Clinical and biochemical response to neridronate treatment in a patient with osteoporosis-pseudoglioma syndrome (OPPG)

Osteoporosis-pseudoglioma syndrome (OPPG) is a rare autosomal recessive syndrome characterized by juvenile-onset osteoporosis and ocular abnormalities due to a low-density lipoprotein receptor-related protein 5 (LRP5) gene mutation. Treatment with bisphosphonates, particularly with pamidronate and risedronate, has been reported to be of some efficacy in this condition. We report on a patient with OPPG due to an LRP5 gene mutation, who showed an encouraging response after a 36-month period of neridronate therapy. We report a case of a patient treated with bisphosphonates. Bisphosphonates should be administered in OPPG patients as a first-line therapy during early childhood

Serum creatine kinase isoenzymes in children with osteogenesis imperfecta

This study evaluates serum creatine kinase isoenzyme activity in children with osteogenesis imperfecta to determine its usefulness as a biochemical marker during treatment with bisphosphonate. The changes of creatine kinase (CK) isoenzyme activity during and after discontinuation therapy were observed. These results could be useful in addressing over-treatment risk prevention. Introduction The brain isoenzyme of creatine kinase (CKbb) is highly expressed in mature osteoclasts during osteoclastogenesis, thus plays an important role in bone resorption. We previously identified high serum CKbb levels in 18 children with osteogenesis imperfect (OI) type 1 treated for 1 year with bisphosphonate (neridronate). In the present study, serum CK isoenzymes were evaluated in the same children with continuous versus discontinued neridronate treatment over a further 2-year follow-up period. Methods This study included 18 children with OI type 1, 12 with continued (group A) and 6 with ceased (group B) neridronate treatment. Auxological data, serum biochemical markers of bone metabolism, bone mineral density z-score, and serum total CK and isoenzyme activities were determined in both groups. Results Serum CKbb was progressively and significantly increased in group A (p < 0.004) but rapidly decreased to undetectable levels in group B. In both groups, the cardiac muscle creatine kinase isoenzyme (CKmb) showed a marked decrease, while serum C-terminal telopeptide (CTx) levels were almost unchanged. Conclusions This study provides evidence of the cumulative effect of neridronate administration in increasing serum CKbb levels and the reversible effect after its discontinuation. This approach could be employed for verifying the usefulness of serum CKbb as a biochemical marker in patients receiving prolonged bisphosphonate treatment. Moreover, the decreased serum CKmb levels suggest a systemic effect of these drugs

Onset of thermal convection in a horizontal porous layer saturated by a power-law fluid

A horizontal porous layer saturated by a non-Newtonian fluid is taken into account. The fluid is a Ostwald-De Waele type of fluid. The layer is heated from below while the upper boundary is isothermal. The lower boundary is impermeable and the upper one is free. A fully developed basic throughflow is considered. The basic state is perturbed by employing small amplitude perturbations such that a linear stability analysis is performed. The disturbances are assumed to be normal modes and a system of ordinary differential equations governing the perturbation dynamics is obtained. These ODEs form an eigenvalue problem that is solved numerically: both the neutral stability curves and the threshold values for the onset of convection are presented

Charge redistribution in the formation of one-dimensional lithium wires on Cu(001)

We describe the formation of one-dimensional lithium wires on a Cu(001) substrate, providing an atomic-scale description of the onset of metallization in this prototypical adsorption system. A combination of helium atom scattering and density-functional theory reveals pronounced changes in the electronic charge distribution on the formation of the c(5√2×√2)R45° Li/Cu(001) structure, as in-plane bonds are created. Charge donation from Li-substrate bonds is found to facilitate the formation of stable, bonded, and depolarized chains of Li adatoms that coexist with an interleaved phase of independent adatoms. The resultant overlayer has a commensurate charge distribution and lattice modulations but differs fundamentally from structurally similar charge-density wave systems

Humoral and cellular immunopathology of hepatic and cardiac hamster-into-rat xenograft rejection: Marked stimulation of IgM^++bright/IgD^+dull splenic B cells

Normal Lewis rat serum contains antibodies (IgM > IgG) that bind to hamster leukocytes and endothelial cells. Transplantation of either the heart or liver from hamster rat results in release of hamster hematolymphoid cells from the graft, which lodge in the recipient spleen (cell migration), where recipient T- and B-cell populations initiate DNA synthesis within one day. There is marked stimulation of splenic IgM++(bright)/IgD+(dull) B cells in the marginal zone and red pulp, which account for 48% of the total splenic blast cell population by 4 days after liver transplantation. CD4+ predominant T-cell proliferation in the splenic periarterial lymphatic sheath and paracortex of peripheral lymph nodes occurs almost simultaneously. The effector phase of rejection in cardiac recipients is dominated by complement-fixing IgM antibodies, which increase daily and result in graft destruction in 3 to 4 days, even in animals treated with FK506. In liver recipients, combined antibody and cellular rejection, associated with graft infiltration by OX8+ natural killer, and fewer W3/25+ (CD4) lymphocytes, are responsible for graft failure in untreated recipients at 6 to 7 days. FK506 inhibits the T-cell response in liver recipients and significantly prolongs graft survival, but does not prevent the rise or deposition of IgM antibodies in the graft. However, a single injection of cyclophosphamide 10 days before transplantation effectively depletes the splenic IgM++(bright)/IgD+(dull) cells and in combination with FK506, results in 100% survival of both cardiac and hepatic xenografts for more than 60 days. Although extrapolation of morphological findings to functional significance is fraught with potential problems, we propose the following mechanisms of xenograft rejection. The reaction initially appears to involve primitive host defense mechanisms, including an IgM-producing subpopulation of splenic B cells and natural killer cells. Based on the reaction and distribution of OX8+ and W3/25+ cells, antibody dependent cell cytotoxicity and delayed-type hypersensitivity responses seem worthy of further investigation as possible effector mechanisms. Effective control of xenograft rejection is likely to require a dual pharmaceutical approach, one to contain T-cell immunity and another to blunt the primitive B-cell response

Stability of a buoyant Oldroyd-B flow saturating a vertical porous layer with open boundaries

The performance of several engineering applications are strictly connected to the rheology of the working fluids and the Oldroyd-B model is widely employed to describe a linear viscoelastic behaviour. In the present paper, a buoyant Oldroyd-B flow in a vertical porous layer with permeable and isothermal boundaries is investigated. Seepage flow is modelled through an extended version of Darcy’s law which accounts for the Oldroyd-B rheology. The basic stationary flow is parallel to the vertical axis and describes a single-cell pattern where the cell has an infinite height. A linear stability analysis of such a basic flow is carried out to determine the onset conditions for a multicellular pattern. This analysis is performed numerically by employing the shooting method. The neutral stability curves and the values of the critical Rayleigh number are evaluated for different retardation time and relaxation time characteristics of the fluid. The study highlights the extent to which the viscoelasticity has a destabilising effect on the buoyant flow. For the limiting case of a Newtonian fluid, the known results available in the literature are recovered, namely a critical value of the Darcy–Rayleigh number equal to 197.081 and a corresponding critical wavenumber of 1.05950

On the stability of parallel flow in a vertical porous layer with annular cross-section

The linear stability of buoyant parallel flow in a vertical porous layer with an annular cross-section is investigated. The vertical cylindrical boundaries are kept at different uniform temperatures and they are assumed to be impermeable. The emergence of linear instability by convection cells is excluded on the basis of a numerical solution of the linearised governing equations. This result extends to the annular geometry the well-known Gill's theorem regarding the impossibility of convective instability in a vertical porous plane slab whose boundaries are impermeable and isothermal with different temperatures. The extension of Gill's theorem to the annular domain is approached numerically by evaluating the growth rate of normal mode perturbations and showing that its sign is negative, which means asymptotic stability of the basic flow. A concurring argument supporting the absence of linear instability arises from the investigation of cases where the impermeability condition at the vertical boundaries is relaxed and a partial permeability is modelled through Robin boundary conditions for the pressure. With partially permeable boundaries, an instability emerges which takes the form of axisymmetric normal modes.Comment: 12 pages, 5 figure

Viscous heating and instability of the adiabatic buoyant flows in a horizontal channel

The stability of buoyant flows occurring in the mixed convection regime for a viscous fluid in a horizontal plane-parallel channel with adiabatic walls is investigated. The basic flow features a parallel velocity field under stationary state conditions. There exists a duality of flows, for every prescribed value of the mass flow rate across the channel cross-section, caused by the combined actions of viscous dissipation and the buoyancy force. As pointed out in a previous study, only the primary branch of the dual solutions is compatible with the Oberbeck-Boussinesq approximation. Thus, the stability analysis will be focused on the stability of such flows. The onset of the thermal instability with small-amplitude perturbations of the basic flow is investigated by assuming a very large Prandtl number, which is equivalent to a creeping flow regime. The neutral stability curves and the critical parametric conditions for the onset of instability are determined numerically

Viscous heating and instability of the adiabatic buoyant flows in a horizontal channel

The stability of buoyant flows occurring in the mixed convection regime for a viscous fluid in a horizontal plane-parallel channel with adiabatic walls is investigated. The basic flow features a parallel velocity field under stationary state conditions. There exists a duality of flows, for every prescribed value of the mass flow rate across the channel cross-section, caused by the combined actions of viscous dissipation and of the buoyancy force. As pointed out in a previous study, only the primary branch of the dual solutions is compatible with the Oberbeck-Boussinesq approximation. Thus, the stability analysis will be focussed on the stability of such flows. The onset of the thermal instability with small-amplitude perturbations of the basic flow is investigated by assuming a very large Prandtl number, which is equivalent to a creeping flow regime. The neutral stability curves and the critical parametric conditions for the onset of instability are determined numerically