Computational fluid dynamics modeling of coronary artery blood flow using OpenFOAM: Validation with the food and drug administration benchmark nozzle model.

Cardiovascular disease (CVD), a global health concern, particularly coronary artery disease (CAD), poses a significant threat to well-being. Seeking safer and cost-effective diagnostic alternatives to invasive coronary angiography, noninvasive coronary computed tomography angiography (CCTA) gains prominence. This study employed OpenFOAM, an open-source Computational Fluid Dynamics (CFD) software, to analyze hemodynamic parameters in coronary arteries with serial stenoses. Patient-specific three-dimensional (3D) models from CCTA images offer insights into hemodynamic changes. OpenFOAM breaks away from traditional commercial software, validated against the FDA benchmark nozzle model for reliability. Applying this refined methodology to seventeen coronary arteries across nine patients, the study evaluates parameters like fractional flow reserve computed tomography simulation (FFRCTS), fluid velocity, and wall shear stress (WSS) over time. Findings include FFRCTS values exceeding 0.8 for grade 0 stenosis and falling below 0.5 for grade 5 stenosis. Central velocity remains nearly constant for grade 1 stenosis but increases 3.4-fold for grade 5 stenosis. This research innovates by utilizing OpenFOAM, departing from previous reliance on commercial software. Combining qualitative stenosis grading with quantitative FFRCTS and velocity measurements offers a more comprehensive assessment of coronary artery conditions. The study introduces 3D renderings of wall shear stress distribution across stenosis grades, providing an intuitive visualization of hemodynamic changes for valuable insights into coronary stenosis diagnosis.

Methylcobalamin in Combination with Early Intervention of Low-Intensity Pulsed Ultrasound Potentiates Nerve Regeneration and Functional Recovery in a Rat Brachial Plexus Injury Model.

This study evaluated and compared the functional recovery and histopathological outcomes of treatment involving low-intensity pulsed ultrasound (LIPUS) and methylcobalamin (B12) on brachial plexus injury (BPI) in an experimental rat model. Three days after BPI, the rats were assigned to receive either LIPUS or methylcobalamin alone or in combination consecutively for 12 days. Serial changes in sensory and motor behavioral responses, as well as morphological and immunohistochemical changes for substance P (SP), ionized calcium-binding adapter molecule 1 (iba1), brain-derived neurotrophic factor (BDNF), and S100 were examined 28 days after BPI as the outcome measurements. Early intervention of LIPUS and methylcobalamin, whether alone or in combination, augmented the sensory and motor behavioral recovery as well as modulated SP and iba1 expression in spinal dorsal horns, BDNF, and S100 in the injured nerve. Moreover, the combined therapy with its synergistic effect gave the most beneficial effect in accelerating functional recovery. In view of the effective initiation of early recovery of sensory and motor functions, treatment with LIPUS and methylcobalamin in combination has a potential role in the clinical management of early-phase BPI.

Early Intervention of Cold-Water Swimming on Functional Recovery and Spinal Pain Modulation Following Brachial Plexus Avulsion in Rats.

Brachial plexus avulsion (BPA) causes peripheral nerve injury complications with motor and sensory dysfunction of the upper limb. Growing evidence has shown an active role played by cold-water swimming (CWS) in alleviating peripheral neuropathic pain and functional recovery. This study examined whether CWS could promote functional recovery and pain modulation through the reduction of neuroinflammation and microglial overactivation in dorsal horn neurons at the early-stage of BPA. After BPA surgery was performed on rats, they were assigned to CWS or sham training for 5 min twice a day for two weeks. Functional behavioral responses were tested before and after BPA surgery, and each week during training. Results after the two-week training program showed significant improvements in BPA-induced motor and sensory loss (p < 0.05), lower inflammatory cell infiltration, and vacuole formation in injured nerves among the BPA-CWS group. Moreover, BPA significantly increased the expression of SP and IBA1 in dorsal horn neurons (p < 0.05), whereas CWS prevented their overexpression in the BPA-CWS group. The present findings evidenced beneficial rehabilitative effects of CWS on functional recovery and pain modulation at early-stage BPA. The beneficial effects are partially related to inflammatory suppression and spinal modulation. The synergistic role of CWS combined with other management approaches merits further investigation.

Ultra-Low Frequency Transcutaneous Electrical Nerve Stimulation on Pain Modulation in a Rat Model with Myogenous Temporomandibular Dysfunction.

Masticatory myofascial pain (MMP) is one of the most common causes of chronic orofacial pain in patients with temporomandibular disorders. To explore the antinociceptive effects of ultra-low frequency transcutaneous electrical nerve stimulation (ULF-TENS) on alterations of pain-related biochemicals, electrophysiology and jaw-opening movement in an animal model with MMP, a total of 40 rats were randomly and equally assigned to four groups; i.e., animals with MMP receiving either ULF-TENS or sham treatment, as well as those with sham-MMP receiving either ULF-TENS or sham treatment. MMP was induced by electrically stimulated repetitive tetanic contraction of masticatory muscle for 14 days. ULF-TENS was then performed at myofascial trigger points of masticatory muscles for seven days. Measurable outcomes included maximum jaw-opening distance, prevalence of endplate noise (EPN), and immunohistochemistry for substance P (SP) and µ-opiate receptors (MOR) in parabrachial nucleus and c-Fos in rostral ventromedial medulla. There were significant improvements in maximum jaw-opening distance and EPN prevalence after ULF-TENS in animals with MMP. ULF-TENS also significantly reduced SP overexpression, increased MOR expression in parabrachial nucleus, and increased c-Fos expression in rostral ventromedial medulla. ULF-TENS may represent a novel and applicable therapeutic approach for improvement of orofacial pain induced by MMP.

Ultrasound Acupuncture for Oxaliplatin-induced Peripheral Neuropathy in Patients With Colorectal Cancer: A Pilot Study.

BACKGROUND: Oxaliplatin is frequently used in the treatment of metastatic colorectal cancer. However, peripheral neuropathy is a severe adverse effect of oxaliplatin that may persist and impact quality of life. OBJECTIVE: To assess the potential effects of ultrasound acupuncture for the alleviation of symptoms related to oxaliplatin-induced peripheral neuropathy (OIPN) among patients with metastatic colorectal cancer. DESIGN: Prospective cohort pilot study. SETTING: Education and research hospital. PARTICIPANTS: Patients with a diagnosis of stage II-IV colorectal cancer undergoing oxaliplatin-based treatment regimens who experienced OIPN symptoms (n = 17). INTERVENTIONS: Pulsed therapeutic ultrasound (1 MHz) at bilateral acupuncture points of PC6, PC7, BL60, and KI1 was administered for 5 minutes per point daily for 12 days. MAIN OUTCOME MEASUREMENTS: Pain Quality Assessment Scale (PQAS), Chemotherapy-induced Neurotoxicity Questionnaire (CINQ), quantitative touch-detection threshold, cold-trigger pain withdrawal latency, and quality of life (EORTC QLQ-C30) were measured at baseline (day 0), pre-intervention (day 12, post wash-out period), post-intervention (day 24), and final follow-up (day 54). A P value of less than .05 was considered statistically significant. RESULTS: Scores of PQAS and CINQ significantly improved after ultrasound acupuncture at post-intervention and follow-up compared to both baseline and pre-intervention. Similar trends were also observed for the quantitative sensory testing, where touch-detection threshold significantly decreased and cold-trigger pain withdrawal latency significantly increased after ultrasound acupuncture. Patients also showed an improvement on quality of life outcomes as measured by QLQ-C30 post-intervention and at follow-up. CONCLUSIONS: Ultrasound acupuncture could be an effective intervention for OIPN symptoms for patients with colorectal cancer. However, larger and randomized clinical trials with placebo controls are needed to confirm such effects.

Increased substance P-like immunoreactivities in parabrachial and amygdaloid nuclei in a rat model with masticatory myofascial pain.

This study explores the involvement of substance P (SP) in the parabrachial nucleus (PBN) and central amygdaloid nucleus (CeA) in the nociception-emotion link and of rats with masticatory myofascial pain (MMP) induced by chronic tetanic eccentric muscle contraction. A total of 18 rats were randomly and equally assigned for MMP (MMP group) and sham-MMP induction (sMMP group). MMP was induced by electrical-stimulated repetitive tetanic eccentric contraction of the masseter muscle for 14 consecutive days. Myofascial trigger points in the masseter muscle were identified by palpable taut bands, increased prevalence of endplate noise (EPN), focal hypoechoic nodules on ultrasound and restricted jaw opening. All animals were killed for morphological and SP immunohistochemical analyses. Chronic tetanic eccentric contraction induced significantly thicker masseter muscle confirmed by hypoechogenicity, increased prevalence and amplitudes of EPN, and limited jaw opening. Immunohistochemically, the SP-like positive neurons increased significantly in PBN and CeA of the MMP group. Our results suggested that MMP increases the SP protein levels in PBN and CeA, which play important roles in MMP-mediated chronic pain processing as well as MMP-related emotional processes.

Blockade of Cardiac Proton Pump Impairs Ventricular Remodeling Through a Superoxide-DDAH-Dependent Pathway in Infarcted Rats.

BACKGROUND: Proton pump inhibitors (PPIs) are frequently used to prevent or treat peptic ulcers. Recently, PPIs have been shown to increase the risk of myocardial infarction. The purpose of this study was to determine whether PPIs adversely affect ventricular remodeling in infarcted rats. METHODS: Male Wistar rats were randomly assigned to receive either vehicle, omeprazole, omeprazole + vitamin C, omeprazole + olmesartan, or famotidine treatment for 4 weeks starting 24 hours after inducing myocardial infarction by ligating coronary arteries. RESULTS: Compared with vehicle-treated infarcted rats, omeprazole-treated infarcted rats had significant changes with reduced myocardial vitamin C levels, increased oxidant production, and decreased dimethylarginine dimethylaminohydrolase 2 (DDAH2) activity, which in turn increased asymmetric dimethylarginine (ADMA) levels and impaired ventricular remodeling. With gastric protection similar to omeprazole, the H2 blocker famotidine had no effect on ventricular remodeling. In contrast to the in vivo results, the ex vivo study showed similar superoxide and DDAH2 protein levels between vehicle- and omeprazole-treated infarcted rats, suggesting involvement of gastric vitamin C uptake rather than myocardial vitamin C in mediating the impaired axis of vitamin C-superoxide-DDAH2 in the in vivo measurements. The administration of PPIs was associated with impaired DDAH2 expression and increased myocardial ADMA, which impaired ventricular remodeling after infarction. These effects were prevented by the coadministration of vitamin C or olmesartan. CONCLUSIONS: Our results indicate that the administration of PPIs was associated with impaired DDAH2 expression and increased myocardial ADMA by reducing gastric vitamin C uptake, which impaired ventricular remodeling after infarction.

Early intervention of swimming exercises attenuate articular cartilage destruction in a rat model of anterior cruciate ligament and meniscus knee injuries.

AIM: The anterior cruciate ligament (ACL) and meniscus injuries often cause post-traumatic knee osteoarthritis (PTOA), which can place great limitations on patients. But to date there is no effective therapy to delay the progression of cartilage destruction in PTOA. This study aimed to compare the effects of early versus delayed swimming exercise on the chondroprotective effects in a rat PTOA model with ACL and meniscus injuries. MAIN METHODS: Thirty-two adult male Sprague-Dawley rats received unilateral ACL transection and medial meniscectomy (ACLMT). These were randomly allocated to four groups: early swimming (eSW), delayed swimming (dSW), sham-operated early swimming (sham-eSW) and sham-operated delayed swimming (sham-dSW). Swimming (30 min per session) continuing for 28 days was started three days and three months after ACLMT surgery as a protocol for eSW and dSW intervention. Cartilage quality was assessed by Mankin HHGS examination (H&E, Safranin-O stain) and collagen type II (CoII) and matrix metalloproteases-13 (MMP13) immunohistochemistry. KEY FINDINGS: ACLMT induced the PTOA histopathological changes, inhibited CoII and enhanced MMP13 expressions in cartilage for both sham-eSW and sham-dSW groups. eSW intervention significantly enhanced CoII expression and suppressed MMP13 overexpression in superficial and transitional zones of cartilage, as well as better Mankin scores, corresponding to sham-swimming controls (P < 0.05). dSW intervention provided less enhancement of CoII expression and improvement of histopathological scoring, but significantly reduced MMP13 overexpression compared to animals in eSW (P < 0.05). SIGNIFICANCE: Early intervention by swimming at very early stages of cartilage damage provides greater benefits than delayed intervention when PTOA has already developed.

Early Intervention with Therapeutic Low-Intensity Pulsed Ultrasound in Halting the Progression of Post-traumatic Osteoarthritis in a Rat Model.

Anterior cruciate ligament (ACL) and meniscus injuries are highly correlated with post-traumatic knee osteoarthritis (PTOA). The aim of this study was to examine whether early intervention with low-intensity pulsed ultrasound (LIPUS) at an intensity of 0.1 W/cm2 helps delay PTOA progression. A PTOA model was established by ACL transection and meniscectomy in male Sprague-Dawley rats. LIPUS intervention (1.0 MHz, 0.1 W/cm2) started on the third day after surgery and continued for 4 consecutive wk. Histopathological analyses and immunoassays of collagen type II and matrix metallopeptidase 13 in joints were conducted. Results indicated that compared with the sham treatment, LIPUS significantly reduced Mankin scores, inflammatory cells and matrix metallopeptidase 13 expression and increased collagen type II expression in rats with PTOA (p < 0.05). Early intervention with LIPUS has beneficial effects on delaying cartilage degradation by reducing synovial inflammation and matrix metallopeptidase 13 expression, as well as enhancing collagen type II expression in cartilage.

Analgesic Effects of Transcutaneous Ultrasound Nerve Stimulation in a Rat Model of Oxaliplatin-Induced Mechanical Hyperalgesia and Cold Allodynia.

This study investigated the effects and underlying mechanisms of therapeutic ultrasound (TUS) in a rat model of oxaliplatin-induced peripheral neuropathy. Animals received a total of eight injections with oxaliplatin (4 mg/kg), administered at 3-d intervals. TUS intervention (1 MHz, 0.5 W/cm2) started on the fifth oxaliplatin administration and continued for 10 consecutive d. Sensory behavioral examinations, protein levels of transient receptor potential channels (TRPM8 and TRPV1) in dorsal root ganglia (DRG) and substance P (SP) in spinal dorsal horn were examined. Results indicated that TUS can reduce mechanical and cold hyper-responsive behaviors caused by repeated administration of oxaliplatin. Oxaliplatin-related increases in protein levels of TRPM8 in DRG and SP in the dorsal horn were also reduced after TUS. Taken together, the results revealed beneficial effects of TUS on oxaliplatin-induced mechanical hyperalgesia and cold allodynia and suggested involvement of TUS biochemicals in suppressing TRPM8 in DRG and SP in spinal cords.

Effects of hippotherapy on body functions, activities and participation in children with cerebral palsy based on ICF-CY assessments.

PURPOSE: To evaluate the effects of hippotherapy on body functions, activities, and participation in children with CP of various functional levels by using the International Classification of Functioning, Disability and Health-Children and Youth (ICF-CY) checklist. METHODS: Fourteen children with cerebral palsy (CP) (3-8 years of age) were recruited for a 36-week study composed of baseline, intervention, and withdrawal phases (12 weeks for each phase, ABA design). Hippotherapy was implemented for 30 min once weekly for 12 consecutive weeks during the intervention phase. Body Functions (b) and Activities and Participation (d) components of the ICF-CY checklist were used as outcome measures at the initial interview and at the end of each phase. RESULTS: Over the 12 weeks of hippotherapy, significant improvements in ICF-CY qualifiers were found in neuromusculoskeletal and movement-related functions (b7), mobility (d4) and major life areas (d8) and, in particular, mobility of joint functions (b710), muscle tone functions (b735), involuntary movement reaction functions (b755), involuntary movement functions (b765), and play (d811) (all p < 0.05) when compared with baseline. CONCLUSION: This study demonstrated the beneficial effects of hippotherapy on body functions, activities, and participation in children with CP. Implications for Rehabilitation ICF-CY provides a comprehensive overview of functioning and disability and constitutes a universal language for identifying the benefits of hippotherapy in areas of functioning and disability in children with CP. In children with CP, hippotherapy encourages a more complementary approach that extends beyond their impairments and limitations in body functions, activities, and participation. The effect of hippotherapy was distinct from GMFCS levels and the majority of improvements were present in children with GMFCS levels I-III.

Laser acupuncture attenuates oxaliplatin-induced peripheral neuropathy in patients with gastrointestinal cancer: a pilot prospective cohort study.

BACKGROUND: Oxaliplatin is a platinum compound that is widely used in the treatment of some solid tumours. Oxaliplatin-induced peripheral neuropathy (OIPN) in the upper and lower extremities is the major adverse side effect and represents the main dose-limiting factor of this drug. The aim of this single-arm study was to evaluate the feasibility and effects of laser acupuncture (LA) in the treatment of OIPN in patients with advanced gastrointestinal cancers. METHODS: 17 gastrointestinal cancer survivors (14 colorectal and 3 gastric cancers), who had been treated with oxaliplatin-based chemotherapies, were recruited. Low-level laser stimulation (50 mW) bilaterally at PC6, PC7, PC8, P9, LU11, SP6, KI3, BL60, KI1, and KI2 was administered for 20 min/point for 12 sessions over 4 weeks. The pain quality assessment scale (PQAS), chemotherapy-induced neurotoxicity questionnaire (CINQ), oxaliplatin-specific neurotoxicity scale (OSNS), quantitative touch-detection threshold (using von Frey filaments), and cold-triggered pain withdrawal latency (using the cold-water immersion test) were measured before and after completion of the 12 treatment sessions. RESULTS: PQAS, CINQ, and OSNS scores, as well as touch-detection threshold and cold-trigger pain withdrawal latency all improved significantly after LA in the cancer patients with OIPN (p<0.05). LA significantly relieved both oxaliplatin-induced cold and mechanical allodynia and also decreased the incidence and severity of neurotoxicity symptoms in the patients' upper and lower extremities and impact on their daily activities (all p<0.05). CONCLUSIONS: Following treatment with LA, neurotoxicity symptoms were significantly improved in cancer patients with OIPN. Further randomised controlled trials are needed to evaluate the role of LA as a therapeutic option in the management of OIPN.

Acupuncture at distant myofascial trigger spots enhances endogenous opioids in rabbits: a possible mechanism for managing myofascial pain.

BACKGROUND AND AIM: Acupuncture applied at myofascial trigger points (MTrPs) of distant anatomical regions, to reduce pain in a patient's area of primary complaint, is one strategy that is available to manage myofascial pain. However, the endogenous opioid-mediated analgesic mechanism of distant acupuncture associated with pain control is still unclear. This aims of this study were to evaluate the changes in enkephalin and ß-endorphin in serum, spinal cord, dorsal root ganglion (DRG) and muscle induced by acupuncture at distant myofascial trigger spots (MTrSs, similar to human MTrPs) in rabbits, to explore its underlying remote analgesic mechanism. METHODS: Acupuncture at MTrSs of a distant muscle (gastrocnemius) was performed either for one session or five daily sessions in rabbits. The levels of enkephalin and ß-endorphin in proximal muscle (biceps femoris), serum, DRGs and spinal cords (L5-S2) were then determined by immunoassay immediately and 5 days after treatment. RESULTS: Immediately after treatment, acupuncture comprising both one dose and five doses significantly enhanced spinal enkephalin expression and serum ß-endorphin levels (p<0.05). However, only five-dose acupuncture significantly enhanced the ß-endorphin levels in the biceps femoris and DRGs (p<0.05), while 1-dose acupuncture did not (p>0.05). Furthermore, 5 days after treatment, significantly increased levels of spinal enkephalin and serum ß-endorphin persisted in animals that received 5-dose acupuncture (p<0.05). CONCLUSIONS: This study demonstrates that interactions within the endogenous opioid system may be involved in the remote effects of acupuncture treatment and could be a potential analgesic mechanism underlying MTrP pain management.

Synergistic effects of low-level laser and mesenchymal stem cells on functional recovery in rats with crushed sciatic nerves.

Transplantation of mesenchymal stem cells (MSCs) has been proposed to exert beneficial effects on peripheral nerve regeneration after a peripheral nerve injury, but the functional recovery in the denervated limb is still limited. In this study, we used low-level laser therapy (LLLT) as an adjunct therapy for MSC transplantation on the functional recovery of crushed sciatic nerve in rats. Peripheral nerve injury was induced in 48 Sprague-Dawley rats by crushing the unilateral sciatic nerve, using a vessel clamp. The animals with crushed injury were randomly divided into four groups: control group, with no treatment; MSC group, treated with MSC alone; LLLT group, treated with LLLT alone; and MSCLLLT group, treated with a combination of MSC and LLLT. The sciatic function index (SFI), vertical activity of locomotion (VA) and ankle angle (AA) of rats were examined for functional assessments after treatment. Electrophysiological, morphological and S100 immunohistochemical studies were also conducted. The MSCLLLT group showed a greater recovery in SFI, VA and AA, with significant difference from MSC, LLLT and control groups (p < 0.05). Moreover, markedly enhanced electrophysiological function and expression of S100 immunoreactivity, as well as fewer inflammatory cells and less vacuole formation were also demonstrated after nerve crush injury in the MSCLLLT group when compared with the groups receiving a single treatment (p < 0.05). MSC transplantation combined with LLLT could achieve better results in functional recovery than a conventional treatment of MSC or LLLT alone. LLLT has a synergistic effect in providing greater functional recovery with MSC transplantation after nerve crush injury.

Enhanced functional recovery from sciatic nerve crush injury through a combined treatment of cold-water swimming and mesenchymal stem cell transplantation.

OBJECTIVE: Although regimens of stem cell implantation can elicit functional recovery following peripheral nerve injury, the degree of outcome is still limited. This study evaluated the synergistic effects of cold-water swimming (CWS) and mesenchymal stem cell (MSC) transplantation on functional recovery of crushed sciatic nerve in rats. METHOD: Forty Sprague-Dawley rats that had their sciatic nerve crushed during surgery were randomly divided into four groups: MSCCWS group, treated with combination of MSC and CWS; MSC group, treated with MSC alone; CWS group, treated with CWS alone; and non-treated group, without any treatments. The sciatic function index (SFI), vertical activity (VA), ankle activity (AA) and electrophysiological study were examined before, immediately after surgery, after the treatment and after 4  weeks from treatment. Morphological and S100 immunohistochemical studies were also performed. RESULTS: The MSCCWS group showed a greater improvement in SFI, VA, AA, peak amplitudes and onset latencies of compound muscle action potential (CMAP) in sciatic nerve and infiltration of immune cells with significant difference from the MSC, CWS and non-treated groups (P < 0.05). CONCLUSIONS: MSC transplantation combined with CWS could achieve better results in functional recovery than a single treatment of MSC alone or CWS alone in nerve crush injury.

Fluence-dependent effects of low-level laser therapy in myofascial trigger spots on modulation of biochemicals associated with pain in a rabbit model.

Evidence strongly supports that low-level laser therapy (LLLT) is an effective physical modality for the treatment of pain associated with myofascial trigger points (MTrP). However, the effect of laser fluence (energy intensity in J/cm(2)) on biochemical regulation related to pain is unclear. To better understand the biochemical mechanisms modulated by high- and low-fluence LLLT at myofascial trigger spots (MTrSs; similar to human MTrPs) in skeletal muscles of rabbits, the levels of ß-endorphin (ß-ep), substance P (SP), tumor necrosis factor-α (TNF-α), and cyclooxygenase-2 (COX-2) were investigated in this study. New Zealand rabbits (2.5-3.0 kg in weight) were used in this study. High-fluence LLLT (27 J/cm(2)), low-fluence LLLT (4.5 J/cm(2)), or sham operations were applied on MTrSs of biceps femoris of rabbits for five sessions (one session per day). Effects of LLLT at two different fluences on biceps femoris, dorsal root ganglion (DRG), and serum were determined by ß-ep, SP, TNF-α, and COX-2 immunoassays. LLLT irradiation with fluences of 4.5 and 27 J/cm(2) at MTrSs can significantly reduce SP level in DRG. LLLT with lower fluence of 4.5 J/cm(2) exerted lower levels of TNF-α and COX-2 expression in laser-treated muscle, but LLLT with higher fluence of 27 J/cm(2) elevated the levels of ß-ep in serum, DRG, and muscle. This study demonstrated fluence-dependent biochemical effects of LLLT in an animal model on management of myofascial pain. The findings can contribute to the development of dosage guideline for LLLT for treating MTrP-induced pain.

Sitagliptin attenuates sympathetic innervation via modulating reactive oxygen species and interstitial adenosine in infarcted rat hearts.

We investigated whether sitagliptin, a dipeptidyl peptidase-4 (DPP-4) inhibitor, attenuates arrhythmias through inhibiting nerve growth factor (NGF) expression in post-infarcted normoglycemic rats, focusing on adenosine and reactive oxygen species production. DPP-4 bound adenosine deaminase has been shown to catalyse extracellular adenosine to inosine. DPP-4 inhibitors increased adenosine levels by inhibiting the complex formation. Normoglycemic male Wistar rats were subjected to coronary ligation and then randomized to either saline or sitagliptin in in vivo and ex vivo studies. Post-infarction was associated with increased oxidative stress, as measured by myocardial superoxide, nitrotyrosine and dihydroethidium fluorescent staining. Measurement of myocardial norepinephrine levels revealed a significant elevation in vehicle-treated infarcted rats compared with sham. Compared with vehicle, infarcted rats treated with sitagliptin significantly increased interstitial adenosine levels and attenuated oxidative stress. Sympathetic hyperinnervation was blunted after administering sitagliptin, as assessed by immunofluorescent analysis and western blotting and real-time quantitative RT-PCR of NGF. Arrhythmic scores in the sitagliptin-treated infarcted rats were significantly lower than those in vehicle. Ex vivo studies showed a similar effect of erythro-9-(2-hydroxy-3-nonyl) adenine (an adenosine deaminase inhibitor) to sitagliptin on attenuated levels of superoxide and NGF. Furthermore, the beneficial effects of sitagliptin on superoxide anion production and NGF levels can be reversed by 8-cyclopentyl-1,3-dipropulxanthine (adenosine A1 receptor antagonist) and exogenous hypoxanthine. Sitagliptin protects ventricular arrhythmias by attenuating sympathetic innervation via adenosine A1 receptor and xanthine oxidase-dependent pathways, which converge through the attenuated formation of superoxide in the non-diabetic infarcted rats.

The fluence effects of low-level laser therapy on inflammation, fibroblast-like synoviocytes, and synovial apoptosis in rats with adjuvant-induced arthritis.

OBJECTIVE: The aim of this study was to evaluate the effect of low-level laser therapy (LLLT) operating at low and high fluences on joint inflammation, fibroblast-like synoviocytes (FLS), and synovial apoptosis in rats with adjuvant-induced arthritis. BACKGROUND DATA: Rheumatoid arthritis (RA) is characterized by pronounced inflammation and FLS proliferation within affected joints. Certain data indicate that LLLT is effective in patients with inflammation caused by RA; however, the fluence effects of LLLT on synovium are unclear. METHODS: Monoarthritis was induced in adult male Sprague-Dawley rats (250-300 g) via intraarticular injection of complete Freund's adjuvant (CFA) into the tibiotarsal joint. Animals were irradiated 72 h after CFA administration with a 780 nm GaAlAs laser at 4.5 J/cm2 (30 mW, 30 sec/spot) and 72 J/cm2 (80 mW, 180 sec/spot) daily for 10 days. After LLLT, the animals were euthanized and their arthritic ankles were collected for histopathological analysis, immunoassays of tumor necrosis factor (TNF)-α, matrix metallopeptidase (MMP)3 and 5B5, and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assays. RESULTS: LLLT at a fluence of 4.5 J/cm2 significantly reduced infiltration of inflammatory cells and expressions of TNF-α-, MMP3- and 5B5-like immunoreactivities, as well as resulting in more TUNEL-positive apoptotic cells in the synovium. No significant changes were observed in these biochemicals and inflammation in arthritic animals treated with 72 J/cm2. CONCLUSIONS: LLLT with low fluence is highly effective in reducing inflammation to sites of injury by decreasing the numbers of FLS, inflammatory cells, and mediators in the CFA-induced arthritic model. These data will be of value in designing clinical trials of LLLT for RA.

Remote dose-dependent effects of dry needling at distant myofascial trigger spots of rabbit skeletal muscles on reduction of substance P levels of proximal muscle and spinal cords.

BACKGROUND: Dry needling at distant myofascial trigger points is an effective pain management in patients with myofascial pain. However, the biochemical effects of remote dry needling are not well understood. This study evaluates the remote effects of dry needling with different dosages on the expressions of substance P (SP) in the proximal muscle, spinal dorsal horns of rabbits. METHODS: Male New Zealand rabbits (2.5-3.0 kg) received dry needling at myofascial trigger spots of a gastrocnemius (distant muscle) in one (1D) or five sessions (5D). Bilateral biceps femoris (proximal muscles) and superficial laminaes of L5-S2, T2-T5, and C2-C5 were sampled immediately and 5 days after dry needling to determine the levels of SP using immunohistochemistry and western blot. RESULTS: Immediately after dry needling for 1D and 5D, the expressions of SP were significantly decreased in ipsilateral biceps femoris and bilateral spinal superficial laminaes (P < .05). Five days after dry needling, these reduced immunoactivities of SP were found only in animals receiving 5D dry needling (P < .05). CONCLUSIONS: This remote effect of dry needling involves the reduction of SP levels in proximal muscle and spinal superficial laminaes, which may be closely associated with the control of myofascial pain.

Late Intervention-Related Complication - A Huge Subepicardial Hematoma.

UNLABELLED: A 75-year-old man had a history of triple vessel coronary artery disease. In August 2009, he had undergone successful percutaneous coronary intervention to the left circumflex coronary artery (LCX) for management of an in-stent restenosis (ISR) lesion. However, in September 2010, he began experiencing recurrent episodes of exertional chest pain. Chest radiography showed the left cardiac border bulging upwards. Transthoracic echocardiography and chest computed tomography revealed a huge oval mass of about 10.4 cm × 7.9 cm × 8.6 cm, which showed calcification and was obliterating the LCX. Subsequent coronary angiography revealed significant instent restenosis, with extravasation of a small amount of contrast material at the stent location, suggesting that the coronary artery had ruptured. We implanted a polytetrafluoroethylene-covered stent to seal the coronary perforation and to release the occlusion. The patient was symptom-free and had an uneventful outcome until the 1-year follow up. KEY WORDS: Coronary artery perforation; Covered stent; Hematoma.