Effectiveness of Low-Level Laser Therapy with a 915 Nm Wavelength Diode Laser on the Healing of Intraoral Mucosal Wound: An Animal Study and a Double-Blind Randomized Clinical Trial.

Background and objectives: Diode laser has been the most popular low-level laser therapy (LLLT) technique in dentistry due to its good tissue penetration, lower financial costs, small size for portable application, and convenience to use. A series of recent studies with 940 nm or 980 nm lasers demonstrated that LLLT showed positive effects after third molar extraction or periodontal flap surgery. However, the effects of LLLT on intraoral mucosal wound healing after surgical incision have not yet been determined in human clinical study. Materials and Methods: The present study was performed to determine the efficacy and safety of 915 nm wavelength low-level laser therapy (LLLT) in mucosal wound healing. A total of 108 Sprague-Dawley rats were used. They were divided into three groups: Abrasive wound group, immediate LLLT once group, and daily LLLT group. As a clinical study, a total of 16 patients with split-mouth design subjected to bilateral mandibular third molar extraction were allocated into the LLLT group and placebo group. The process of LLLT was performed on postoperative days 0, 1, and 7, and parameters related to wound healing were analyzed on days 1, 7, and 14. Results: Repeated laser irradiation promoted mucosal wound healing of the rats. In the clinical study, although there were no significant statistical differences between the LLLT and placebo groups in all inflammatory parameters, the early stage mucosal healing tendency of wound dehiscence was higher in the LLLT group than in the placebo group clinically on postoperative day 1. Conclusions: The present results showed that 915 nm LLLT could be applied safely as an auxiliary therapy for mucosal wound healing.

Topical treatments of Saussurea costus root and Thuja orientalis L. synergistically alleviate atopic dermatitis-like skin lesions by inhibiting protease-activated receptor-2 and NF-κB signaling in HaCaT cells and Nc/Nga mice.

ETHNOPHARMACOLOGICAL RELEVANCE: The root of Saussurea costus (Aucklandia lappa Decne, Aucklandiae Radix, SC) and Thuja orientalis L. (TOL) have been traditionally used as anti-inflammatory agents in Korea. However, they have not been studied for the efficacy of atopic dermatitis (AD) treatment, a chronic inflammatory skin disease. We investigated the efficacy of topical applications with 1,3-butyleneglycol extracts of SC and TOL to alleviate the symptoms of AD. MATERIALS AND METHODS: HaCaT cells and the dorsal skin of Nc/Nga mice had a local exposure of house mite extracts and 2,4-dinitrochlorobenzene (DNCB), respectively. After lesions developed, we topically applied 1,3-butylen glycol (vehicle; control), SC (30%), TOL (30%), or SC (15%)+TOL (15%) to the skin lesions for 5 weeks. The normal-control was not exposed to DNCB. The skin thickness, mast cell infiltration, serum immunoglobulin E (IgE) and IgG1 and gene expressions of interleukin (IL)-4, IL-13, and IFN-γ in the dorsal skin and HaCaT cells were measured. RESULTS: Chlorogenic acid (129.6±10.2µg/g) for SC and catechin and apigenin (93.4±13.2 and 16.9±1.3µg/g, respectively) for TOL were used as indicator compounds for the strength of the extracts. SC+TOL decreased the expression of protease-activated receptor-2 and ICAM-1 and the release of TNF-α and IL-6 in HaCaT cells activated by 3µg/mL house mite extracts in comparison to either of SC or TOL alone. In Nc/Nga mice challenged with DNCB, SC+TOL synergistically attenuated clinical symptoms of AD such as erythema, hemorrhage, edema, excoriation and dryness in the dorsal skin better than either SC or TOL alone. Histological analysis of the dorsal skin also showed that SC+TOL treatment significantly and additively decreased the inflammatory cellular infiltrate, including mast cells and eosinophils in comparison to either of SC or TOL. SC+TOL also decreased serum IgE and IgG1 levels and the expression of IFN-γ, IL-4, and IL-13 mRNA in dorsal skin in DNCB-treated Nc/Nga mice. CONCLUSION: SC+TOL relieved the symptoms of AD by reducing pro-inflammatory activity and over-activated immune responses. These data suggest that SC+TOL may be an effective alternative intervention for the management of AD.

Comparison of the Effects of Manual Acupuncture, Laser Acupuncture, and Electromagnetic Field Stimulation at Acupuncture Point BL15 on Heart Rate Variability.

The aim of this study was to compare the influences of manual acupuncture, laser acupuncture, and electromagnetic field stimulation on the autonomic nervous system. We monitored the heart rate variability before and after stimulation to check the influence on the autonomic nervous system. The heart rate variabilities at low frequency (LF; 0.04-0.15 Hz) and high frequency (HF; 0.15-0.4 Hz) were analyzed to acquire LF/HF ratio. Xinshu (BL15) was selected as the stimulation point. Methods included manual acupuncture with a 1-cm depth and laser acupuncture at a wavelength of 660 nm and output power of 50 mW. An electromagnetic field of 2 Hz and 460 gauss (46 mT) was chosen. The LF and the LF/HF ratio were found to be lower in the manual acupuncture and the electromagnetic field groups, but to be higher in the laser acupuncture group. The HF was found to be lower in the laser acupuncture group, but higher in the manual acupuncture and the electromagnetic field groups. In conclusion, we found that manual acupuncture and electromagnetic field stimulation at BL15 activated the parasympathetic nervous system, whereas laser acupuncture at BL15 activated the sympathetic nervous system.

Proteasome inhibitors with pyrazole scaffolds from structure-based virtual screening.

We performed a virtual screen of ∼340 000 small molecules against the active site of proteasomes followed by in vitro assays and subsequent optimization, yielding a proteasome inhibitor with pyrazole scaffold. The pyrazole-scaffold compound displayed excellent metabolic stability and was highly effective in suppressing solid tumor growth in vivo. Furthermore, the effectiveness of this compound was not negatively impacted by resistance to bortezomib or carfilzomib.

Electromagnetic acupuncture to enhance the effects of manual acupuncture on recovery from muscle fatigue of the quadriceps.

The aim of this study was to investigate a new method of manual acupuncture that used a magnetic field to stimulate only one acupoint vertically. We developed an eight-channel electromagnetic acupuncture (EMA) system that uses a solenoid-type electrode to insert the manual acupuncture needle into a hole in an electrode. We used a manual acupuncture needle for magnetic induction in order to penetrate vertically and deeply into tissues. In order to confirm the usefulness of EMA, we investigated the effects of treatment on muscle fatigue after strenuous knee extension/flexion exercises that had been performed by three groups: the nonstimulation, the manual acupuncture, and the EMA groups. Electromyograms showed that the median frequency (MF) in the EMA group had rapidly recovered after 4 minutes (p = 0.608), but that the peak torque had not recovered to the normal state (p < 0.05). Thus, we confirmed that compared with manual acupuncture, EMA resulted in better recovery from muscle fatigue.

Selective immunoproteasome inhibitors with non-peptide scaffolds identified from structure-based virtual screening.

As a major component of the crucial nonlysosomal protein degradation pathway in the cells, the proteasome has been implicated in many diseases such as Alzheimer's disease, Huntington's disease, inflammatory bowel diseases, autoimmune diseases, multiple myeloma (MM) and other cancers. There are two main proteasome subtypes: the constitutive proteasome which is expressed in all eukaryotic cells and the immunoproteasome which is expressed in immune cells and can be induced in other cell types. Majority of currently available proteasome inhibitors are peptide backbone-based, having short half-lives in the body. It is highly desirable to identify novel, immunoproteasome-selective inhibitors with non-peptide scaffolds for development of novel therapeutics. Through combined virtual screening and experimental studies targeting the immunoproteasome, we have identified a set of novel immunoproteasome inhibitors with diverse non-peptide scaffolds. Some of the identified inhibitors have significant selectivity for the immunoproteasome over the constitutive proteasome. Unlike most of the currently available proteasome inhibitors, these new inhibitors lacking electrophilic pharmacophores are not expected to form a covalent bond with proteasome after the binding. These non-peptide scaffolds may provide a new platform for future rational drug design and discovery targeting the immunoproteasome.

Use of pupil size to determine the effect of electromagnetic acupuncture on activation level of the autonomic nervous system.

Magnetic fields are widely considered as a method of treatment to increase the therapeutic effect when applied to acupoints. Hence, this study proposes a new method which creates significant stimulation of acupoints by using weak magnetic fields. We conducted this experiment in order to confirm the effect on the activation level of the autonomic nervous system by measuring pupil sizes in cases of stimulation by using manual acupuncture and electromagnetic acupuncture (EMA) at BL15. We selected 30 Hz of biphasic wave form with 570.1 Gauss. To confirm the biopotential by the magnetic flux density occurring in EMA that affected the activation of the autonomic nervous system, we observed the biopotential induced at the upper and the mid left and right trapezius. We observed a significant decrease in pupil size only in the EMA group (p < 0.05), thus confirming that EMA decreased the pupil size through activation of the parasympathetic nerve in the autonomic nervous system. Moreover, we confirmed that the amplitude of the biopotential which was caused by 570.1 Gauss was higher than ±20 µA. Thus, we can conclude that EMA treatment successfully activates the parasympathetic nerve in the autonomic nervous system by inducing a biotransformation by the induced biopotential.

Development and evaluation of a multi-frequency bioelectrical impedance analysis analyzer for estimating acupoint composition.

The purpose of this study was to suggest a new method of estimating acupoint compositions by using a multi-frequency bioelectrical impedance analysis (MF-BIA) method at 5 kHz, 50 kHz and 200 kHz within 2 cm of acupoints divided into local segments. To verify the system developed, we confirmed the stable occurrence of a constant current at every frequency, regardless of the impedance connected to the electrodes. Moreover, we found left and right distal bicep brachii aponeurosis to be identical by using ultrasound imaging, and we analyzed the repeatability of the findings by making 10 consecutive sets of measurements (p > 0.05). To evaluate the practical use of the acupoint composition, we used the MF-BIA analyzer to measure the left and right LU3, LU4, and LU9 at the lung meridian. We confirmed that the potentials generated were equal to the changes in the cell membrane function, which were caused by the applied frequency (p < 0.01). We also verified that the MF-BIA analyzer measurements corresponded to the acupoint components by comparing the left and right potentials generated (p > 0.05). Hence, we conclude that the MF-BIA analyzer can be used to estimate the acupoint composition based on the acupoint state.

Effects of torsemide on pharmacodynamics and pharmacokinetics of warfarin in humans and rats.

OBJECTIVES: This study aimed to evaluate the effects of torsemide on warfarin therapy in humans and rats. METHODS: For the animal study, rats were orally dosed with warfarin (0.13 mg/kg, control group) or warfarin (0.13 mg/kg) with torsemide (2 mg/kg, low dose group and 10 mg/kg, high dose group). The pharmacodynamic response of warfarin was assessed by measuring the international normalized ratio (INR) for 5 consecutive days following drug administration. For the human study, 191 patients on warfarin with mechanical heart valves were followed up retrospectively. The stable dose was calculated as the mean dose in INR levels of 2-3 for 3 consecutive times. KEY FINDINGS: In the animal study, the INR, maximum plasma concentration (Cmax ) and area under the plasma drug concentration-time curve (AUC0-∞ ) of (S)-warfarin in the high dose group were significantly higher than in other groups (P < 0.05). Compared with the control group, Cmax and AUC0-∞ of (R)-warfarin in the high and low dose groups were higher, whereas the volume of distribution/bioavailability and clearance/bioavailability were significantly lower (P < 0.05). In the univariate analysis of the clinical study, diuretics significantly lowered stable warfarin doses (P = 0.016) (5.07 ± 1.78 mg/day vs 5.77 ± 1.81 mg/day). After controlling confounding variables, the effects of diuretics were found to lower the warfarin dose by 0.464 mg. CONCLUSIONS: It was concluded that warfarin dose needs to be lowered when it is used concomitantly with diuretics.

Wnt-signaling-mediated antiosteoporotic activity of porcine placenta hydrolysates in ovariectomized rats.

Anti-osteoporotic effects of two types of porcine placenta hydrolysates (PPH) were evaluated in ovariectomized (OVX) rats orally administered PPH without (WPPH) or with (NPPH) ovarian hormones (1 g/kg bw/day). PPH groups were compared with OVX rats with estrogen replacement (0.1 mg/kg bw conjugated estrogen; EST), or dextrose (placebo; OVX-control) All rats received high-fat/calcium-deficient diets for 12 weeks. NPPH contained less estrogen and progesterone, but more essential amino acids, whereas the opposite was true for WPPH. NPPH decreased body weight and peri-uterine fat pads, and maintained uterus weight. NPPH rats had higher femur and lumbar spine bone mass density compared to controls; but less than those of EST rats. Serum phosphorus and urinary calcium and phosphorus levels were reduced in NPPH rats compared to OVX-controls. Serum bone-specific alkaline phosphatase, osteocalcin, and bone turnover marker levels were reduced NPPH rats compared to OVX-controls. WPPH produced results similar to those of NPPH, but less significant. Both NPPH and estrogen upregulated low-density lipoprotein receptor-related protein 5 and ß-catenin in OVX rats, while the expression of dickkopf-related protein 1 was suppressed. In conclusion, NPPH exerted anti-osteoporotic effects by activating osteogenesis and stimulating Wnt signaling, possibly mediated by the various amino acids and not ovarian hormones.

Comparison of 2 methods of non-invasive treatment between transcutaneous electrical stimulation and pulsed electromagnetic field stimulation as replacement of invasive manual acupuncture.

The aim of this study was to find the non-invasive optimal alternative method for Manual Acupuncture. Existing researches had reported that Transcutaneous Electrical Acupoint Stimulation (TEAS) was an effective treatment method instead of manual acupuncture. In place of the TEAS, we suggested the Pulsed Electromagnetic Fields (PEMFs). Thus, we designed the PEMFs system which can stimulate only an acupoint. There have been no researches which reported therapeutic effect when stimulating at an identical acupoint by TEAS and PEMFs. Hence, this study investigated the therapeutic effect on the muscle fatigue after the strenuous knee extension/flexion exercise by two stimulations. We selected the stimulation method of both TEAS and PEMFs by using 2Hz biphasic rectangular wave pulse and pulse width 0.2ms. The magnetic flux was the 30.92mT (309.2gauss) at 2 Hz. The electromyogram (EMG) and the maximal voluntary contraction (MVC) at rectus femoris were measured. The Median Frequency (MF) at TEAS group was significantly effective at 6 minutes (p=0.499). The PEMFs group was recovered to the MF rapidly after 4 minutes (p=0.166). The results of the peak torque indicated that both non-stimulation group and TEAS group did not recover to the peak torque at pre-exercise during the recovery period (p<0.05). In contrast, the significant treatment effect of PEMFs group was found after 14 minutes (p=0.135). The results of this study demonstrated that PEMFs were better than TEAS as a non-invasive method to replace the manual acupuncture.