Vitamin C Prevents Hypogonadal Bone Loss

Epidemiologic studies correlate low vitamin C intake with bone loss. The genetic deletion of enzymes involved in de novo vitamin C synthesis in mice, likewise, causes severe osteoporosis. However, very few studies have evaluated a protective role of this dietary supplement on the skeleton. Here, we show that the ingestion of vitamin C prevents the low-turnover bone loss following ovariectomy in mice. We show that this prevention in areal bone mineral density and micro-CT parameters results from the stimulation of bone formation, demonstrable in vivo by histomorphometry, bone marker measurements, and quantitative PCR. Notably, the reductions in the bone formation rate, plasma osteocalcin levels, and ex vivo osteoblast gene expression 8 weeks post-ovariectomy are all returned to levels of sham-operated controls. The study establishes vitamin C as a skeletal anabolic agent. © 2012 Zhu et al

Vitamin C Prevents Hypogonadal Bone Loss

Abstract Epidemiologic studies correlate low vitamin C intake with bone loss. The genetic deletion of enzymes involved in de novo vitamin C synthesis in mice, likewise, causes severe osteoporosis. However, very few studies have evaluated a protective role of this dietary supplement on the skeleton. Here, we show that the ingestion of vitamin C prevents the low-turnover bone loss following ovariectomy in mice. We show that this prevention in areal bone mineral density and micro-CT parameters results from the stimulation of bone formation, demonstrable in vivo by histomorphometry, bone marker measurements, and quantitative PCR. Notably, the reductions in the bone formation rate, plasma osteocalcin levels, and ex vivo osteoblast gene expression 8 weeks post-ovariectomy are all returned to levels of sham-operated controls. The study establishes vitamin C as a skeletal anabolic agent

MC3T3 infiltration and proliferation in bovine trabecular scaffold regulated by dynamic flow bioreactor and augmented by low-intensity pulsed ultrasound

Background: Low-intensity pulsed ultrasound (LIPUS) has been used in both basic research and clinical settings for its therapeutic potential in promoting tissue healing. Clinical data has shown that LIPUS can accelerate fresh fracture healing. However, the treatment for aging osteoporosis and non-union is still unclear. In addition, the mechanism of ultrasound promoted bone healing has remained unknown. Objective: It is proposed that noninvasive ultrasound treatment can enhance local fluid flow within the tissue to initiate remodeling and regeneration. The goal of this study was to evaluate the effects of dynamic ultrasound in promoting cellular mechanotransduction within bioengineered organic scaffolds to trigger osteogenesis and mineralization. Methods: The experiment was designed in two-fold: to evaluate the role of LIPUS on osteoblastic-like (MC3T3) cell proliferation and mineralization in response to acoustic waves, using biomechanical rate-dependent signals in a bioreactor; and, to evaluate the new scaffold experimentation techniques, in order to generate a potential implantable biomaterial for orthopedic tissue regeneration and repair. Results: LIPUS treatment on MC3T3 cells yielded enhanced cellular mineralization (**p < 0.001) in 3-D scaffolding, but reduced the total cell numbers (*p < 0.05), using Alizarin Red staining and cell counting analyses, respectively, in comparison to the control. Conclusion: This study suggests that LIPUS, if applied at proper frequency and duty cycle, can promote cell mineralization within the 3-D organic scaffold under in vitro setting. The translational component of this experiment seeks to draw a parallel to the potential pre-treatment of scaffolds for implantation before orthopedic surgery, which could prove to greatly benefit the patient in accelerating fracture healing and tissue regeneration. The Translational Potential of this Article: LIPUS stimulation was critical in contributing to the mechanical signaling transductions that activated bone enhancement parameters in MC3T3 cells regulated by bioreactor, and thus has potential to change how we pretreat scaffolds for orthopedic surgery and noninvasively accelerate healing in the future, e.g., in an extreme condition such as long-term space mission. Keywords: Bioreactor, Bone tissue engineering and regeneration, Low-intensity pulsed ultrasound, Scaffol

Acute Encephalitis in an Adult with Diffuse Large B-Cell Lymphoma with Secondary Involvement of the Central Nervous System: Infectious or Non-Infectious Etiology?

Both infectious and non-infectious etiologies of acute encephalitis have been described, as well as their specific presentations, diagnostic tests, and therapies. Classic findings of acute encephalitis include altered mental status, fever, and new lesions on neuroimaging or electroencephalogram (EEG). We report an interesting case of a 61-year-old male with a history of diffuse large B-cell lymphoma with secondary involvement of the central nervous system (SCNS-DLBCL). He presented with acute encephalitis: altered mental status, fever, leukocytosis, neuropsychiatric symptoms, multiple unchanged brain lesions on computed tomography scan of the head, and EEG showed mild to moderate diffuse slowing with low-moderate polymorphic delta and theta activity. With such a wide range of symptoms, the differential diagnosis included paraneoplastic and autoimmune encephalitis. Infectious and autoimmune/paraneoplastic encephalitis in patients with SCNS-DLBCL are not well documented in the literature, hence diagnosis and therapy becomes challenging. This case report describes the patient’s unique presentation of acute encephalitis

Oral Vitamin C Stimulates the Expression of Osteoblast Differentiation Genes.

<p>Quantitative PCR (qPCR) on RNA isolated from bone marrow stromal cells harvested from mice that were fed with vitamin C (5 mg/day, VC) following ovariectomy (OVX) or sham operation (Sham). The cells were cultured in ascorbate-free medium for 6 or 10 days following which the expression of several osteoblast differentiation genes and transcription factors, namely <i>bone sialoprotein</i> (<i>BSP</i>), <i>bone morphogenetic protein-2</i> (<i>BMP2</i>), <i>Runx2</i>, <i>osterix</i>, and <i>alkaline phosphatase</i> (<i>ALP</i>) were quantitated. Statistics: mean±SEM; comparisons between vitamin C-treated and untreated groups (*p<0.05, **p<0.01); qPCR in triplicate; n = 5 mice per group (pooled).</p

Oral Vitamin C Stimulates Bone Formation in Ovariectomized Mice.

<p>Representative reverse phase contrast (showing trabecular structure) (A) and fluorescence micrographs (showing calcein labels) (B) 8 weeks following ovariectomy (OVX) or sham operation (C) in 6 month-old mice. The mice were allowed to ingest vitamin C (VC) (5 mg/day) in drinking water <i>ad libitum</i>. Measurements of dynamic parameters, including mineralizing surface (MS) (C), mineral apposition rate (MAR) (D), bone formation rate (BFR) (E) and tartrate-resistant acid phosphatase- (TRAP-) labeled surfaces (Resorbed S./BPm) (F). Markers of bone turnover measured in plasma, namely osteocalcin (formation) (G) and C-telopeptide (resorption) (H). Statistics: comparisons were made for differences between ovariectomized and sham-operated mice (*p<0.05, **p<0.01), and within the sham-operated and ovariectomized groups, between vitamin C treated and controls (∧p<0.05, ∧∧p<0.01); n = 5 mice per group.</p

Oral Vitamin C Prevents Structural Deterioration in Ovariectomized Mice.

<p>Measurements by micro-CT (Scanco μCT40) of static parameters, including bone mineral density (volumetric) (A), bone volume fraction (BV/TV) (B), trabecular number (TbN) (C), trabecular thickness (TbTh) (D), trabecular spacing (TbS) (E), and bone volume (BV) (F), measured 8 weeks following ovariectomy (OVX) or sham operation (C) in 6 month-old mice. The mice were allowed to ingest vitamin C (VC) (5 mg/day) in drinking water <i>ad libitum</i>. Panel G shows representative μ-CT images from the respective groups. Statistics: comparisons were made for differences between ovariectomized and sham-operated mice (*p<0.05, **p<0.01), and within the sham-operated and ovariectomized groups, between vitamin C treated and controls (∧p<0.05, ∧∧p<0.01); n = 5 mice per group.</p