Uroflowmetric analysis and derivation of nomograms for normal paediatric Indian population between 5 to 15 years of age.

Objective: We aimed to established normal uroflowmetric values and subsequently derived nomograms of maximum flow rate (Qmax) and average flow rate (Qavg) against voided volume (VV) in children aged 5-15 years at our institute. Methods: A total of 440 children underwent uroflowmetric evaluation with no history of urological, renal, psychiatric, or neurological disorder between 5 and 15 years of age. Each subject data regarding Qmax, Qavg, VV, time to Qmax, and flow time, as well as age, sex, height, and weight were recorded. Of the 440 children, around 300 (68.18%) children could produce a normal flow rate at VV of more than 50 mL. Of the remaining 140 (31.82%) children, 50.00% voided less than 50 mL, and remaining 50.00% had abnormal voiding pattern, staccato or interrupted (21.43% each) and plateau or tower shaped (3.57% each). Cases were divided into two age groups (5-9 years and 10-15 years), and uroflowmetric analysis was done between boys and girls in both age groups to derive nomograms of Qavg and Qmax. Results: Qmax and Qavg flow nomograms were plotted for boys and girls. Mean Qmax for boys was 16.68 mL/s and for girls 20.69 mL/s. The mean Qavg values were 11.04 mL/s and 8.60 mL/s for girls and boys, respectively. The Qmax and Qavg values were higher in girls. There were significant increases in flow rates with increasing age, body surface area, and VV in both sexes. Conclusions: Nomograms for Qmax and Qavg may be a useful tool in evaluation of lower urinary tract disturbances in children.

Good, Bad, or Ugly: the Biological Roles of Bone Marrow Fat.

PURPOSE OF REVIEW: Bone marrow fat expresses mixed characteristics, which could correspond to white, brown, and beige types of fat. Marrow fat could act as either energy storing and adipokine secreting white fat or as a source of energy for hematopoiesis and bone metabolism, thus acting as brown fat. However, there is also a negative interaction between marrow fat and other elements of the bone marrow milieu, which is known as lipotoxicity. In this review, we will describe the good and bad roles of marrow fat in the bone, while focusing on the specific components of the negative effect of marrow fat on bone metabolism. RECENT FINDINGS: Lipotoxicity in the bone is exerted by bone marrow fat through the secretion of adipokines and free fatty acids (FFA) (predominantly palmitate). High levels of FFA found in the bone marrow of aged and osteoporotic bone are associated with decreased osteoblastogenesis and bone formation, decreased hematopoiesis, and increased osteoclastogenesis. In addition, FFA such as palmitate and stearate induce apoptosis and dysfunctional autophagy in the osteoblasts, thus affecting their differentiation and function. Regulation of marrow fat could become a therapeutic target for osteoporosis. Inhibition of the synthesis of FFA by marrow fat could facilitate osteoblastogenesis and bone formation while affecting osteoclastogenesis. However, further studies testing this hypothesis are still required.

Lamin A expression in circulating osteoprogenitors as a potential biomarker for frailty: The Nepean Osteoporosis and Frailty (NOF) Study.

Lamin A is a protein of the nuclear lamina. Low levels of lamin A expression are associated with osteosarcopenia in mice. In this study, we hypothesized that low lamin A expression is also associated with frailty in humans. We aimed to develop a non-invasive method to quantify lamin A expression in epithelial and circulating osteoprogenitor (COP) cells, and to determine the relationship between lamin A expression and frailty in older individuals. COP cells and buccal swabs were obtained from 66 subjects (median age 74; 60% female; 26 non-frail, 23 pre-frail, and 17 frail) participating at the Nepean Osteoporosis and Frailty (NOF) Study. We quantified physical performance and disability, and stratified frailty in this population. Lamin A expression in epithelial and COP cells was quantified by flow cytometry. Linear regression models estimated the relationship between lamin A expression in buccal and COP cells, and prevalent disability and frailty. Lamin A expression in buccal cells showed no association with either disability or frailty. Low lamin A expression values in COP cells were associated with frailty. Frail individuals showed 60% lower levels of lamin A compared to non-frail (95% CI -36 to -74%, p<0.001) and 62% lower levels compared to pre-frail (95%CI -40 to -76%, p<0.001). In summary, we have identified lamin A expression in COP cells as a strong indicator of frailty. Further work is needed to understand lamin A expression as a risk stratifier, biomarker, or therapeutic target in frail older persons.

Age, gender, and percentage of circulating osteoprogenitor (COP) cells: The COP Study.

Circulating osteoprogenitor (COP) cells are blood-borne cells which express a variety of osteoblastic markers and are able to form bone nodules in vivo. Whereas a high percentage of COP cells (%COP) is associated with vascular calcification, low %COP has been associated with disability and frailty. However, the reference range of %COP in age- and gender-matching populations, and the age-related changes in %COP remain unknown. A cross-sectional study was undertaken in 144 healthy volunteers in Western Sydney (20-90year-old, 10 male and 10 female subjects per decade). %COP was quantified by flow cytometry. A high inter-and intra-rater reliability was found. In average, in this healthy population average of %COP was 0.42. There was no significant difference in %COP among the age groups. Similarly, no significant difference was found in %COP with gender, weight, height or BMI. In addition, we identified a normal reference range of %COP of 0.1-3.8%. In conclusion, in addition to the identification of steady levels of COP cells with age, we also identified a normal reference range of %COP, which could be used in future studies looking at musculoskeletal diseases in older populations.

Aging alters bone-fat reciprocity by shifting in vivo mesenchymal precursor cell fate towards an adipogenic lineage.

Bone marrow derived mesenchymal progenitor cells (MPCs) play an important role in bone homeostasis. Age-related changes occur in bone resulting in a decrease in bone density and a relative increase in adipocity. Although in vitro studies suggest the existence of an age-related lineage switch between osteogenic and adipogenic fates, stem cell and microenvironmental contributions to this process have not been elucidated in vivo. In order to study the effects of MPC and microenvironmental aging on functional engraftment and lineage switching, transplantation studies were performed under non-myeloablative conditions in old recipients, with donor MPCs derived from young and old green fluorescent protein (GFP) transgenic mice. Robust engraftment by young MPCs or their progeny was observed in the marrow, bone-lining region and in the matrix of young recipients; however, significantly lower engraftment was seen at the same sites in old recipients transplanted with old MPCs. Differentiation of transplanted MPCs strongly favored adipogenesis over osteogenesis in old recipients irrespective of MPC donor age, suggesting that microenvironmental alterations that occur with in vivo aging are predominately responsible for MPC lineage switching. These data indicate that aging alters bone-fat reciprocity and differentiation of mesenchymal progenitors towards an adipogenic fate.

Long-term functional engraftment of mesenchymal progenitor cells in a mouse model of accelerated aging.

Age-related osteoporosis is characterized by a decrease in bone-forming capacity mediated by defects in the number and function of osteoblasts. An important cellular mechanism that may in part explain osteoblast dysfunction that occurs with aging is senescence of mesenchymal progenitor cells (MPCs). In the telomere-based Wrn(-/-) Terc(-/-) model of accelerated aging, the osteoporotic phenotype of these mice is also associated with a major decline in MPC differentiation into osteoblasts. To investigate the role of MPC aging as a cell-autonomous mechanism in senile bone loss, transplantation of young wild-type whole bone marrow into Wrn(-/-) Terc(-/-) mutants was performed and the ability of engrafted cells to differentiate into cells of the osteoblast lineage was assessed. We found that whole bone marrow transplantation in Wrn(-/-) Terc(-/-) mice resulted in functional engraftment of MPCs up to 42 weeks, which was accompanied by a survival advantage as well as delays in microarchitectural features of skeletal aging.

Utility of repetitive transcranial magnetic stimulation as an augmenting treatment method in treatment-resistant depression.

BACKGROUND: About 30-46% of patients with major depressive disorder (MDD) fail to fully respond to initial antidepressants. Treatment-resistant depression is a severely disabling disorder with no proven treatment options; novel treatment methods, such as repetitive transcranial magnetic stimulation (rTMS) can be used as augmentation to ongoing pharmacotherapy or as a solitary method of treatment. AIM: To evaluate the utility of rTMS as an augmenting method in treatment-resistant depression. MATERIALS AND METHODS: In an open-label study, 21 patients with DSM-IV MDD without psychotic features who had failed to respond to an adequate trial of at least 2 antidepressants were given rTMS therapy for 4 weeks keeping the dose of pre-existing antidepressants unchanged. High-frequency (10 Hz) stimulations were delivered over left dorsolateral prefrontal cortex at an intensity of 110% of the patient's motor threshold. Treatment response was defined as a reduction in score on the Hamilton Rating Scale for Depression (HAM-D) from baseline to end of treatment. Secondary efficacy measures included scores on the Clinical Global Impressions-Change and -Severity scales. RESULTS: At the end of 4 weeks, 19 patients completed the 4 weeks study and were assessed. In ITT analysis the mean HAM-D17 scores were reduced from 30.80±5.00 to 19.00±6.37 (t=8.27, P<0.001). Only 4 patients reported headache but there was no discontinuation due to adverse effects. CONCLUSIONS: The study indicates the potential utility of rTMS as an augmenting agent in treatment-resistant depression. Adequately powered, randomized controlled trials are necessary to evaluate the role of rTMS in treatment-resistant depression.

Effect of Tinospora cordifolia on gamma ray-induced perturbations in macrophages and splenocytes.

Tinospora cordifolia (RTc) has already been reported to protect whole-body lethally irradiated mice. This study has focussed on certain aspects of immuno-competence, which are adversely affected by irradiation. This study included estimation of spleen size, cell count, DNA fragmentation and apoptosis in splenocytes. The adherence, spreading and phagocytic activities of macrophages were also assessed. Cytokines in serum and anti-oxidants in plasma were also estimated. Administration of RTc (200 mg/kg.b.wt.) one hour before irradiation showed recovery of spleen weight from 49% of control in irradiated group to 93%; apoptosis from 19% to 2.8%; DNA fragmentation from 43% to 20.4%; macrophage adherence form 75% of control to 120% and macrophage spread size from 8 microm to 15 microm. RTc also stimulated proliferation in splenocytes in a dose-dependent manner. RTc administration before irradiation also increased levels of IL-1beta and GM-CSF levels, from 56 pg/ml and 53 pg/ml respectively in irradiated group to 59 pg/ml and 63 pg/ml. Similarly, radiation-induced decrease of anti-oxidant potential of plasma (32 Fe(2+) equiv.) as compared to control (132 Fe(2+) equiv.) was countered by administration of RTc before irradiation (74.2 Fe(2+) equiv.) RTc treatment thus reveals several radio-protective mechanisms.

Synthesis, Biological, Spectral, and Thermal Investigations of Cobalt(II) and Nickel(II) Complexes of N-Isonicotinamido -2',4'-Dichlorobenzalaldimine.

A new series of 12 complexes of cobalt(II) and nickel(II) with N-isonicotinamido-2',4'-dichlorobenzalaldimine (INH-DCB) with the general composition MX(2) . n(INH-DCB) [M = Co(II) or Ni(II), X = Cl(-) ,Br(-), NO(3) (-), NCS(-), or CH(3)COO(-), n = 2; X = ClO(4) (-), n = 3] have been synthesized. The nature of bonding and the stereochemistry of the complexes have been deduced from elemental analyses, infrared, electronic spectra, magnetic susceptibility, and conductivity measurements. An octahedral geometry has been suggested for all the complexes. The metal complexes were screened for their antifungal and antibacterial activities on different species of pathogenic fungi and bacteria and their biopotency has been discussed.

Synthesis, Spectral, and Biological Properties of Copper(II) Complexes of Thiosemicarbazones of Schiff Bases Derived from 4-Aminoantipyrine and Aromatic Aldehydes.

We have synthesized a novel series of Schiff bases by condensation of 4-aminoantipyrine and various aromatic aldehydes followed by reaction with thiosemicarbazide. These thiosemicarbazones are potential ligands toward transition metal ions. The reaction of copper(II) salts with 4[N-(benzalidene)amino]antipyrinethiosemicarbazone (BAAPTS), 4[N-(4'-methoxybenzalidene) amino] antipyrinethiosemicarbozone (MBAAPTS), 4[N-(4'-dimethylamino benzalidene) amino] antipyrinethiosemicarbazone (DABAAPTS), and 4[N-(cinnamalidene) amino] antipyrinethiosemicarbazone (CAAPTS) resulted in the formation of solid complexes with the general composition CuX(2) . (H(2)O)(L)(X = Cl, Br,NO(3),NCS, or CH(3)COO; L = BAAPTS, MBAAPTS, DABAAPTS, or CAAPTS). These complexes were characterized through elemental analysis, molecular weight, electrical conductance, infrared, electronic spectra, and magnetic susceptibilities at room temperature. Copper(II) complexes with BAAPTS and MBAAPTS were screened for antibacterial and antifungal properties and have exhibited potential activity. Thermal stabilities of two representative complexes were also investigated.