Enhanced Bone Regeneration Using Porcine Small Intestinal Submucosa

Small instestinal submucosa (SIS) is an easily produced material that has been used experimentally for tissue engineering. To evaluate the ability of SIS to facilitate bone growth within a long-bone defect, a segment of the radius was surgically removed in adult, female Sprague-Dawley rats. The defect was either left unfilled or implanted with SIS, demineralized cortical bone (DMCB), or ovalbumin. The defect was evaluated radiographically and histologically after 3, 6, 12, and 24 weeks. Tissue remodeling within the defect was evident by week 3 in SIS- and DMCB-treated rats. Filling was characterized initially by infiltration of mononuclear cells and extracellular material in SIS-implanted rats and multifocal remodeling bone particles and cartilage formation in DMCB implanted rats. Cartilage was observed as early as 3 weeks and bone as early as 6 weeks in SIS-implanted rats. Filling of the defect arose from multiple foci in DMCB-implanted rats, but was contiguous with and parallel to the ulnar shaft in SIS-implanted rats, suggesting that defect repair by SIS may be conductive rather than inductive. Rats in which the defect was left unfilled demonstrated slow but progressive filling of the defect, characterized by mononuclear cell infiltrates and fibrous extracellular material. In summary, SIS facilitated rapid filling of a longbone defect. These results suggest that SIS may be useful as a bone repair material.     

Viscosupplementation with hyaluronic acid in the treatment for cartilage lesions: a review of current evidence and future directions

Diseases involving the articular cartilage are one of the leading causes of physical impairment among the adult population. While surgical technique and advancement have allowed us effective means at treating these diseases, this is not without significant risk and morbidity. With a very solid safety profile, viscosupplementation with hyaluronic acid (HA) derivatives has become an excellent modality for treating diseased articular cartilage. Recent literature supports the use of HA not only in the management of the pain associated with osteoarthritis but also as a disease-modifying agent as well. Further studies have started to define exciting new roles for viscosupplementation in the treatment for acute injuries to the joint microenvironment.     

Alterations in the motor neuron–renshaw cell circuit in the Sod1G93A mouse model

Motor neurons become hyperexcitable during progression of amyotrophic lateral sclerosis (ALS). This abnormal firing behavior has been explained by changes in their membrane properties, but more recently it has been suggested that changes in premotor circuits may also contribute to this abnormal activity. The specific circuits that may be altered during development of ALS have not been investigated. Here we examined the Renshaw cell recurrent circuit that exerts inhibitory feedback control on motor neuron firing. Using two markers for Renshaw cells (calbindin and cholinergic nicotinic receptor subunit alpha2 [Chrna2]), two general markers for motor neurons (NeuN and vesicular acethylcholine transporter [VAChT]), and two markers for fast motor neurons (Chondrolectin and calcitonin‐related polypeptide alpha [Calca]), we analyzed the survival and connectivity of these cells during disease progression in the Sod1^G93A mouse model. Most calbindin‐immunoreactive (IR) Renshaw cells survive to end stage but downregulate postsynaptic Chrna2 in presymptomatic animals. In motor neurons, some markers are downregulated early (NeuN, VAChT, Chondrolectin) and others at end stage (Calca). Early downregulation of presynaptic VAChT and Chrna2 was correlated with disconnection from Renshaw cells as well as major structural abnormalities of motor axon synapses inside the spinal cord. Renshaw cell synapses on motor neurons underwent more complex changes, including transitional sprouting preferentially over remaining NeuN‐IR motor neurons. We conclude that the loss of presynaptic motor axon input on Renshaw cells occurs at early stages of ALS and disconnects the recurrent inhibitory circuit, presumably resulting in diminished control of motor neuron firing. J. Comp. Neurol. 521:1449–1469, 2013. © 2012 Wiley Periodicals, Inc.     

A Multimodal Imaging Protocol, <Superscript>123</Superscript>I/<Superscript>99</Superscript>Tc-Sestamibi,SPECT, and SPECT/CT,in Primary Hyperparathyroidism Adds Limited Benefit for Preoperative Localization

Introduction

Focused parathyroidectomy in primary hyperparathyroidism (1°HPT) is possible with accurate preoperative localization and intraoperative PTH monitoring (IOPTH). The added benefit of multimodal imaging techniques for operative success is unknown.

Method

Patients with 1°HPT, who underwent parathyroidectomy in 2012–2014 at a single institution, were retrospectively reviewed. Only the patients who underwent the standardized multimodal imaging workup consisting of ¹²³I/⁹⁹Tc-sestamibi subtraction scintigraphy, SPECT, and SPECT/CT were assessed.

Results

Of 360 patients who were identified, a curative operation was performed in 96 %, using pre-operative imaging and IOPTH. Imaging analysis showed that ¹²³I/⁹⁹Tc-sestamibi had a sensitivity of 86 % (95 % CI 82–90 %), positive predictive value (PPV) 93 %, and accuracy 81 %, based on correct lateralization. SPECT had a sensitivity of 77 % (95 % CI 72–82 %), PPV 92 % and accuracy 72 %. SPECT/CT had a sensitivity of 75 % (95 % CI 70–80 %), PPV of 94 %, and accuracy 71 %. There were 3 of 45 (7 %) patients with negative sestamibi imaging that had an accurate SPECT and SPECT/CT. Of 312 patients (87 %) with positive uptake on sestamibi (93 % true positive, 7 % false positive), concordant findings were present in 86 % SPECT and 84 % SPECT/CT. In cases where imaging modalities were discordant, but at least one method was true-positive, ¹²³I/⁹⁹Tc-sestamibi was significantly better than both SPECT and SPECT/CT (p < 0.001). The inclusion of SPECT and SPECT/CT in 1°HPT imaging protocol increases patient cost up to 2.4-fold.

Conclusion

¹²³I/⁹⁹Tc-sestamibi subtraction imaging is highly sensitive for preoperative localization in 1°HPT. SPECT and SPECT/CT are commonly concordant with ¹²³I/⁹⁹Tc-sestamibi and rarely increase the sensitivity. Routine inclusion of multimodality imaging technique adds minimal clinical benefit but increases cost to patient in high-volume setting.

     

Postoperative Analgesia Due to Sustained-Release Buprenorphine,Sustained-Release Meloxicam,and Carprofen Gel in a Model of Incisional Pain in Rats (Rattus norvegicus)

Postoperative analgesia in laboratory rats is complicated by the frequent handling associated with common analgesic dosing requirements. Here, we evaluated sustained-release buprenorphine (Bup-SR), sustained-release meloxicam (Melox-SR), and carprofen gel (CG) as refinements for postoperative analgesia. The aim of this study was to investigate whether postoperative administration of Bup-SR, Melox-SR, or CG effectively controls behavioral mechanical and thermal hypersensitivity in a rat model of incisional pain. Rats were randomly assigned to 1 of 5 treatment groups: saline, 1 mL/kg SC BID; buprenorphine HCl (Bup HCl), 0.05 mg/kg SC BID; Bup-SR, 1.2 mg/kg SC once; Melox-SR, 4 mg/kg SC once; and CG, 2 oz PO daily. Mechanical and thermal hypersensitivity were tested daily from day–1 through 4. Bup HCl and Bup-SR attenuated mechanical and thermal hypersensitivity on days 1 through 4. Melox-SR and CG attenuated mechanical hypersensitivity–but not thermal hypersensitivity–on days 1 through 4. Plasma concentrations, measured by using UPLC with mass spectrometry, were consistent between both buprenorphine formulations. Gross pathologic examination revealed no signs of toxicity in any group. These findings suggest that postoperative administration of Bup HCl and Bup-SR—but not Melox-SR or CG—effectively attenuates mechanical and thermal hypersensitivity in a rat model of incisional pain.Abbreviations: Bup HCl, buprenorphine HCl; Bup-SR, sustained-release buprenorphine; CG, carprofen gel; Melox-SR, sustained-release meloxicamPostoperative analgesia is a vital aspect of laboratory animal medicine. Investigators have a responsibility to follow an effective and safe pain management protocol for research animals that have undergone surgical procedures. Pain and distress are serious animal welfare concerns that directly affect animal physiology and can result in altered research data.^1,17,30 Continued refinement of pre-, intra-, and postoperative pain management in rodents is necessary to improve animal wellbeing, obtain high-quality research data, and ensure compliance with standards set forth by the Guide for the Care and Use of Laboratory Animals.²¹Many classes of analgesics are available to veterinary practitioners, but in the laboratory setting, the options tend to be simpler and typically involve 1 of 2 drug classes, opioids and NSAID. Buprenorphine HCl (Bup HCl), a partial μ-opioid receptor agonist, has long been the ‘gold standard’ for postoperative analgesia in laboratory animals due to the drug''s prolonged plasma half-life and effective analgesic properties.^15,28 Buprenorphine effectively controls mild to moderate postoperative pain in rodents for 6 to 12 h.¹⁶ Because many rodent surgical procedures might cause pain for at least 48 h, researchers must handle these animals at least twice daily during this time period to readminister buprenorphine. Repeated dosing requires frequent handling of surgically manipulated animals, resulting in handling-associated stress.¹ In addition, handling an animal frequently likely is disruptive to its cagemates and potentially to animals in the same room. Because of their analgesic and antiinflammatory properties, NSAID are often used either in conjunction with or as an alternative to opioids to control pain in laboratory animals.^11,33 Meloxicam and carprofen are 2 NSAID that preferentially inhibit cyclooxygenase 2 and thus prostaglandin synthesis.^10,11 Although generally considered safe, reported side effects of NSAID include gastrointestinal ulceration, altered platelet function, and renal dysfunction.¹¹Novel formulations of opioid and NSAID analgesics have recently been introduced to the veterinary market and include sustained-release injectables,^2,5,14,22 gel-based oral compounds,^6,19 and transdermal patches.^13,18,25,37 Our group previously demonstrated the effectiveness of sustained-release buprenorphine (Bup-SR) in controlling mild to moderate incisional pain in rats.⁷ Another study found that Bup-SR successfully controlled orthopedic surgical pain in rats.¹⁴ These alternative formulations show great potential in decreasing the stress associated with frequent handling and dosing requirements. Many of these products are still considered new in the veterinary market, and few evidence-based recommendations for their use in laboratory animal species are available. The main goal of the current study was to refine postoperative analgesia by using longer-lasting or gel-formulation products. To this end, we investigated whether Bup-SR, sustained-release meloxicam (Melox-SR), or carprofen gel (CG) provided postoperative analgesia in the rat plantar incisional model according to results of behavioral testing. We hypothesized that Bup-SR, Melox-SR, and CG would provide effective postoperative analgesia as evidenced by reduced pain responses in this model.     

Dietary Changes Impact the Gut Microbe Composition in Overweight and Obese Men with Prostate Cancer Undergoing Radical Prostatectomy

Background

Diet and obesity influence prostate cancer risk and progression–effects that may be mediated through the gut microbiome.