Habib Bilen

Tissue damage and oxidant/antioxidant balance.

The oxidant/antioxidant balance in healthy tissues is maintained with a predominance of antioxidants. Various factors that can lead to tissue damage disrupt the oxidant/antioxidant balance in favor of oxidants. In this study, disruptions of the oxidant/antioxidant balance in favor of oxidants were found to be a consequence of the over-consumption of antioxidants. For this reason, antioxidants are considered to be of importance in the prevention and treatment of various types of tissue damage that are aggravated by stress.

Conjunctival Flora in Patients With Type 1 or Type 2 Diabetes Mellitus

Patients with diabetes mellitus (DM) are prone to infection because glucose in the skin, urine, mucous membranes, and tears promotes growth of microorganisms. Conjunctival flora develops soon after birth, and some saprophytic conjunctival flora play a pathogenic role when immune function is compromised, which can lead to serious infection. DM is one condition that may compromise immune status. In lacrimal function tests of DM patients, a decrease in breakup time (BUT) of lacrimal film and a decrease in Schirmer’s test results were seen. In the present study, conjunctival flora in patients with DM was compared with that in controls with regard to type and duration of diabetes and results of lacrimal function tests. Seventeen patients with type 1 DM (n=34 eyes), 66 patients with type 2 DM (n=132 eyes), and 50 control subjects (n=100 eyes) were included. The control group consisted of age-matched patients with no ophthalmologic problems other than refractive error. Clycosylated hemoglobin values were measured with highpressure liquid chromatography with the Hi-AUTOA1c analyzer (Kyoto Daiichi Kagatu Co., Ltd., Kyoto, Japan). Type and duration of diabetes and demographic data were recorded, and routine ophthalmologic examinations were performed; the BUT of lacrimal film was determined, and the results of Schirmer’s test were assessed. Microbiologic sampling was performed twice for both eyes with sterile cotton swabs. One sample was incubated in 2 mL of brain-heart infusion broth agar; the other was incubated for the presence of fungi in Sabouraud dextrose agar. Colony morphology, hemolysis, and Cram’s stain, as well as catalase, oxidase, and coagulase tests were performed. No growth was observed in 12 of 1 7 patients (35.4%) with type 1 DM, 28 of 66 patients (21.2%) with type 2 DM, and 25 of 50 control subjects (50%).Staphylococcus epidermidis (11.79%) andStaphylococcus aureus (11.7%) were the most frequently isolated organisms in the type 1 DM group, and Sepidermidis (24.2%) and Saureus (21.2%) were the predominant organisms in the type 2 DM group. In control subjects, Sepidermidis (22%), Saureus (12%), andCorynebacterium spp (10%) were the most frequently isolated organisms, and the number of eyes with growth of Saureus was significantly higher in the type 2 DM group than in the other groups (P<.01). Patients with diabetes are more prone to postoperative endophthalmitis than are nondiabetics, and preoperative application of antiseptic or antimicrobial agents to the conjunctiva may not sterilize the area. Impaired integrity of the posterior capsule may also increase the risk of endophthalmitis. Postoperative endophthalmitis is usually associated with gram-positive organisms (75%–80%); gram-negative organisms (15%–29%) and fungi (3%–13%) account for a smaller number of cases. A high rate of resistance to penicillin, ampicillin, and tetracycline was observed in Saureus isolates, although resistance to vancomycin was absent, rendering this molecule the most effective therapeutic option. In this study, Sepidermidis and Saureus were the 2 most frequently isolated organisms in patients with DM. It is concluded that the conjunctival flora in diabetic subjects differs from that in nondiabetic subjects. This should be considered preoperatively and postoperatively, and prophylactic and postoperative treatment should be administered accordingly to diabetic patients.

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.

Primary hyperparathyroidism presenting as a palatal and mandibular brown tumor.

Primary hyperparathyroidism is a fairly frequent pathologic diagnosis characterized by hypersecretion of parathyroid hormone, which results from adenomas in 80% to 85% of all cases. At clinical onset, the most common symptoms are hypercalcemia-related and some of them are pain due to kidney stones, polyuria, gastrointestinal, and neurologic disorders, whereas rarer symptoms are due to brown tumors and expansive lesions often found in fibrocystic osteitis. Brown tumors represent the terminal stage of the remodeling processes caused by an increased osteoclastic activity and fibroblastic proliferation during primary or secondary, albeit more seldom, hyperparathyroidism. The manifestation of primary hyperparathyroidism as skeletal disease has nearly disappeared in the last 2 decades. Cases are now most often diagnosed by the coincidental finding of asymptomatic hypercalcemia. Advanced screening techniques have made clinical evidence of bone disease rare. This article contains a case of brown tumor on the maxilla, palate, and mandible in addition to nephrectomy and proximal femur fracture, which are probably associated with primary hyperparathyroidism although less common nowadays. The diagnosis was suggested by the clinical history and confirmed by biochemical, radiologic, and histopathologic evidence. Excision of a parathyroid adenoma normalization of the metabolic status was then realized.

Effect of Losartan Treatment on the Proteinuria in Normotensive Patients Having Proteinuria due to Secondary Amyloidosis

Secondary amyloidosis (AA amyloidosis) is a well known cause of nephrotic syndrome and renal failure. Several studies in patients with nephrotic syndrome have suggested a beneficial effect of angiotensin-converting enzyme inhibitors (ACEI). Angiotensin II (ATII) receptor antagonists effect on the long term is not known. In this study, we intended to study the effect of losartan, as an ATII receptor antagonist, on proteinuria and renal functions in patients with normotensive secondary amyloidosis. In total 44 patients with biopsy proven AA amyloidosis associated with nephrotic proteinuria were included. The first group of patients (n=22) was treated with losartan 50 mg/day. The second group of patients (n=22) did not receive any specific antiproteinuric treatment. Urinary protein loss was effectively lowered by losartan from 4.38±1.0 to 2.8±0.61 g/day (p<0.0001), whereas the control group showed a slight fall in proteinuria as 4.21±1.06 to 4.12±1.07 g/day (p = 0.176). Hypoalbuminemia improved significantly from 2.52±0.69 to 2.78±0.46 g/dl (p = 0.004), in the losartan group, whereas serum albumin had fallen in the control group from 2.44±0.57 to 2.27±0.41 (p = 0.041). Serum creatinine increased in the control group from 1.52±0.42 to 2.39±0.51 mg/dl (p<0.0001), and in the losartan group from 1.59±0.50 to 1.84±0.6 mg/dl (p<0.001), after 24 months of treatment. The ATII receptor blocker losartan is effective in protecting against the progression of nephropathy due to AA amyloidosis. Symptomatic treatment of proteinuria with losartan is therefore to be considered, especially with severe proteinuria even in normotensive patients.

The role of carnitine on ovariectomy and inflammation-induced osteoporosis in rats

This study was carried out to assess the protective bone-sparing effect of carnitine with anti-inflammatory properties on chronic inflammation-induced bone loss in ovariectomised (OVX) rats. A total of 64 rats were divided into eight groups. Sixteen rats were sham-operated (SH) while the others were ovariectomised (OVX). (1) SH, (2) sham + inflammation (SHinf), (3) OVX, (4) ovariectomy + inflammation (OVXinf), (5) OVX + CAR1, (6) OVX + CAR2, (7) OVXinf + CAR1, (8) OVXinf + CAR2. After the ovariectomy surgery, all the groups (3, 4, 5, 6, 7, and 8) were allowed to recover for two months. Sixty days after the OVX, inflammation was induced by subcutaneous injections of talc in groups 2, 4, 7, and 8. Group 5 and 7 were given 50 mg/kg CAR; Group 6 and 8 were given 100 mg/kg CAR from the 60th to the 80th day. Serum levels of TNF-α, IL-1, IL-6, OP, and OC were assessed to determine inflammation and to evaluate osteoblastic activity. Bone mineral density (BMD) was assessed by dual energy X-ray absorptiometry in femur bones of rats. Carnitine administration was able to restore BMD up to values measured in both the OVX and the SH animals. The serum levels of TNF-α, IL-1β, and IL-6 were increased significantly in the OVXinf rats compared with the SH group. In OVX rats, inflammation which is evaluated by serum cytokine levels exacerbated this bone loss, as supported by values of BMD of the total femur. The two different doses of carnitine reduced bone loss and improved inflammatory biomarkers.

The effects of calcitonin on bone resorption in hyperthyroidism: a placebo-controlled clinical study

The effects of intranasal calcitonin on bone metabolism were investigated in patients with hyperthyroidism. Urinary deoxypyridinoline (uDPD) levels were measured as a bone turnover marker and lumbar spine (L2) bone mineral density (BMD) was measured by dual-energy X-ray absorptiometry (DEXA) in 7 patients who were given only antithyroid drug (group 1), in 10 patients who were given antithyroid drug plus intranasal calcitonin (group 2), and in 10 healthy subjects who were given placebo (group 3) at the beginning and at the end of the study. The study continued until the patients with hyperthyroidism became euthyroidic according to the laboratory values. This period was approximately 3 months in groups 1 and 2. At the beginning of the study, uDPD was 21.5 ± 2.6 nM DPD/mM creatinine in group 1, 23.3 ± 3.6 nM DPD/mM creatinine in group 2, and 4.3 ± 1.2 nM DPD/mM creatinine in group 3. uDPD levels measured in groups 1 and 2 were significantly higher than those in group 3 (P ≪ 0.001). Area BMD Z scores of the patients in groups 1 and 2 were significantly lower than the healthy controls (P ≪ 0.01, for both). At the end of the study, uDPD was 11.5 ± 1.6 nM DPD/mM creatinine in group 1, 5.3 ± 0.6 nM DPD/mM creatinine in group 2, and 4.4 ± 1.3 nM DPD/mM creatinine in group 3. The levels of uDPD obtained in group 1 were significantly higher than those obtained in groups 2 and 3 (P ≪ 0.05, for both). The difference between groups 2 and 3 was not significant. Area BMD Z scores measured at the end of the study were found to be increased in groups 1 and 2 compared to early values, but the values were slightly lower than the normal values. In comparison of early and late uDPD values, the decrease in late period was statistically significant in groups 1 (P ≪ 0.05) and 2 (P ≪ 0.001). We concluded that bone turnover is high in hyperthyroidism. The treatment of hyperthyroidism decreases the rate of bone turnover, but it is not sufficient to prevent the degradation of bone in hyperthyroidism. The addition of intranasal calcitonin to the treatment of hyperthyroidism prevents the degradation of bone.

Neuropad® indicator test for diagnosis of sudomotor dysfunction in type 2 diabetes

Neuropad® is a new indicator test used to diagnose sudomotor dysfunction, a component of autonomic neuropathy. In this cross-sectional study, Neuropad is evaluated and compared with corrected QT (QTc), another test used in the diagnosis of autonomic neuropathy. The indicator test measures sweat production on the basis of a color change of cobalt (II) chloride solution from blue to pink upon absorption of water. This study involved 105 patients (43 men, 62 women) with type 2 diabetes with a mean age of 56.2±11.5 y and a mean disease duration of 10.0±6.3 y. Age, sex, disease duration, glycosylated hemoglobin, and QTc were compared between patients with normal and abnormal test results. The QTc interval was measured and the new indicator test was applied in all patients. The 2 tests were compared, and the sensitivity, specificity, positive predictive value, and negative predictive value for the indicator test were calculated. Autonomie neuropathy was diagnosed in 40 patients (38.1%) with QTc interval measurement and in 72 patients (68.6%) with the new indicator test (P=.001). The sensitivity, specificity, positive predictive value, and negative predictive value for the indicator test were 87.5%, 43.1 %, 48.6%, and 84.8%, respectively. Patients with abnormal test outcomes had longer QTc than those whose test results were normal (0.433 vs 0.398 s; P=.002). Study results suggest that the new indicator test has an acceptable sensitivity but a low specificity and is not superior to other tests in the diagnosis of sudomotor dysfunction.

Retinal Nerve Fiber Layer Thickness in Early-Stage Diabetic Retinopathy With Vitamin D Deficiency.

PURPOSE To evaluate retinal nerve fiber layer (RNFL) thickness in early-stage diabetic retinopathy (DR) patients with and without vitamin D deficiency (VDD). METHODS This study compared 50 early-stage DR patients with VDD (group 1) and 50 early-stage DR patients without VDD (group 2). All patients were examined by the same ophthalmologist. Mean RNFL thickness was determined by optical coherence tomography (OCT) performed by the two independent ophthalmologists for all subjects. Vitamin D levels were measured by using a radioimmunoassay. Vitamin D deficiency was defined, in accordance with the general standards, as a 25-hydroxyvitamin D (25(OH)D) level lower than 20 ng/mL. RESULTS There were no significant differences between the groups in terms of age and sex distribution (P > 0.05). The mean serum 25(OH)D concentration of group 1 was significantly lower than that of group 2 (P < 0.001). The mean RNFL thickness of group 1 was significantly reduced compared to that of group 2 (P < 0.001). A significant relationship between the mean RNFL thickness and serum 25(OH)D concentrations was observed in group 1 (P < 0.001). CONCLUSIONS The results indicate that vitamin D functions as a neuroprotective component for optic nerves. Low serum 25(OH)D concentrations contribute to RNLF thinning in early-stage DR patients with VDD.

Primary hyperparathyroidism in pregnancy: a case series and literature review.

Abstract Primary Hyperparathyroidism (PHP) in pregnancy constitutes a serious danger to mother and fetus. The diagnosis of PHP in pregnancy presents a challenge, and PHP commonly goes unidentified and untreated in pregnancy. We present four case reports about patients having PHP, which is very rare condition in pregnancy and their treatment modalities. Three patients, not to be controlled biochemically, denied the parathyroidectomy operation although they are informed about the details of their disease. They are followed up with medical therapy. The first one had no maternal or fetal complications, the second one acquired nephrolithiasis crisis in the last trimester and the third one gave birth to a premature baby who succumbed to tetany. The fourth patient who underwent parathyroidectomy operation in the second trimester had no maternal or fetal complications. PHP in pregnancy is a preventable cause of fetal and maternal mortality and morbidity. Thus, suspecting from PHP during the pregnancy and early diagnosis is critically important in terms of maternal and fetal wellness.