% of the patients in the patient group had no diagnosis of prediabetes according to the HbA1c level at the end of the 3rd month. CONCLUSION: Elimination of vitamin B12 deficiency anemia before making a diagnosis or treatment decision according to HbA1c level will prevent patients from misdiagnosis of diabetes and unnecessary treatment changes in diabetic patients.

Relationship between glycosylated hemoglobin and iron deficiency anemia: A common but overlooked problem.

INTRODUCTION: Both diabetes mellitus (DM) and iron deficiency anemia (IDA) are prevalent in every area of the world, and so, the possibility of these two diseases co-existing is also very high. It is our belief that clinical results of any correlation between iron status of the body and glycosylated haemoglobin (HbA1c) would be beneficial to many patients, therefore in this study, the effect of IDA on HbA1c was investigated. MATERIALS - METHODS: A total of 146 patients with DM and IDA were evaluated prospectively. While the patients were administered 270 mg/day of ferrous sulphate (80 mg elemental iron) orally for three months for the treatment of IDA, no interventions were made for the treatment of DM. Patient levels of hemoglobin (Hb), hematocrit, red blood cells (RBC), mean corpuscular volume (MCV), platelet, white blood cells (WBC), serum iron, serum iron binding capacity (SIBC), ferritin, fasting plasma glucose (FPG), HbA1c, body mass index (BMI), C-reactive protein (CRP) values were measured at baseline and at the third month of treatment with iron, and were compared. RESULTS: The median age of our patients was 45 (40-50) and median duration of diabetes was 3 years (1,75-5). While the baseline median Hb was 10.4 (mg/dL) (9.5-11.1), MCV was 74 (fL) (70.8-77), ferritin was 4 (ug/L) (3-6) at three months, Hb was measured at 12.6 (mg/dL) (12.1-13.2), MCV was measured at 82 (fL) (80-86), ferritin was measured at 15 (ug/L) (9-21.2) and was significantly higher compared to baseline values (p < 0.001). The baseline median HBA1c of patients was 7.09 ±â€¯0.51 (%) and three month HBA1c was 6.69 ±â€¯0.53 (%), which was significantly lower than when comparing baseline values with values at third month (p < 0.001). Baseline and three month values for FPG were 118 (mg/dL) (108-132) and 116 (mg/dL) (106-125) respectively, and there was no significant difference (p:0.07). A 2.2 mg/dL (1.5-3.5) increase in median Hb level accompanied a 0.4 % (0.2-0.6) decrease in median HbA1c levels (Spearman rho = -0.362; p < 0.001). CONCLUSION: Our study has shown conclusivly that IDA is related to increased HbA1c concentrations and HbA1c decreases significantly following treatment with iron. IDA should be considered before making any decisions regarding diagnosis or treatment according to HbA1c.

The Relationship between Third-generation TSH Receptor Antibody Positivity and Cumulative Methimazole Dose Used until Remission in Graves' Disease.

OBJECTIVE: To determine the relationship between the positivity of third-generation TSH receptor antibody (TRAb) at the time of diagnosis and the cumulative methimazole dose used until remission in patients with Graves' disease. STUDY DESIGN: Cross-sectional, descriptive study. PLACE AND DURATION OF STUDY: Department of Endocrinology and Metabolic Diseases, University of Health Sciences, Kartal Dr. Lütfi Kirdar City Hospital, Turkey from 2016 to 2018. METHODOLOGY: Newly diagnosed Graves' patients were included in the study. The patients were divided into two groups according to whether they entered remission (n: 21) or not (n: 20), in the 18th month of methimazole treatment. In addition, the patients were further divided into two categories, according to TRAb status at the time of diagnosis as negative (n: 17) or positive (n: 24). The TRAb positivity and the cumulative methimazole dose they used until the month of remission were compared in these groups. RESULTS: The mean time to reach remission in 41 patients was 20.5 ± 3.1 months. TSH receptor antibody positivity rate was 58.5%. When the TRAb positivity of the groups was compared according to the state of having remission in the 18th month of the treatment, the positivity rate in the non-remission group was statistically significantly higher (p = 0.023).The time to go into remission was longer and the cumulative methimazole dose requirement was higher in the TRAb positive group (p <0.001). CONCLUSION: Graves' disease patients with positive third-generation TRAb were found to have a lower rate of remission in the 18-month period compared to negative patients. Key Words: Graves' disease, TSH receptor antibody, Cumulative, Methimazole.

Outcomes of transition from premixed and intensive insulin therapies to insulin aspart/degludec co-formulation in type 2 diabetes mellitus: a real-world experience.

INTRODUCTION: To evaluate the efficacy and safety of transition from premixed and intensive insulin to twice-daily insulin degludec/aspart (IDegAsp) co-formulation in patients with type 2 diabetes mellitus. MATERIAL AND METHODS: In this 12-week study, patients receiving twice-daily premixed insulin therapy in group 1 (n = 55) were switched to twice-daily IDegAsp. In group 2 (n = 60), patients on intensive insulin therapy were switched to IDegAsp injected twice a day. Inter- and intragroup comparisons were made. RESULTS: A total of 115 patients were included in the study. There was a significant improvement in glycaemic control, median daily total insulin dose, body mass, body mass index, and hypoglycaemic events in group 1 and group 2 with the switch to IDegAsp (p < 0.05). The decrease in median daily total insulin dose requirement in group 2 was higher than that of group 1 (p = 0.001). There was no difference between groups in terms of other parameters (p > 0.05). CONCLUSIONS: The current analysis indicates that IDegAsp treatment improves outcomes, with the most notable differences observed in daily total insulin requirement, body mass, and hypoglycaemia.

The effect of low and high dose empagliflozin on HbA1c and lipid profile in type 2 diabetes mellitus: A real-world data.

OBJECTIVE: This study aims to evaluate the efficacy and safety of the addition of 10 or 25 mg of empagliflozin to patients with type 2 diabetes mellitus using a maximum tolerable dose of metformin and gliclazide. METHODS: A total of 60 patients who had been receiving a maximum tolerable dose of metformin plus gliclazide. was divided into two groups in this study. In the first group (Group 1, n=32), 10 mg empagliflozin was added to the current treatment once a day, and in the second group (Group 2, n=28) 25 mg empagliflozin was added to the same treatment once a day. Biochemical results, weight and blood pressure changes of the patients in both groups were evaluated before and after 12 weeks of empagliflozin addition. Patients who developed urinary tract and genital infections after treatment were recorded. RESULTS: There was a statistically significant decrease in HbA1c in both groups after empagliflozin treatment (Group 1, p<0.001 and Group2, p=0.001). When the lipid profile was evaluated, no significant difference was found between basal and post-treatment parameters (p>0.05). Patients in Group 1 and Group 2 lost 2.6±1.2 and 3.8±2.0 kg of body weight, respectively (p<0.0001 for each). There were also significant reductions in systolic and diastolic blood pressure for groups 1 and 2 (p<0.0001 for each). Although there was a numerical increase in the urinary tract and genital infections in both groups after empagliflozin treatment, there was no statistically significant difference compared to the pre-treatment period (p>0.05). CONCLUSION: Two doses of empagliflozin added to the present treatments showed a dose-independent improvement in glycemic control and a neutral effect on lipid metabolism.

The combination of acute pancreatitis and toxic hepatitis developing secondary to exposure to malathion : a case report.

Organophosphate(OPH) compounds are cholinesteraseinhibiting chemicals used as pesticide. Pancreatitis secondary to malathion toxicity is rare and toxic hepatitis has been reported in only one case. In this paper, we report the case of the combination of acute pancreatitis and toxic hepatitis, which developed in a 30-year old farm worker and the mechanism is discussed in this first report of its kind. Awareness of this complication should prompt earlier investigation because early diagnosis coupled with timely therapeutic measures may improve patient prognosis.

The impact of gallic acid on the methotrexate-induced kidney damage in rats.

Prolonged use of an antineoplastic agent methotrexate (MTX), can cause numerous side effects such as nephrotoxicity. The aim of this study was to examine the effects of MTX on kidneys and demonstrate the protective effects of gallic acid (GA). Twenty-four, male, rats distributed into three groups. Each groups consisted eight rats and only saline was administered to the control group. The MTX group received a single dose (20 mg/kg) MTX intraperitoneally. The MTX + GA group received same dose MTX and 100 mg/kg GA orally during the 7 days. Renal functions, oxidative stress markers, histopathological and immunohistochemical changes were evaluated at the end of the experiment. Blood urea nitrogen, creatinine, uric acid levels and tissue oxidative stress markers, total oxidant status and oxidative stress index levels significantly increased and total antioxidant status levels significantly decreased in MTX group compared with the control group. At the histopathological examination hemorrhages, tubular cell necrosis, glomerulosclerosis, inflammatory cell infiltrations and proteinous materials in tubules were noticed in MTX group. Immunohistochemical examination revealed that increased expressions of serum amyloid A (SAA), tumor necrosis factor alpha (TNF-α), prostaglandin E2 (PGE-2) and C-reactive protein (CRP) in tubular epithelial cells of kidneys in this group. There were no immunoreaction with SAA and CRP, only small number of PGE-2 and TNF-α positive tubular epithelial cells were observed in MTX + GA group. In conclusion, all evidence suggested that oxidative stress caused MTX-induced nephrotoxicity and GA prevent the kidney from the nephrotoxicity due to its antioxidant and anti-inflammatory activities.

Investigation of pulmonary involvement in inflammatory bowel disease in an experimental model of colitis.

BACKGROUND/AIMS: Inflammatory bowel disease (IBD) may also involve various extra-intestinal organs. Clinical studies have found asymptomatic/symptomatic pulmonary involvement in 1% to 6% of patients with IBD. The present study histopathologically investigated pulmonary involvement in an experimental model of colitis in order to demonstrate pulmonary tissue involvement in IBD and to expose potential etiological factors. It also explored the relation between inflammation and tissue concentrations of vascular endothelial growth factor (VEGF) and tumor necrosis factor α (TNF-α). METHODS: The study comprised 24 male Wistar albino rats. The rats were divided into four groups of six rats each. Acute colitis was induced in two separate groups using either the dextran sulphate sodium (DSS) or trinitrobenzene sulfonic acid (TNBS) method, while the other two groups were used as controls for each model of colitis. Wallace scoring was used for macroscopic assessment of colitis, and the lungs were histopathologically examined. Concentrations of VEGF and TNF-α in pulmonary tissue were measured by the enzyme-linked immunosorbent assay method. RESULTS: The number of animals that had alveolar hemorrhage was significantly higher in the TNBS-induced colitis and DSS-induced colitis groups compared to their own control groups (p = 0.015 and p = 0.015, respectively). VEGF and TNF-α concentrations in pulmonary tissues were significantly increased in both the TNBS colitis and DSS colitis groups compared to their own control groups (p = 0.002 and p = 0.004, respectively; and p = 0.002 and p = 0.002, respectively). CONCLUSIONS: The present study demonstrated that significant and serious histopathological changes directly associated with colitis occur in the lungs in IBD.

Amyloid Goiter Secondary to Ulcerative Colitis.

Diffuse amyloid goiter (AG) is an entity characterized by the deposition of amyloid in the thyroid gland. AG may be associated with either primary or secondary amyloidosis. Secondary amyloidosis is rarely caused by inflammatory bowel diseases. Secondary amyloidosis is relatively more common in the patients with Crohn's disease, whereas it is highly rare in patients with ulcerative colitis. Diffuse amyloid goiter caused by ulcerative colitis is also a rare condition. In the presence of amyloid in the thyroid gland, medullary thyroid cancer should be kept in mind in the differential diagnosis. Imaging techniques and biochemical tests are not very helpful in the diagnosis of secondary amyloid goiter and the definitive diagnosis is established based on the histopathologic analysis and histochemical staining techniques. In this report, we present a 35-year-old male patient with diffuse amyloid goiter caused by secondary amyloidosis associated with ulcerative colitis.

Insulinoma-Induced Hypoglycemia in a Patient with Insulinoma after Gastrojejunostomy for Prepyloric Ulcer.

Hyperinsulinism due to dumping syndrome following gastric surgery is an uncommon condition. It is specified with hypoglycemic attacks. However, linking symptoms to dumping syndrome in each patient to whom gastric surgery was performed leads to inappropriate diagnosis and therapy. Insulinoma and other causes that give rise to hyperinsulinemia should not be ignored and these diagnoses should be excluded. In this paper, 71-year-old male patient who was followed up for 2 years with a false conclusion of dumping syndrome and operated on due to insulinoma diagnosed at endoscopic ultrasonography is presented in the light of the literature.

Propylthiouracil-induced alveolar hemorrhage.

Thionamide induced vasculitis is a multisystem disease. The patients may present with different clinical signs and findings due to organ involvement. These patients are almost always perinuclear antineutrophil cytoplasmic antibody (pANCA) or antimyeloperoxidase (MPO) positive. Clinical findings are not seen in all of the patients who are ANCA positive while using thionamide. Although symptoms usually resolve with drug discontinuation, some patients, however, require high-dose steroids, immunosuppressants, or plasmapheresis. We present here a case of alveolar hemorrhage induced by propilthiouracil (PTU) during treatment with PTU for Graves' disease; patients completely recovered with corticosteroid, cyclophosphamide, and plasmapheresis.

The role of carnitine in preventing renal damage developed as a result of infrarenal aortic ischemia-reperfusion.

BACKGROUND: This study was designed to use carnitine for preventing deposition of end products of lipid peroxidation in rat models in the prevention of ischemia-reperfusion (IR) damage frequently seen following operations of infrarenal abdominal aorta (AA). METHODS: Forty male rats of Sprague-Dawley type were evenly (n = 8) randomized to five groups: sham laparotomy (SHAM), carnitine control (CC), aortic IR (AIR), AIR + low-dose carnitine (AIR+LDC), and AIR + high-dose carnitine (AIR+HDC). RESULTS: Compared to other groups, serum creatinine levels of AIR group were significantly higher. Also tissue malondialdehyde (MDA) levels of AIR group were significantly higher compared to SHAM, CC, and AIR+HDC groups. In histopathological examination, although tubular necrosis atrophy and tubular degeneration observed in AIR group showed regression with low-dose carnitine, tubular necrosis atrophy, tubular degeneration, glomerular damage, and vascular congestion thrombosis decreased with high-dose carnitine. Total score of histological damage was significantly higher in AIR, AIR+LDC, and AIR+HDC groups compared to SHAM and CC groups. Moreover, total score of histological damage was significantly lower in AIR+HDC group than AIR+LDC group. CONCLUSIONS: In this study, we showed carnitine can partially prevent renal damage in infrarenal AIR models of rats. This result may open new prospects to us in the prevention of renal IR damage during surgery of aorta.

Plasmapheresis and corticosteroid treatment for persistent jaundice after successful drainage of common bile duct stones by endoscopic retrograde cholangiography.

Prolonged cholestasis is a very rare complication of endoscopic retrograde cholangiography (ERC). Only few cases with this complication are reported in the English literature. We report persisting cholestatic jaundice in a 73-year old man after successful therapeutic ERC for choledocholithiasis. Serologic tests for viral and autoimmune hepatitis were all negative. A second-look ERC was normal also. He denied any medication except for prophylaxis given intravenous 1 g ceftriaxone prior to the ERC procedure. After an unsuccessful trial with ursodeoxycholic acid and cholestyramine for 2 wk, this case was efficiently treated with corticosteroids and plasmapheresis. His cholestatic enzymes became normal and intense pruritus quickly resolved after this treatment which lasted during his follow-up period. We discussed the possible mechanisms and treatment alternatives of intrahepatic cholestasis associated with the ERC procedure.