Estrogen receptors in skeletal metabolism: lessons from genetically modified models of receptor function

Estrogens have long been known to be important for skeletal homeostasis, but their precise mechanisms of action in bone are still unclear. Mice with targeted deletions of the estrogen receptors alpha (ERalpha) and beta (ERbeta) have been generated by two research groups and several studies performed characterizing the phenotype of ERalpha knockout (ERKOalpha), ERbeta knockout (ERKObeta), or double deletion of ERalpha and ERbeta (DERKO) mice. Initial studies reported a reduction in bone mineral density in male ERKOalpha mice. More extensive analyses have been puzzling, likely because of compensatory mechanisms in ERKO mice. Furthermore, the existence of a third ER continues to be a potential explanation for some actions of estrogen in bone. Other rodent models, including the testicular feminized mouse and rat, the aromatase knockout mouse, and a rat with a dominant negative ER mutation, have added information regarding estrogen's actions in bone. This review summarizes many reports characterizing available rodent models with genetic alterations relevant to estrogen action. The sum of these reports suggests that the ERbeta is not highly protective in bone because loss of its function results in minimal alterations in the skeleton. Furthermore, loss of both the ERalpha and the ERbeta does not account for loss of estrogen action in bone, because the impact of DERKO is seemingly not as great as the impact of gonadectomy on the skeleton. Finally, through studies of ERKO mice and other rodent models of altered sex steroid action, it appears that estrogen may be more protective in the skeleton than androgens.     

What evidence is there for the existence of individual genes with antagonistic pleiotropic effects?

Classical evolutionary theory predicts the existence of genes with antagonistic effects on longevity and various components of early-life fitness. Quantitative genetic studies have provided convincing evidence that such genes exist. However, antagonistic pleiotropic effects have rarely been attributed to individual loci. We examine several classes of longevity-assurance genes: those involved in regulation of the gonad; the insulin-like growth factor pathway; free-radical scavenging; heat shock proteins and apoptosis. We find initial evidence that antagonistic pleiotropic effects are pervasive in each of these classes of genes and in various model systems--although most studies lack explicit studies of fitness components. This is particularly true of human studies. Very little is known about the early-life fitness effects of longevity loci. Given the possible medical importance of such effects we urge their future study.     

Is it safe to use a thermocautery device for circumcision? Examination of the histopathological changes emerging after thermocautery-assisted circumcisions

Multiple number of techniques and devices have been described concerning circumcision method so far. One of them is thermocautery device, and it has been widely used. Although there is controversy that the penis may be damaged due to the heat generated during the use of the device, not enough histopathological studies have been conducted. We aimed to determine the histopathological changes in human foreskin caused by heat after circumcision with thermocautery and to demonstrate the safety of the use of a thermocautery-assisted circumcision. Forty-one patients were divided into two groups according to the thermal energy used during cutting with thermocautery as follows: high temperature (Group 1, n = 22) and low temperature (Group 2, n = 19). The effect of the heat intensity and depth of the coagulation necrosis produced with thermocautery-assisted circumcisions performed at low and high temperatures were evaluated. The difference between the groups was not statistically significant. Tissue damage is extremely limited in thermocautery-assisted circumcisions, even when it is used at high temperatures. The thermocautery device can be used for effective and safe circumcisions.     

A New Approach to Tertiary Hyperparathyroidism: Percutaneous Embolization: Two Case Reports

Secondary hyperparathyroidism is one of the most common complications of chronic kidney failure. If prolonged, parathyroid hormone release gains autonomy and tertiary hyperparathyroidism with parathyroid adenoma or hyperplasia can be develop. Tertiary hyperparathyroidism is associated with increased risk of mortality and morbidity; thus, treatment is recommended. Medical treatment includes phosphate binders, vitamin D analogues, and calcimimetic agents. Most cases of tertiary hyperparathyroidism can be controlled with medical treatment. When medical treatment options prove insufficient, parathyroidectomy is recommended. However, recurrence after parathyroidectomy is possible, which requires an alternative treatment. We present our percutaneous embolization experience, which has not been tried in the treatment of tertiary hyperparathyroidism in renal transplantation patients diagnosed with tertiary hyperparathyroidism.     

Left atrioventricular valve repair technique in partial atrioventricular septal defects

BACKGROUND: The aim of our study was to evaluate the effect of chordal transfer around the cleft on left atrioventricular valve competence in the late postoperative period. METHODS: Forty-four adult patients underwent surgical correction of partial atrioventricular septal defect between 1983 and 1997. Fenestration was found in 8 patients (18.2%) and cleft, in 35 (79.5%). There was no chordal support of the free edges of the left superior and left inferior leaflets around the cleft in 18 patients. Two chordae were mobilized from the left lateral leaflet and reimplanted into the tip of the left superior and left inferior leaflets around the cleft. RESULTS: At 5 years postoperatively, left atrioventricular valve insufficiency was severe in 5 patients and moderate in 11 patients who had had cleft closure alone. In contrast, severe valvular insufficiency was present in only 1 patient in the group with chordal transfer (p < 0.05). Reoperation was done in 5 patients with isolated cleft closure. Left AV valve replacement was performed in 1 patient. CONCLUSIONS: Chordal transfer plus cleft closure with interrupted sutures significantly reduces early and late left atrioventricular valve incompetence and also decreases the rate of reoperation.     

Evaluation of Serum microRNA Let-7c and Let-7d as Predictive Biomarkers for Metastatic Pancreatic Cancer

Background:First-line treatments for metastatic pancreatic cancer are chemotherapy regimens consisting of 5-fluorouracil or gemcitabine; however, there are no biomarkers to help determine which patients might benefit from which treatment regimens. We aimed to show that microRNAs let-7c and 7d can be used as independent predictive biomarkers for metastatic pancreatic cancer.Methods:A total of 55 patients who had first-line chemotherapy with FOLFIRINOX or gemcitabine + capecitabine were included. Patients were divided into groups based on let-7c and let-7d levels and chemotherapy treatment as let-7c-7d high FOLFIRINOX, let-7c-7d high gemcitabine + capecitabine, let-7c-7d low FOLFIRINOX, and let-7c-7d low gemcitabine + capecitabine. Blood samples were taken from patients before chemotherapy for microRNA let-7c and 7d analysis. MicroRNA isolation was performed using a miRNeasy Serum/Plasma Kit and identified using spectrophotometric measurements. After isolation, microRNA was converted to cDNA using a microRNA cDNA Synthesis Kit with poly (A) polymerase tailing. The expression of microRNA was examined using quantitative real-time polymerase chain reaction.Results:The overall survival of patients who received FOLFIRINOX treatment with a high let-7c-7d level was statistically significantly longer than those who received gemcitabine + capecitabine with a high let-7c-7d level. In addition, patients with low let-7c expression receiving FOLFIRINOX progressed significantly 2.104 times earlier than patients with high let-7c expression receiving FOLFIRINOX.Conclusion:The serum MicroRNA let-7c level was found to be an independent predictive biomarker in the FOLFIRINOX treatment group.