Human omentin-1 reduces vascular insulin resistance and hypertension in Otsuka Long-Evans Tokushima Fatty rats.

PURPOSE: Hypertension is one of the major risk factors for renal failure and cardiovascular diseases, and is caused by various abnormalities including the contractility of blood vessels. Otsuka Long-Evans Tokushima Fatty (OLETF) rats, which mimic human type 2 diabetes, are frequently used to study obesity-induced insulin resistance (IR) and hypertension. Human omentin-1 is one of the recently identified adipocytokines. We previously demonstrated that human omentin-1 not only caused vasodilation in rat isolated blood vessels, but also prevented inflammatory responses, a possible mechanism relating IR, in human vascular endothelial cells. Taken together, we hypothesized that human omentin-1 may reduce obesity-induced IR and hypertension in OLETF rats. METHODS: OLETF rats were intraperitoneally administered with human omentin-1 for 7 days. RESULTS: Human omentin-1 had no influence on overweight, hyperglycemia, urinary glucose extraction, hyperinsulinemia, and systemic IR in OLETF rats. Human omentin-1 decreased systolic blood pressure in OLETF rats. The measurement of isometric contraction revealed that human omentin-1 had no influence on the agonist-induced contractile and relaxant responses in isolated thoracic aorta from OLETF rats. However, the relaxant response mediated by human insulin was converted into the contractile response in thoracic aorta from OLETF rats, which was prevented by human omentin-1. The Western blotting revealed that human omentin-1 improved the decrease in endothelial nitric oxide synthase activation in isolated thoracic aorta from OLETF rats. CONCLUSION: In summary, we for the first time revealed that human omentin-1 partly reduces vascular IR and thereby inhibits hypertension in OLETF rats.

Synergistic binding of DnaJ and DnaK chaperones to heat shock transcription factor σ32 ensures its characteristic high metabolic instability: implications for heat shock protein 70 (Hsp70)-Hsp40 mode of function.

Escherichia coli heat shock transcription factor σ(32) is rapidly degraded by ATP-dependent proteases, such as FtsH and ClpYQ. Although the DnaK chaperone system (DnaK, DnaJ, and GrpE) promotes σ(32) degradation in vivo, the precise mechanism that is involved remains unknown. Our previous results indicated that σ(32) mutants containing amino acid substitution in the N-terminal half of Region 2.1 are markedly stabilized in vivo. Here, we report the further characterization of these mutants by examining purified σ(32) mutants in vitro. Surprisingly, I54A σ(32), a very stable mutant, is more susceptible to ClpYQ and FtsH proteases than wild-type σ(32), indicating that the stability of σ(32) does not always reflect its susceptibility to proteases. Co-precipitation and gel filtration analyses show that purified σ(32) mutants exhibit a reduced affinity for DnaJ, leading to a marked decrease in forming a complex with DnaK in the presence of DnaJ and ATP. Other mutants with modestly increased stability (A50S σ(32) and K51E σ(32)) show an intermediate efficiency of complex formation with DnaK, suggesting that defects in binding to DnaK and DnaJ are well correlated with metabolic stability; effective interaction with DnaK promotes σ(32) degradation in vivo. We argue that the stable and effective interaction of heat shock protein 70 (Hsp70) with a substrate polypeptide may generally require the simultaneous binding of heat shock protein 40 (Hsp40) to distinct sites on the substrate.

Spinal canal enlargement procedure by restorative laminoplasty for the treatment of lumbar canal stenosis.

BACKGROUND CONTEXT: Multilevel fenestration or laminectomy is generally performed to treat the patient with lumbar canal stenosis (LCS). However, in patients requiring laminectomy, little attention has been paid to the later development of lumbar pain possibly caused by a removal of the posterior elements of the spine. In general, spinal instrumentation and fusion has been generally performed when laminectomy might cause severe postoperative spinal instability. Surgical methods where osteotomized vertebral arches are repositioned rather than removed have long been performed. However, they have never become widespread, possibly because of the complicated surgical procedures and poor postoperative arch stability, which leads to a long period of postoperative immobilization. PURPOSE: The purpose of the present report was to introduce our surgical procedures of spinal canal enlargement using restorative laminoplasty and to report the results. STUDY DESIGN/SETTING: This retrospective study was conducted to analyze the clinical results in 33 patients with lumbar canal stenosis who had been treated by our surgical procedures of spinal canal enlargement using restorative laminoplasty. PATIENT SAMPLE: Subjects were 33 patients followed for at least 2 years after surgery. Meyerding Grade I degenerative spondylolisthesis was found in 10 patients, and degenerative scoliosis of more than 5 degrees was seen in 20 patients. Nine patients demonstrated both degenerative spondylolisthesis and degenerative scoliosis. OUTCOME MEASURES: Using the Japanese Orthopedic Association (JOA) scoring system, lumbago, sciatica, leg numbness, muscle strength and gait were quantified before surgery, 1 year after surgery and at final examination (at least 2 years after surgery) to calculate improvement rates. Furthermore, correlations to age, gender, disease duration, degenerative spondylolisthesis and degenerative scoliosis were statistically analyzed. METHODS: Our surgical procedures of spinal canal enlargement using restorative laminoplasty were performed for all patients. In our procedures, posterior elements were reapplied with an absorbable fixation (poli-L-lactic acid pins). No other fusion procedure was performed jointly. RESULTS: The mean number of restored vertebral arches was 2.2, and mean surgery time was 131 minutes. Mean volume bleeding during surgery was 328.0 ml. In all patients, successful bone healing was obtained at a mean of 5 months after surgery. Mean improvement rate for the total JOA score was 80.6%. Mean improvement rates for lumbago and sciatica were 70.0% and 87.7%, respectively. Mean improvement rate for leg numbness was 50.8%. Mean improvement rates for leg muscle strength and intermittent claudication were 70.0% and 98.9%, respectively. No significant correlation was found between gender and overall improvement rate, between age and overall improvement rate, between age and leg numbness or between number of restored vertebral arches and overall improvement rate. The tendency was that the longer the disease duration, the lower the overall improvement rate, and the more severe the residual numbness. No significant correlation was found between disease duration and muscle strength or lumbago.A significant correlation was not found between the presence of preoperative Grade I degenerative spondylolisthesis and overall improvement rate or lumbago. However, a significant difference in severity of lumbago existed between patients with degenerative scoliosis of 9 degrees and below and those with degenerative scoliosis of 10 degrees and above. CONCLUSIONS: Our surgical procedures of spinal canal enlargement using restorative laminoplasty produce complete decompression and anatomical reconstruction of the posterior elements, ligaments and muscles. Improvement in complaints of lumbago may be a consequence of the anatomical reconstruction of the posterior spinal elements. Overall, favorable results were obtained. The best results were obtained if surgery is performed within 2 years of the onset of LCS.