Effect of transcranial direct current stimulation on short-term and long-term treatment of chronic tinnitus

Objective

This study was conducted to investigate the effectiveness of anodal and cathodal methods in reducing the intensity of tinnitus and to compare them with the control.

Therapeutic Effects of FGF23 c‐tail Fc in a Murine Preclinical Model of X‐Linked Hypophosphatemia Via the Selective Modulation of Phosphate Reabsorption

Fibroblast growth factor 23 (FGF23) is the causative factor of X‐linked hypophosphatemia (XLH), a genetic disorder effecting 1:20,000 that is characterized by excessive phosphate excretion, elevated FGF23 levels and a rickets/osteomalacia phenotype. FGF23 inhibits phosphate reabsorption and suppresses 1α,25‐dihydroxyvitamin D (1,25D) biosynthesis, analytes that differentially contribute to bone integrity and deleterious soft‐tissue mineralization. As inhibition of ligand broadly modulates downstream targets, balancing efficacy and unwanted toxicity is difficult when targeting the FGF23 pathway. We demonstrate that a FGF23 c‐tail‐Fc fusion molecule selectively modulates the phosphate pathway in vivo by competitive antagonism of FGF23 binding to the FGFR/α klotho receptor complex. Repeated injection of FGF23 c‐tail Fc in Hyp mice, a preclinical model of XLH, increases cell surface abundance of kidney NaPi transporters, normalizes phosphate excretion, and significantly improves bone architecture in the absence of soft‐tissue mineralization. Repeated injection does not modulate either 1,25D or calcium in a physiologically relevant manner in either a wild‐type or disease setting. These data suggest that bone integrity can be improved in models of XLH via the exclusive modulation of phosphate. We posit that the selective modulation of the phosphate pathway will increase the window between efficacy and safety risks, allowing increased efficacy to be achieved in the treatment of this chronic disease. © 2017 American Society for Bone and Mineral Research.     

Kienböck Disease in a 66-Year-Old Man after Distal Ulna Fracture

Kienböck disease after fracture-dislocations around the wrist is a rare occurrence. This case report presents a case of a 66-year-old man who developed Kienböck disease 18 months after his distal ulnar fracture. The patient developed negative ulnar variance after union of the distal ulnar fracture. Nonsurgical treatment was not effective in relieving his pain. Radial shortening osteotomy was performed based on the negative ulnar variance that developed. One year postoperatively, visual analog scale improved to 0, grip strength improved to 25 kg, and flexion-extension arc improved to 150 degrees. The patient achieved satisfactory clinical outcomes. This is a therapeutic level IV study.     

Is bladder outlet obstruction normal in elderly men without lower urinary tract symptoms?

The aim of the present study was to correlate basic voiding parameters, including uroflowmetry, symptom score, and residual urine volume with the results of pressure-flow studies applying the Abrams/Griffith nomogram, in a series of urologically asymptomatic elderly men. Twenty-nine consecutive male volunteers (median age, 66 years) without past or present urological complaints participated. Fifteen (52%) of the 29 subjectively normal men proved to have bladder outlet obstruction (BOO). Qmax <10 mL/s had a positive predictive value of 100% in diagnosing obstruction, whereas the predictive information of higher flow rates proved very modest. No significant difference existed between obstructed and unobstructed persons at any cutoff value concerning symptom score. The sensitivity as well as the positive predictive value of a residual urine volume >50 mL was zero. It is concluded that a surprisingly high prevalence of BOO in asymptomatic elderly men was demonstrated and that the correlation between pressure flow investigations and alternative diagnostic tests, i.e., flow rate, symptom score, and residual volume was weak in this group of men. It is suggested that a possible explanation for the high frequency of BOO observed in the evaluated asymptomatic men could be that the values defining obstruction have been set too low. Neurourol. Urodynam. 18:545–552, 1999. © 1999 Wiley-Liss, Inc.     

Malignant hemangiopericytoma with breast metastasis

The authors report on a rare case of malignant hemangiopericytoma. A 56-year old female patient had developed a painless node on her left gluteal region 20 years ago. Years later, the resistance became tender and was subsequently surgically removed. On histology, the lesion was identified as malignant hemangiopericytoma. After a symptom-free period of 8 years distant pulmonary metastases arose, which were removed by surgery again. Shortly afterwards the patient manifested with further metastasis involving the lung again, as well as the abdomen, the skin and the breast, leading to the patient's death 2 years later. The authors review the literature, clinical course, diagnostic possibilities, prognosis and therapeutic options of malignant hemangiopericytomas. Special attention is drawn to the unexceptionally long clinical course at this particular malignancy, as well as to the late occurrence of metastases and their unusual breast localisation.     

Comparative morphometric changes in rat cortical bone following ovariectomy and/or immobilization

Gonadal hormone deficiency following ovariectomy and skeletal unloading by limb immobilization are useful models of osteopenia. The purpose of this study was to compare changes in cortical bone after ovariectomy (OVX) or immobilization (IMM) for 6 and 12 weeks. Comparisons were also made when rats were ovariectomized or immobilized for 6 weeks and then immobilized (OVX/IMM) and ovariectomized (IMM/OVX), respectively, for 6 more weeks. Tibias and femurs were collected and static and dynamic cortical bone indices were determined by morphometric methods. Femurs from animals OVX or IMM for 12 weeks were tested for bone stiffness by torsional testing. Six and 12 weeks after OVX, there were increases in the periosteal perimeter, cortical area, and periosteal bone formation indices, indicating that ovariectomy increased modeling-dependent bone gain on the periosteal envelope, relative to controls. Contrarily, 6 and 12 weeks after IMM, there were decreases, compared with controls, in periosteal perimeter, cortical bone area, and periosteal bone formation indices. This indicates that immobilization decreased modeling-dependent bone gain on the periosteal envelope. These differences in modeling between the animals that were OVX and IMM resulted in a smaller cortical width and minimum cortical width in the IMM compared with the OVX animals. There were significant decreases in cortical bone stiffness and minimum cortical width at the fracture site following mechanical testing in the animals IMM for 12 weeks. Both ovariectomy and immobilization increased endocortical resorption surface, endocortical perimeter and expansion of the marrow cavity. Because of suppressed periosteal bone formation with increased endocortical resorption, immobilization had a greater effect on bone loss and decreased bone stiffness than did ovariectomy. In the OVX/IMM or IMM/OVX groups, there were changes that reflected both conditions. Immobilization mitigated the increase in periosteal bone formation but tended to augment endocortical resorption following ovariectomy. These results show that ovariectomy and immobilization have envelope-specific effects on rat cortical bone.     

Treatment of ovariectomized rats with the complex of rhIGF-I/IGFBP-3 Increases cortical and cancellous bone mass and improves structure in the femoral neck

Sixteen-week-old Sprague-Dawley rats were ovariectomized (Ovx) or sham-operated and housed for 8 weeks to develop osteopenia prior to systemic administration of rhIGF-I (0.9 and 2.6 mg/kg) alone or the rhIGF-I/IGFBP-3 (0.9, 2.6 and 7.5 mg/kg) complex. After 8 weeks of treatment, proximal femurs were fixed, embedded, and cut through the midneck region. Structural and dynamic histomorphometric analyses were performed using standard techniques. Ovx increased endocortical resorption and modeling-dependent periosteal formation which resulted in decreased cortical bone area. Despite increased bone formation, trabecular number, thickness, and area were all reduced due to increased resorption. Structural changes following Ovx included fewer struts and nodes, a higher percentage of the simpler strut forms, and reduced endocorticotrabecular cnnnectivity. Eight weeks of treatment with rhIGF-I or rhIGF-I/IGFBP-3 promoted periosteal and endocortical bone formation and reduced the endocortical resorption induced by Ovx. Both rhIGF-I formulations stimulated bone formation on existing trabecular surfaces which increased trabecular thickness and area but not trabecular number. These treatments prevented further deterioration of the trabecular network caused by Ovx and preserved endocortico-trabecular connectivity. In summary, changes in the femoral neck following Ovx appear to be similar in rats and humans. The highest dose of rhIGF-I/IGFBP-3 used in this study showed the best results in promoting cortical and cancellous bone formation, and appears to be promising therapy for human osteopenias.     

Cardiac electrophysiological effects of citalopram in guinea pig papillary muscle comparison with clomipramine

The effect of citalopram, a selective serotonin reuptake inhibitor (SSRI) antidepressant, was studied on cardiac action potential configuration and compared with that of the tricyclic antidepressant (TCA) clomipramine. Conventional microelectrode techniques were used in right ventricular papillary muscle preparations of the guinea pig. Citalopram caused a concentration-dependent (10-100 microM) shortening of action potential duration (APD), depression of plateau and overshoot potential, and reduction of maximum velocity of depolarization (V(max)). No significant changes in resting membrane potential were observed. Similar results were obtained with clomipramine; however, reduction of V(max) and overshoot was more pronounced with clomipramine, whereas citalopram caused relatively greater shortening of APD. Effects of both drugs were partly reversible. The results indicate that the SSRI antidepressant citalopram, similarly to TCA compounds, alters cardiac action potential configuration in guinea pig ventricular muscle, probably owing to inhibition of cardiac Na(+) and Ca(2+) channels. Differences in cardiac side effects of the two drugs may be related to their different actions on cardiac action potential configuration.     

Increased availability of angiotensin AT 1 receptors leads to sustained arterial constriction to angiotensin II in diabetes - role for Rho-kinase activation

BACKGROUND AND PURPOSE

Antagonists of angiotensin AT₁ receptors elicit beneficial vascular effects in diabetes mellitus. We hypothesized that diabetes induces sustained availability of AT₁ receptors, causing enhanced arterial constriction to angiotensin II.

EXPERIMENTAL APPROACH

To assess functional availability of AT₁ receptors, constrictions to successive applications of angiotensin II were measured in isolated skeletal muscle resistance arteries (∼150 µm) of Zucker diabetic fatty (ZDF) rats and of their controls (+/Fa), exposed acutely to high glucose concentrations (HG, 25 mM, 1 h). AT₁ receptors on cell membrane surface were measured by immunofluorescence.

KEY RESULTS

Angiotensin II-induced constrictions to first applications were greater in arteries of ZDF rats (maximum: 82 ± 3% original diameter) than in those from +/Fa rats (61 ± 5%). Constrictions to repeated angiotensin II administration were decreased in +/Fa arteries (20 ± 6%), but were maintained in ZDF arteries (67 ± 4%) and in +/Fa arteries vessels exposed to HG (65 ± 6%). In ZDF arteries and in HG-exposed +/Fa arteries, Rho-kinase activities were enhanced. The Rho-kinase inhibitor, Y27632 inhibited sustained constrictions to angiotensin II in ZDF arteries and in +/Fa arteries exposed to HG. Levels of surface AT₁ receptors on cultured vascular smooth muscle cells (VSMCs) were decreased by angiotensin II but were maintained in VSMCs exposed to HG. In VSMCs exposed to HG and treated with Y27632, angiotensin II decreased surface AT₁ receptors.

CONCLUSIONS AND IMPLICATIONS

In diabetes, elevated glucose concentrations activate Rho-kinase which inhibits internalization or facilitates recycling of AT₁ receptors, leading to increased functional availability of AT₁ receptors and sustained angiotensin II-induced arterial constriction.     

Bone-specific alkaline phosphatase activity in dairy cows

Bone-specific alkaline phosphatase is considered the single most accurate marker of bone formation. In this study, 75 healthy Holstein dairy cows in their first, second, third, fourth or fifth parities underwent serum bone-specific alkaline phosphatase quantification. The results indicate that enzyme activity values have a decreasing pattern with increasing order of parity (p < 0.05). However, the differences between cows in second and third parity and also between cows in fourth and fifth parity were not statistically significant (p > 0.1). We concluded that bone-specific alkaline phosphatase measurement by heat inactivation provides a simple method to determine bone metabolic status and useful data to evaluate calcium availability in dairy cows.