Time filter

Source Type

Gozlan Y.,Jesse Z and Sara Lea Shafer Institute for Endocrinology and Diabetes | Gozlan Y.,Tel Aviv University | Tenenbaum A.,Jesse Z and Sara Lea Shafer Institute for Endocrinology and Diabetes | Shalitin S.,Jesse Z and Sara Lea Shafer Institute for Endocrinology and Diabetes | And 9 more authors.
Pediatric Diabetes | Year: 2012

Background: Maturity-onset diabetes of the young (MODY) is characterized by an autosomal dominant mode of inheritance; a primary defect in insulin secretion with non-ketotic hyperglycemia, age of onset under 25 yr; and lack of autoantibodies. Heterozygous mutations in glucokinase (GCK) are associated with mild fasting hyperglycemia and gestational diabetes mellitus while homozygous or compound heterozygous GCK mutations result in permanent neonatal diabetes mellitus. Given that both the Israeli-Arabic and the various Israeli-Jewish communities tend to maintain ethnic seclusion, we speculated that it would be possible to identify a relatively narrow spectrum of mutations in the Israeli population. Objective: To characterize the genetic basis of GCK-MODY in the different ethnic groups of the Israeli population. Subjects: Patients with clinically identified GCK-MODY and their first degree family members. Methods: Molecular analysis of GCK was performed on genomic DNA using polymerase chain reaction, denaturing gradient gel electrophoresis (DGGE), and sequencing. Bioinformatic model was preformed using the NEST program. Results: Mutations in GCK were identified in 25 families and were all family-specific, except c.616A>C. p.T206P. This mutation was identified in six unrelated families, all patients from a Jewish-Ashkenazi descent, thus indicating an ethno-genetic correlation. A simple, fast, and relatively cheap DGGE/restriction-digestion assay was developed. Conclusions: The high incidence of the mutant allele in GCK-MODY patients of Jewish-Ashkenazi descent suggests a founder effect. We propose that clinically identified GCK-MODY patients of Jewish-Ashkenazi origin be first tested for this mutation. © 2011 John Wiley & Sons A/S.


Massarwi M.,Felsentein Medical Research Center | Massarwi M.,Tel Aviv University | Gat-Yablonski G.,Felsentein Medical Research Center | Gat-Yablonski G.,Tel Aviv University | And 8 more authors.
American Journal of Emergency Medicine | Year: 2013

Background The use of protein- and peptide-based drugs in the treatment of disease has significantly increased in recent years. However, their chemical and physical properties make them unsuitable for simple oral delivery. Objective The objective of this proof-of-concept study was to examine the feasibility of protein administered via intraosseous (IO) injection. Human growth hormone (GH), a 22-kd protein, served as the model protein. Results An indwelling IO needle and intravenous (IV) line were placed in four New Zealand white male rabbits, and 50, 100, 200, or 400 μg/kg of GH were injected. Blood samples were taken at different time points and analyzed for GH concentration. There were no significant pharmacokinetic differences between the IO and IV routes. For the 400 μg/kg dose, the area under the serum GH concentration time curve was 100.55 ± 46.7 μg/min*mL with IV administration and 84.6 ± 34 μg/min*mL for IO (P =.73 compared to the IV route), Cmax measured 11.2 ± 5 μg/L and Tmax 0.9 ± 0.7 minutes. For the 200 μg/kg dose, the area under the curve was 68.5 ± 16.7 μg/min*mL with IV administration, and 85.1 ± 1.5 μg/min*mL (P =.39) for IO, Cmax measured 8.13 ± 2.44 μg/L and Tmax 1.92 ± 1.06 minutes. Conclusions The findings confirm that a large protein (22 kd) can be administered via IO injection, reaching blood levels comparable to IV injection. Further studies with a larger number of animals are required to evaluate the pharmacokinetics and pharmacodynamics of high-molecular-weight proteins injected by the IO route. © 2013 Elsevier Inc.


Shtaif B.,Felsentein Medical Research Center | Shtaif B.,Tel Aviv University | Dror N.,Jesse Z and Sara Lea Shafer Institute for Endocrinology and Diabetes | Bar-Maisels M.,Felsentein Medical Research Center | And 7 more authors.
Growth Factors | Year: 2015

Growth without growth hormone (GH) is often observed in the setup of obesity; however, the missing link between adipocytes and linear growth was until now not identified. 3T3L1 cells were induced to differentiate into adipocytes and their conditioned medium (CM) (adipocytes CM, CMA) was added to metatarsals bone culture and compared to CM derived from undifferentiated cells. CMA significantly increased metatarsals bone elongation. Adipogenic differentiation increased the expression of growth and differentiation factor (GDF)-5, also found to be secreted into the CMA. GDF-5 significantly increased metatarsal length in culture; treatment of the CMA with anti-GDF-5 antibody significantly reduced the stimulatory effect on bone length. The presence of GDF-5 receptor (bone morphogenetic protein receptor; BMPR1) in metatarsal bone was confirmed by immunohistochemistry. Animal studies in rodents subjected to food restriction followed by re-feeding showed an increase in GDF-5 serum levels concomitant with nutritional induced catch up growth. These results show that adipocytes may stimulate bone growth and suggest an additional explanation to the growth without GH phenomenon. © 2015 Taylor and Francis.


De Vries L.,Jesse Z and Sara Lea Shafer Institute for Endocrinology and Diabetes | De Vries L.,Tel Aviv University | Gat-Yablonski G.,Jesse Z and Sara Lea Shafer Institute for Endocrinology and Diabetes | Gat-Yablonski G.,Tel Aviv University | And 6 more authors.
Human Reproduction | Year: 2014

Central precocious puberty may be familial in about a quarter of the idiopathic cases. However, little is known about the genetic causes responsible for the disorder. In this report we describe a family with central precocious puberty associated with a mutation in the makorin RING-finger protein 3 (MKRN3) gene. A novel missense mutation (p.H420Q) in the imprinted MKRN3 gene was identified in the four affected siblings, in their unaffected father and in his affected mother. An in silico mutant MKRN3 model predicts that the mutation p.H420Q leads to reduced zinc binding and, subsequently, impaired RNA binding. These findings support the fundamental role of the MKRN3 protein in determining pubertal timing. © The Author 2014. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology.


Meydan C.,Chaim Sheba Medical Center | Meydan C.,Tel Aviv University | Goldstein N.,Felsentein Medical Research Center | Goldstein N.,Tel Aviv University | And 11 more authors.
Obesity Surgery | Year: 2015

Background: Although laparoscopic sleeve gastrectomy (LSG) has been shown to have a long-term antidiabetic effect, little is known regarding the immediate response to surgery. This study’s objective was to evaluate the glycemic and lipid metabolic response in the first postoperative week. Methods: The study included 21 obese diabetic participants. Glycemic markers, lipids, and hepatic function tests were measured just prior to surgery and at 1 week and 3 months postoperatively. Two participants were dropped prior to all measurements due to technical reasons, and two more were lost to follow-up. Results: At 1 week after surgery, compared to preoperative baseline, we found reduced hemoglobin A1c (7.63 to 7.31, P < 0.001), insulin (24.96 to 10.92, P < 0.05), and borderline significant homeostatic model assessment insulin resistance (HOMA-IR, 9.48 to 3.91, P > 0.05). Low-density lipoprotein (LDL) cholesterol increased and high-density lipoprotein (HDL) cholesterol decreased. Three months after surgery, hemoglobin A1c, insulin, and HOMA-IR continued to decrease (6.05, 7.11, and 1.92, respectively, P < 0.05), with hemoglobin A1c correlated to weight loss (P < 0.05). Triglycerides, triglyceride to HDL ratio, and total cholesterol to HDL ratio also decreased, but there was no significant change in LDL cholesterol or HDL versus presurgery levels. Reduced triglyceride levels were correlated with reduced alanine transaminase (ALT) and gamma-glutamyl transpeptidase (GGT) (P < 0.05). Conclusions: LSG is associated with marked antidiabetic effects as early as 1 week after surgery, unrelated to weight loss. The antidiabetic effect improves at 3 months. Triglyceride reduction was associated with improved hepatic functions, but cholesterol did not show a meaningful reduction. © 2015, Springer Science+Business Media New York.


Uziel O.,Felsentein Medical Research Center | Laish I.,Meir Medical Center | Bulcheniko M.,Felsentein Medical Research Center | Bulcheniko M.,Tel Aviv University | And 7 more authors.
Annals of Transplantation | Year: 2013

Background: Telomeres are non-coding regions of DNA that cap the ends of chromosomes. Their length is considered a marker of human replicative senescence and premature aging. Given the high association of liver transplantation with the metabolic syndrome, we hypothesized that liver transplant recipients may exhibit premature and accelerated aging. Material/Methods: Telomere length in peripheral blood lymphocytes was measured by polymerase chain reaction in 62 consecutive liver-transplant recipients and 59 healthy control subjects aged 20-76 years. Clinical and laboratory parameters were collected from the medical files. Results: The liver transplant recipients were significantly older than the control subjects (p=0.012), with significantly higher rates of obesity (BMI >30 kg/m2), dyslipidemia, hypertension, diabetes, and fatty liver. Mean telomere length was significantly shorter in the transplant group (0.59±0.6 vs. 1.91±1.78 in the controls, p<0.0001). Within the transplant group, there was no significant association between mean telomere length and underlying liver disease or presence of the metabolic syndrome or its constituents. On multivariate analysis, telomere length was negatively associated with patient age (p=0.0001), male sex (p=0.04), acute rejection (p=0.005), and fatty liver (p=0.009), and was positively associated with time from transplantation (p=0.006). Conclusions: Liver transplantation is associated with shortened telomere length in peripheral blood lymphocytes, suggesting accelerated senescence. © Ann Transplant.


PubMed | Felsentein Medical Research Center and Chaim Sheba Medical Center
Type: Journal Article | Journal: Obesity surgery | Year: 2015

Although laparoscopic sleeve gastrectomy (LSG) has been shown to have a long-term antidiabetic effect, little is known regarding the immediate response to surgery. This studys objective was to evaluate the glycemic and lipid metabolic response in the first postoperative week.The study included 21 obese diabetic participants. Glycemic markers, lipids, and hepatic function tests were measured just prior to surgery and at 1 week and 3 months postoperatively. Two participants were dropped prior to all measurements due to technical reasons, and two more were lost to follow-up.At 1 week after surgery, compared to preoperative baseline, we found reduced hemoglobin A1c (7.63 to 7.31, P<0.001), insulin (24.96 to 10.92, P<0.05), and borderline significant homeostatic model assessment insulin resistance (HOMA-IR, 9.48 to 3.91, P>0.05). Low-density lipoprotein (LDL) cholesterol increased and high-density lipoprotein (HDL) cholesterol decreased. Three months after surgery, hemoglobin A1c, insulin, and HOMA-IR continued to decrease (6.05, 7.11, and 1.92, respectively, P<0.05), with hemoglobin A1c correlated to weight loss (P<0.05). Triglycerides, triglyceride to HDL ratio, and total cholesterol to HDL ratio also decreased, but there was no significant change in LDL cholesterol or HDL versus presurgery levels. Reduced triglyceride levels were correlated with reduced alanine transaminase (ALT) and gamma-glutamyl transpeptidase (GGT) (P<0.05).LSG is associated with marked antidiabetic effects as early as 1 week after surgery, unrelated to weight loss. The antidiabetic effect improves at 3 months. Triglyceride reduction was associated with improved hepatic functions, but cholesterol did not show a meaningful reduction.

Loading Felsentein Medical Research Center collaborators
Loading Felsentein Medical Research Center collaborators