Vav1 inhibits RANKL-induced osteoclast differentiation and bone resorption

Vav1 is a Rho/Rac guanine nucleotide exchange factor primarily expressed in hematopoietic cells. In this study, we investigated the potential role of Vav1 in osteoclast (OC) differentiation by comparing the ability of bone marrow mononuclear cells (BMMCs) obtained from Vav1-deficient (Vav1−/−) and wild-type (WT) mice to differentiate into mature OCs upon stimulation with macrophage colony stimulating factor and receptor activator of nuclear kappa B ligand in vitro. Our results suggested that Vav1 deficiency promoted the differentiation of BMMCs into OCs, as indicated by the increased expression of tartrate-resistant acid phosphatase, cathepsin K, and calcitonin receptor. Therefore, Vav1 may play a negative role in OC differentiation. This hypothesis was supported by the observation of more OCs in the femurs of Vav1−/− mice than in WT mice. Furthermore, the bone status of Vav1−/− mice was analyzed in situ and the femurs of Vav1−/− mice appeared abnormal, with poor bone density and fewer number of trabeculae. In addition, Vav1-deficient OCs showed stronger adhesion to vitronectin, an αvβ3 integrin ligand important in bone resorption. Thus, Vav1 may inhibit OC differentiation and protect against bone resorption

A case of primary aldosteronism combined with acquired nephrogenic diabetes insipidus

AbstractAldosterone-producing adrenal adenoma can induce various clinical manifestations as a result of chronic exposure to aldosterone. We report a rare case of a 37-year-old man who complained of general weakness and polyuria. He was diagnosed with aldosterone-producing adrenal adenoma and nephrogenic diabetes insipidus. Aldosterone enhances the secretion of potassium in the collecting duct, which can lead to hypokalemia. By contrast, nephrogenic diabetes insipidus, which manifests as polyuria and polydipsia, can occur in several clinical conditions such as acquired tubular disease and those attributed to toxins and congenital causes. Among them, hypokalemia can also damage tubular structures in response to vasopressin. The patient’s urine output was >3 L/d and was diluted. Owing to the ineffectiveness of vasopressin, we eventually made a diagnosis of nephrogenic diabetes insipidus. Laparoscopic adrenalectomy and intraoperative kidney biopsy were subsequently performed. The pathologic finding of kidney biopsy revealed a decrease in aquaporin-2 on immunohistochemical stain

Dapagliflozin Does Not Protect against Adriamycin-Induced Kidney Injury in Mice

Introduction: Sodium-glucose cotransporter 2 (SGLT2) inhibitors target SGLT2 in renal proximal tubules and promote glycosuria in type 2 diabetes mellitus in humans and animal models, resulting in reduced blood glucose levels. Although clinical trials have shown that SGLT2 inhibitors attenuate the progression of chronic kidney disease, there have been concerns regarding SGLT2-induced acute kidney injury. In this study, we investigated the effect of SGLT2 inhibitors on adriamycin-induced kidney injury in mice. Methods: Seven-week-old balb/c mice were injected with adriamycin 11.5 mg/kg via the tail vein. Additionally, dapagliflozin was administered via gavage for 2 weeks. The mice were divided into five groups: vehicle, dapagliflozin 3 mg/kg, adriamycin, adriamycin plus dapagliflozin 1 mg/kg, and adriamycin plus dapagliflozin 3 mg/kg. Results: Adriamycin injection reduced the body weight and food and water intakes. Dapagliflozin also decreased the body weight and food and water intakes. Fasting blood glucose and urine volume were not altered by either adriamycin or dapagliflozin. Once adriamycin-induced kidney injury had developed, there were no differences in systolic blood pressure among the groups. Dapagliflozin did not alleviate proteinuria in adriamycin-induced kidney injury. Adriamycin induced significant glomerular and interstitial injury, but dapagliflozin did not attenuate these changes in renal injury. Interestingly, SGLT2 expressions were different between the cortex and medulla of kidneys by dapagliflozin treatment. Dapagliflozin increased SGLT2 expression in medulla, not in cortex. Conclusion: Dapagliflozin had no effect on proteinuria or inflammatory changes such as glomerular and tubular damages in adriamycin-induced kidney injury. Our study suggests that dapagliflozin does not protect against adriamycin-induced kidney injury. More experimental studies regarding the effects of SGLT2 inhibitors on various kidney diseases are needed to clarify the underlying mechanisms

Osteogenic Differentiation Potential in Parthenogenetic Murine Embryonic Stem Cells

Embryonic stem cells have a pluripotency and a potential to differentiate to all type of cells. In our previous study, we have shown that embryonic stem cells (ESCs) lines can be generated from murine parthenogenetic embryos. This parthenogenetic ESCs line can be a useful stem cell source for tissue repair and regeneration. The defect in full-term development of parthenogenetic ESCs line enables researchers to avoid the ethical concerns related with ESCs research. In this study, we presented the results demonstrating that parthenogenetic ESCs can be induced into osteogenic cells by supplementing culture media with ascorbic acid and ß-glycerophosphate. These cells showed morphologies of osteogenic cells and it was proven by Von Kossa staining and Alizarin Red staining. Expression of marker genes for osteogenic cells (osteopontin, osteonectin, alkaline phosphatase, osteocalcin, bone-sialoprotein, collagen type1, and Cbfa1) also confirmed osteogenic potential of these cells. These results demonstrate that osteogenic cells can be generated from parthenogenetic ESCs in vitro

The Effects of Changing from Isoflurane to Desflurane on the Recovery Profile during the Latter Part of Anesthesia

It is not known whether changing from isoflurane to desflurane during the latter part of anesthesia shows early emergence and recovery in long surgery. We therefore evaluated the effects of changing isoflurane to desflurane on emergence and recovery. Eighty-two patients were randomly assigned to receive isoflurane (Group I) or desflurane (Group D) or to change from isoflurane to desflurane anesthesia (Group X). At the point when there was an hour until the operation would end, isoflurane was replaced with 1 MAC of desflurane in Group X, and isoflurane and desflurane were maintained at 1 MAC in Groups I and D. When the operation ended, we compared the emergence and recovery characteristics among the 3 groups. Compared with Group I, Group X showed faster emergence and recovery. Group X and Group D showed similar emergence and recovery. In conclusion, changing isoflurane to desflurane during the latter part of anesthesia improves emergence and recovery

Patterns of Post-thyroidectomy Hemorrhage

ObjectivesPostoperative hemorrhage is a potentially life-threatening complication in thyroid surgery. This study was performed to review the clinical patterns of post-thyroidectomy hemorrhage, and especially as they are related to the source of bleeding.MethodsWe performed a retrospective review of 10 patients (0.96%) with post-thyroidectomy hemorrhage that required surgical evacuation. The clinical patterns such as the time interval from surgery to hemorrhage and the signs and symptoms according to the bleeding focus were evaluated.ResultsThe mean time interval from surgery to symptom onset was 7 hr 52 min. Six cases showed bleeding deep to the strap muscles, while the other 4 cases showed bleeding superficial to the muscles. Ecchymosis was prominent and dark in color in 3 of the 4 cases (75%) of superficial bleeding, however it was identified in only 2 of the 6 cases (33%) of deep bleeding. Respiratory distress occurred in two cases of hematoma deep to the strap muscles, but in none of the cases with superficial bleeding.ConclusionThe post-thyroidectomy hemorrhage had some different clinical patterns between the superficial cases and the deep cases, showing that life-threatening airway obstruction occurred from the deep hematoma. A thorough understanding of the clinical patterns of post-thyroidectomy hemorrhage between the cases of superficial and those cases of deep hematoma may provide valuable surgical tips to manage this potentially lethal complication

Total intravenous anesthesia with propofol and remifentanil in a patient with MELAS syndrome -A case report-

A 23-year-old woman with MELAS (mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes) underwent a laparoscopy-assisted appendectomy. MELAS syndrome is a multisystemic disease caused by mitochondrial dysfunction. General anesthesia has several potential hazards to patients with MELAS syndrome, such as malignant hyperthermia, hypothermia, and metabolic acidosis. In this case, anesthesia was performed with propofol, remifentanil TCI, and atracurium without any surgical or anesthetic complications. We discuss the anesthetic effects of MELAS syndrome