Identification of SLC22A5 Gene Mutation in a Family with Carnitine Uptake Defect.

Primary systemic carnitine deficiency is caused by homozygous or compound heterozygous mutation in the SLC22A5 gene on chromosome 5q31. The most common presentations are in infancy and early childhood with either metabolic decompensation or cardiac and myopathic manifestations. We report a case of 9-year-old boy with dysmorphic appearance and hypertrophic cardiomyopathy. Tandem MS spectrometry analysis was compatible with carnitine uptake defect (CUD). His sister had died due to sudden infant death at 19 months. His second 4-year-old sister's echocardiographic examination revealed hypertrophic cardiomyopathy, also suffering from easy fatigability. Her tandem MS spectrometry analyses resulted in CUD. We sequenced all the exons of the SLC22A5 gene encoding the high affinity carnitine transporter OCTN2 in the DNA. And one new mutation (c.1427T>G → p.Leu476Arg) was found in the boy and his sister in homozygous form, leading to the synthesis of an altered protein which causes CUD. The parent's molecular diagnosis supported the carrier status. In order to explore the genetic background of the patient's dysmorphic appearance, an array-CGH analysis was performed that revealed nine copy number variations only. Here we report a novel SLC22A5 mutation with the novel hallmark of its association with dysmorphologic feature.

Mutations in BTD gene causing biotinidase deficiency: a regional report.

Biotinidase deficiency is an autosomal recessive inborn error of biotin metabolism. Children with biotinidase deficiency cannot cleave biocytin and, therefore, cannot recycle biotin. Untreated individuals become secondarily biotin deficient, which in turn results in decreased activities of the biotin-dependent carboxylases and the subsequent accumulation of toxic metabolites causing clinical symptoms. Biotinidase deficiency is characterized by neurological, cutaneous manifestations and metabolic abnormalities. The worldwide incidence of profound biotinidase deficiency has been estimated at 1:112,271. The human biotinidase gene is located on chromosome 3p25 and consists of four exons with a total length of 1629 base pairs. To date, more than 100 mutations in the biotinidase gene known to cause biotinidase deficiency have been reported. The vast majority of mutations are homozygous or compound heterozygous. Finding known mutations can be correlated with the biochemical enzymatic results. This report summarizes the demographic features of patients identified as biotinidase deficient from August of 2012 through August of 2013 and mutation analysis results for 20 cases in the southeast region of Turkey.

Morphometric changes in the endometrium and serum leptin levels during the implantation period of the embryo in the rat in response to exogenous ovarian stimulation.

OBJECTIVE: To determine the changes in endometrium and serum leptin levels during the periimplantation period of the ovum in the rat in response to exogenous ovarian stimulation by hMG and recombinant FSH (rFSH). DESIGN: Experimental animal study. SETTING: University hospital. INTERVENTION(S): A total of 100 female rats were stimulated with low and high doses of hMG (groups 1 and 2, respectively) and low and high doses of rFSH (groups 3 and 4, respectively) before mating after the regular cycle was observed. The control group of animals was not injected (group 5). The endometrium of the pregnant rats (n = 53) was analyzed by the morphometric method, and serum samples were obtained for leptin and E2 levels at baseline and on the day of implantation. The mitotic index was determined separately for endometrial surface, glandular epithelium, and endometrial stroma by light microscope. MAIN OUTCOME MEASURE(S): Morphometric analysis of endometrium, mitotic index, and serum leptin and E2 levels RESULT(S): The mean number of corpora lutea was significantly higher in groups 2 and 4. The measurement of mucosal depth was found to be significantly higher in group 4 compared with the control group (0.361 +/- 0.03 vs. 0.289 +/- 0.04). The depth of the endometrial surface epithelium was found to be significantly higher in all study groups (groups 1-4) compared with the control group. The depth of the surface epithelium was found to be significantly lower in group 1 compared with the other study groups (groups 2, 3, and 4). The depth of the surface epithelium was also significantly lower in group 2 compared with group 3 (21.58 +/- 3.56 vs. 28.21 +/- 3.56). Mitotic indices that were determined at the endometrial surface epithelium and stroma were all significantly lower in all study groups (groups 1-4) compared with the control group. There was no significant increase for the baseline leptin levels compared with the levels measured on the day of implantation. CONCLUSION(S): In an animal model, exogenous administration of gonadotropins significantly affects the morphology of the endometrium and the mitotic index in the implantation period of the embryo. These morphological effects become more pronounced as we increase the administered dose of exogenous gonadotropins. However, no differences in leptin levels were observed relative to different gonadotropin type and dose regimens.

Constructive effect of exogenous melatonin against osteoporosis after ovariectomy in rats.

OBJECTIVE: To analyze histomorphometric, densitometric and biochemical effects of melatonin on osteoporosis in ovariectomized rats. STUDY DESIGN: Wistar rats were divided into 6 groups. Group C: control; Group I: bilateral ovariectomy (OVX); Group II: OVX + vehicle; Group III: OVX + 10 mg/kg/day melatonin (MLT); Group IV: OVX + 30 mg/kg/day MLT; Group V: sham + 10 mg/kg/day MLT. Cortex, trabecula, osteoblast and osteoclast numbers were evaluated on vertebra and femur histomorphometrically. Hydroxyproline analysis was used to determine collagen content of femur and vertebrae. Bone mineral density and bone mineral content were measured. RESULTS: Trabecular thickness and trabecular area of vertebra and femur and cortical thickness of femur showed remarkable decrease after OVX, but increased after MLT treatment in the OVX+MLT groups. Following OVX, no statistically significant difference was found in number of osteoblasts or osteoclasts, trabecular number or levels of hydroxyproline after treatment with MLT. OVX caused significant decrease in bone mineral density, but treatment with MLT was unable to reverse this effect. CONCLUSION: MLT may trigger microscopic changes in bone, and time of application is critical for clinical recovery. It can be effective in helping treat postmenopausal osteoporosis. However, it is contraindicated in women who have normal-functioning ovaries.

Does tibolone affect serum leptin levels and body weight in postmenopausal women?

OBJECTIVES: Leptin has a significant role in body weight regulation and energy balance. We examined the effect of tibolone on the body weight and serum leptin levels in postmenopausal women. STUDY DESIGN: Twenty women (aged 43-60 years) participated in this prospective study. All women in this study protocol received 2.5 mg/day of tibolone. Absolute and body mass index (BMI)-corrected serum leptin concentrations and BMI values were measured at baseline, after 3 months, and after 6 months of the tibolone therapy. RESULTS: Tibolone did not affect absolute and BMI-corrected serum leptin levels, and BMI values during the treatment. A significant linear correlation between BMI values and serum leptin levels was observed (p<0.05, r=0.67). CONCLUSIONS: Tibolone seems not to affect serum leptin levels, body weight and BMI values of postmenopausal women. There is a significant correlation between serum leptin levels and BMI values.

Increased excretions of glycosaminoglycans and heparan sulfate in lupus nephritis and rheumatoid arthritis.

Urinary glycosaminoglycans (GAG) and heparan sulfate (HS) are considered to be markers of early renal involvement. This study was undertaken to demonstrate their excretion patterns in rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) with and without arthritis. Serum creatinine and urinary GAG, HS, microalbumin, and creatinine measurements were made in 51 biopsy-proven lupus nephritis (LN) cases, 12 RA patients, and 21 healthy controls. Urinary GAG and HS levels were higher in the LN and RA groups than in controls. Heparan sulfate excretions and SLE disease activity index (SLEDAI) scores were no different between SLE patients with classes 1 and 2 (group A) and those with classes 3, 4, and 5 (group B) renal involvement. However, GAG and microalbumin excretions were significantly high in the latter. There were no differences in GAG and HS excretions between normoalbuminuric, microalbuminuric, and macroproteinuric SLE patients or between those with and without arthritis. In conclusion, urinary GAG and HS, being unrelated to the presence of arthritis, are independent markers of LN. Extrarenal causes or subclinical renal involvement may be responsible in RA due to their increased excretion in these patients.

Effects of pentoxifylline on alcohol-induced gastric injury and acid secretion in rats.

We aimed to evaluate the protective effects of pentoxifylline on alcohol-induced gastric injury, its relation with nitric oxide and prostaglandin synthesis, as well as gastric acidity in rats. Acute gastric mucosal injury was induced by intragastric infusion of 2 ml 98% alcohol. Pentoxifylline was given at 100 mg/kg intraperitoneally. Indomethacin and N(G)-nitro-L arginine were used to inhibit prostaglandin and nitric oxide synthesis, respectively. Macroscopic and microscopic gastric injuries were evaluated. Gastric pH, tissue malondialdehyde levels, oxidized and reduced glutathion (GSSG/GSH) levels, and effects of pentoxifylline on gastric acid output were measured. Pentoxifylline pretreatment significantly reduced macroscopic and microscopic gastric injury. Malondialdehyde level was lower in pentoxifylline treated rats (351.1 +/- 94.1 nmol/g vs 624.3 +/- 234.2 nmol/g). Pentoxifylline has a protective role on alcohol-induced gastric mucosal injury in rats. This effect is not related to synthesis of prostaglandins and changes in gastric acidity but does seem to be related to nitric oxide-mediated pathways. In contrast, pentoxifylline increases gastric acid output significantly.