The Effects of NPY1 Receptor Antagonism on Intervertebral Disc and Bone Changes in Ovariectomized Rats.

STUDY DESIGN: Basic science. OBJECTIVE: To compare the effects of a neuropeptide Y1 receptor antagonist (NPY-1RA) to estrogen on maintaining vertebral bone microarchitecture and disc height in a rat model of menopause. METHODS: This study was an institutional animal care approved randomized control study with 104 ovariectomized rats and 32 intact control animals. Comparison of disc height, trabecular bone, body weights, circulating levels of NPY and estrogen, and distribution of Y1 receptors in the intervertebral disc in an established rodent osteoporotic model were made at baseline and after 2, 4, and 8 weeks after receiving either an implant containing estrogen or an antagonist to the neuropeptide Y1 receptor. Data was compared statistically using One-way analysis of variance. RESULTS: Circulating levels of estrogen increased and NPY decreased following estrogen replacement, with values comparable to ovary-intact animals. NPY-1RA-treated animals had low estrogen and high NPY circulating levels and were similar to ovariectomized control rats. Both NPY-1RA and estrogen administration were able reduce, menopause associated weight gain. NPY-1RA appeared to restore bone formation and maintain disc height, while estrogen replacement prevented further bone loss. CONCLUSION: NPY-1RA in osteoporotic rats activates osteoblast production of bone and decreased marrow and body fat more effectively than estrogen replacement when delivered in similar concentrations. Annulus cells had NPY receptors, which may play a role in disc nutrition, extracellular matrix production, and pain signaling cascades.

Tracking tidal volume noninvasively in volunteers using a tightly controlled temperature-based device: A proof of concept paper.

INTRODUCTION: There is a paucity of noninvasive respiratory monitors for patients outside of critical care settings. The Linshom respiratory monitoring device is a novel temperature-based respiratory monitor that measures the respiratory rate as accurately as capnography. OBJECTIVES: Determine whether the amplitude of the Linshom temperature profile was an accurate, surrogate and qualitative metric of the tidal volume (VT ) that tracks VT in healthy volunteers. METHODS: Forty volunteers breathed room air spontaneously through a tight-fitting continuous positive airway pressure mask with a Linshom device mounted in the mask. VT was measured contemporaneously using a standalone Maquet Servo-i ICU ventilator. The amplitudes of the Linshom temperature profiles were paired with the contemporaneous VT measurements using least squares linear regression analysis and the coefficient of variation (R2 ) was determined. RESULTS: Forty volunteers completed the study. The data from 30 of the volunteers were analysed and are presented; data from 10 volunteers were not included due to protocol violations and/or technical issues unrelated to Linshom. The fluctuations in the amplitude of the Linshom temperature profiles mapped closely with the measured VT using least squares linear regression analyses yielding a mean R2 (95% CI) value of 0.87 (0.84-0.90). CONCLUSION: These results support the notion that the Linshom temperature profile is an accurate and reliable surrogate that tracks changes in VT in healthy volunteers. Further studies are warranted in patients in clinical settings to establish the effectiveness of this monitor.

Sustained Release of Demineralized Bone Matrix Protein in Osteoporotic Rats.

Demineralized bone matrix protein (DBM) was considered highly effective in stimulating bone healing. The objective of the study was to explore the use of tricalcium phosphate (TCP) delivery system to continuously deliver DBM in an osteoporotic condition and to evaluate changes in bone density and preservation of the spine. Ovariectomized Sprague Dawley rats were divided into three equal groups (n=16 per group). Animals in group I served as control, animals in groups II and III were surgically implanted with either empty (SHAM) or DBM filled TCP implants adjacent to L4/L5. Eight animals from each group were euthanized at 2 and 8 weeks post implantation. Femurs were evaluated for changes in density, and the lumbar spine was evaluated for changes in the endplate. Results of this study revealed (1) TCP implants were capable of delivering DBM for long duration, (2) use of sustained delivery of DBM did not induce untoward effects in the vital organs or in the uterus, fallopian tubes, or vaginal tissues, (3) DBM had no effect on chondrocyte differentiation in the spine, and (4) DBM did not increase bone density in osteoporotic female rats.

The Effect Of Selective Serotonin Reuptake Inhibitors and Antidiabetic Drugs on Cardiomyocytes.

Recent reports in the literature show an increase in the risk of heart related events in patients treated with tricyclic antidepressants. There is also evidence that serotonin reuptake inhibitors (SSRIs) are negatively associated with heart failure. The objective of our study is to determine if cardiomyocytes in culture can be used as a tool to mimic clinical scenarios and to evaluate therapeutic concentrations of SSRIs (fluoxetine) and antidiabetic (troglitazone) medication. Cardiomyocytes were grown in a tissue culture environment and challenged with therapeutic concentrations of SSRIs alone or a combination of SSRIs and antidiabetic drugs. Intracellular markers for stress and cytomorphometric analysis indicated SSRIs and SSRIs in combination with antidiabetic drugs negatively impact the health of the cardiomyocytes with time in culture. Analysis of the nuclear area and cytoplasmic changes are sensitive enough to use a cell-based model for determination of adverse effects associated with co-administration of drugs.