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May 2026 DOI 10.14302/issn.2574-4518.jsdr-25-5773
Peres de Sousa LucasCorresponding author
Introduction Sleep quality is a fundamental determinant of human health and well-being. Modified Intravascular Laser Irradiation of Blood (ILIB), a non-invasive therapeutic modality, has emerged as a potential intervention for sleep-related disturbances. Proposed mechanisms include reduced blood viscosity and platelet aggregation, activation of superoxide dismutase, increased oxygen bioavailability, enhanced microcirculation, elevated serotonin levels, and decreased cortisol concentrations—physiological processes intricately involved in sleep regulation, mood modulation, and the stress response. Objective To evaluate the effects of Modified Intravascular Laser Irradiation of Blood (ILIB) on sleep quality in individuals with self-reported sleep disturbances. Methods A randomized, placebo-controlled clinical trial was conducted with participants who reported poor sleep quality. Subjects were randomly assigned to one of two groups: the intervention group received ILIB using a 660 nm red laser, while the control group received a placebo treatment (light emission with sub-therapeutic power, <1 mW). Both groups underwent the same treatment schedule. Sleep quality was assessed at baseline and after six treatment sessions using the Pittsburgh Sleep Quality Index (PSQI) and the Epworth Sleepiness Scale (ESS). Results Participants in the ILIB group showed statistically significant improvements in the primary outcome of global sleep quality. PSQI scores decreased from 10.24 at baseline to 6.47 post-treatment. ESS scores showed a non-significant change from 10.44 to 10.12. These results suggest enhanced overall sleep quality and reduced sleep latency, although the observed reduction in daytime sleepiness did not reach statistical significance. Conclusion Modified Intravascular Laser Irradiation of Blood appears to be a promising non-invasive approach for improving sleep quality. The clinical outcomes observed are comparable to those reported in both pharmacological and behavioral sleep interventions, particularly in terms of PSQI improvements. These preliminary findings support the need for further research to clarifyunderlying mechanisms, optimize treatment parameters (e.g., dosimetry and duration), and expand outcome assessments to include biomarkers and polysomnographic data.
Mar 2026 DOI 10.14302/issn.2574-4518.jsdr-26-6010
Marmann PeterCorresponding author
Background/Aim Sleep disturbances are common and are associated with impaired daytime functioning, reduced quality of life, and increased health risks. Non-pharmacological neuromodulatory interventions have gained interest as alternatives to hypnotic medication. Pulsed electromagnetic field (PEMF) therapy has been proposed as a non-invasive approach to improve sleep quality and recovery, but evidence from large, well-controlled trials remains limited. The objective of this study was to evaluate the efficacy and safety of pulsed magnetic field therapy (PMT) on sleep quality, sleep-related symptoms, daytime functioning, and well-being in adults with heterogeneous sleep complaints. Materials and Methods In this remote, randomized, double-blind, placebo-controlled trial, 217 adults reporting non-restorative sleep, difficulties initiating sleep, or frequent nocturnal awakenings were assigned to active PMT using a PEMF device (Night Harmony Female/Male protocol) or a sham application for three weeks. Primary outcomes were changes in the Pittsburgh Sleep Quality Index (PSQI) global score and self-rated sleep satisfaction, restfulness, and sleep initiation difficulties. Secondary outcomes included sleep diary measures, daytime functioning, well-being (WHO-5), symptom burden (MYMOP), and daytime sleepiness (Epworth Sleepiness Scale). Analyses followed the intention-to-treat principle using ANCOVA with baseline values of the respective parameter as covariate. Results Both groups showed significant improvements over time in global sleep quality and most secondary outcomes (p < 0.001). Between-group differences in PSQI global score were not significant (p = 0.314). However, active PMT resulted in significantly greater improvements in subjective sleep satisfaction (p = 0.02) and restfulness (p = 0.02), particularly among participants with moderate to severe baseline sleep disturbances (p < 0.001 for both). Sleep continuity measures improved similarly in both groups. No serious adverse events were reported. Conclusions PMT produced modest but significant improvements in subjective restorative aspects of sleep beyond placebo effects and was well tolerated. Further studies using objective sleep measures and longer follow-up are warranted.
Jun 2024 DOI 10.14302/issn.2379-7835.ijn-24-5117
Hoon Kim DoCorresponding author
In this study, the efficacy and safety of DKB-131 (extract of Siraitiagrosvenorii) in adults of both genders presenting mild symptoms of knee arthritis were evaluated in comparison to a placebo. This clinical trial was randomized, double-blind, multicenter, and lasted for 12 weeks. A total of 120 participants with Visual Analogue Scale (VAS) scores of 30 mm or higher in the knee area and Kellgren & Lawrence Grade I or II knee arthritis on X-ray were enrolled, with 60 subjects randomized to receive DKB-131 and 60 subjects receiving placebo. Following 12 weeks of consumption, the change in K-WOMAC total score assessed in the per protocol (PP) set revealed a reduction of 21.86±15.98 points in participants who received DKB-131 (p<0.0001), whereas those in the placebo group exhibited a reduction of 14.92±16.66 points (p<0.0001). This demonstrated a statistically significant difference between the test groups (p=0.0389). Additionally, significant differences were observed between the DKB-131 and placebo groups in the changes in K-WOMAC pain (p=0.0157) and physical function (p=0.0447). For the secondary efficacy endpoint, the change in Visual Analogue Scale (VAS) scores, analyzed in the PP set after 12 weeks of consumption, the test group showed a reduction of 17.82±13.80 mm (p<0.0001), while the control group exhibited a reduction of 11.81±13.99 mm (p<0.0001), indicating a statistically significant difference between the test groups (p=0.0359). Safety evaluations including hematological tests, biochemical tests, and urinalysis revealed no clinically significant differences between the consumption groups. Additionally, vital signs (pulse, blood pressure) and anthropometric measurements (body weight) did not exhibit clinically significant differences between the consumption groups, confirming the safety of DKB-131. We propose that the consumption of DKB-131 is safe for humans and may contribute to joint health. Trial registration (CRIS.NIH.go.Kr): KCT0008527
Feb 2021 DOI 10.14302/issn.2328-0182.japst-21-3700
Y. Alkarib SuadCorresponding author
Department of Pharmaceutics, College of Pharmacy, Karary University, Sudan
Objectives The present study addresses evaluation of acacia-guar gum combination as an enteric former for tablet coating aiming to add knowledge on how develop the ability of enteric forming ability of acacia-guar combination. Methods Five formulations of enteric coating solution incorporating guar gum as delayed release polymers along with film coating material acacia gum followed by CMC and glycerin as plasticizer and coloring agents were prepared to coat placebo tablet cores. Different enteric coating formulations organized in different acacia : guar gum ratios as 1:1, 1:2, 1:3, 1:4 and 1:6 were sprayed on placebo tablets surface resulted different delayed coated tablets (F1,F2,F3,F4 &F5) respectively. General appearance and physical parameters were evaluated of each. Enteric coated tablets that revealed promising properties were subjected to accelerated stability study for 3 months to explore the influences of physical aging on tablet coat properties. Results Physical parameters of enteric coated tablets post coating within the range of pharmacopeia specification. The disintegration test was carried out in pH 1.2 and pH 6.8 at 37ºC. F1, F2 and F3 enteric tablets disintegrated immediately with no acid resistance compared F4 and F5 enteric tablets showed good acid resistance coat with smooth tablet surfaces and no coat defects. F5 formula contain acacia: guar gum as 1:6 ratio showed delayed release for 30min in pH 1.2 and 15min in phosphate buffer. The study statistically analyzed and concluded that, an efficient and stable acacia-guar enteric coat is achievable with no effect on tablets physical parameters. Guar gum at 60% as a delayed tablet coating material capable of protecting the tablets core from being released in acidic media and be release in the alkaline buffer as well as stable coat under accelerated storage for three months.
Jun 2019 DOI 10.14302/issn.2576-6694.jbbs-19-2784
Cesar Pinto Leal-Junior ErnestoCorresponding author
Laboratory of Phototherapy and Innovative Technologies in Health, Nove de Julho University – UNINOVE, Sao Paulo, Brazil.
The aim of this clinical study was to determine the efficacy of bilateral alternating somatosensory stimulation for the management of stress and anxiety during and after the Trier Social Stress Test (TSST), a laboratory procedure for reliably inducing stress in human subjects. For this, a randomized, placebo-controlled, triple-blinded clinical trial of 80 qualified subjects was conducted. Subjects were randomized into two groups, a treatment group (n=40) and a control (placebo) group (n=40). Metrics of emotional stress assessed were a subjective rating of the level of emotional stress and salivary cortisol levels, both obtained at 3 timepoints: before treatment (baseline), immediately following completion of the TSST, and after 20 minutes of rest following completion of the TSST. Results showed that the treatment group had a statistically greater decrease in the subjective rating of stress relative to the control group both immediately following the TSST and 20 minutes after the TSST. Salivary cortisol levels in the treatment group were also lower than the control group at those same time points. These results suggest that bilateral alternating somatosensory stimulation may be effective in reducing subjective levels of stress and anxiety. It also may actively attenuate stress-related cortisol levels, which may reflect a mechanism for reducing cortisol-induced inflammation back to baseline after exposure to stressful situations.
Apr 2016 DOI 10.14302/issn.2474-3585.jpmc-15-704
Rott DavidCorresponding author
Cardiac Rehabilitation Institute, Leviev Heart Center, The Chaim Sheba Medical Center, Tel Hashomer Israel
Objective: Statins are highly effective medications for reducing low-density lipoprotein cholesterol concentrations and cardiovascular events. Their most common side effects are a variety of myopathic complaints, possibly due to reduced circulating Coenzyme Q10 (CoQ10) levels. We sought to determine whether CoQ10 supplementation decreases the rate of myalgia in patients with statin-related myalgia. Methods: Patients treated with a statin for clinical indications who reported statin induced myalgia were eligible. Patients were randomized to treatment with CoQ10 120 mg/day (17 patients) or placebo (20 patients) in a double-blind manner. Treatment was continued for 12 weeks. All patients were instructed to continue taking their prescribed statin as usual. Myalgia score was assessed before intervention and then weekly, for 12 weeks of therapy, using a visual analogue scale (VAS). Results: Over 12 weeks of treatment, myalgia score gradually decreased in both the treatment group and placebo group to the same extent (from 6.2 to 3.3 in the treatment group and from 5.9 to 3.1 in the placebo group), without significant differences between the groups. No significant change was noted between the two groups in the number of patients tolerated statin therapy. Conclusions: CoQ10 does not appear to decrease the rate of myalgia when compared to placebo in patients with statin-related myalgia.
Jan 2013 DOI 10.14302/issn.2328-0182.japst-12-99
C Korte WolfgangCorresponding author
Center for Laboratory Medicine, St. Gallen;
To date, platelet aggregation studies have not been formally evaluated in persons receiving Etodolac, a preferential cyclooxygenase-2 (COX-2) inhibitor. Our purpose was to investigate the influence of Etodolac in therapeutic (analgesic) doses (300 mg every 12h) on platelet aggregation as compared to placebo in healthy volunteers. Platelet aggregation, the primary efficacy variable in this trial, was performed according to the Born method with platelet rich plasma; it was evaluated as maximal platelet aggregation induced by 3 substances (adenosine diphosphate (ADP), epinephrine, collagen); each of these substances was used at 3 different concentrations. No significant difference in platelet aggregation as assessed by Born aggregometry was seen in volunteers treated with etodolac or placebo. Etodolac - applied in regular analgesic doses to volunteers - does not show an inhibitory effect on platelet aggregation and therefore seems an attractive analgesic substance for the perioperative setting.
Sep 2022 DOI 10.14302/issn.2641-4538.jphi-22-4238
Bavbek SevimCorresponding author
Department of Chest Disease, Division of Allergy and Clinical Immunology, Ankara University, School of Medicine, Ankara, Turkey
The safety of cyclooxygenase (COX)-2 inhibitors has been tested in patients who had cross-reactive hypersensitivity reactions (HSRs) to nonsteroidal anti-inflammatory drugs (NSAIDs). However, these studies have been mainly done before the current classification of NSAID hypersensitivity and cross-reaction between COX-2 inhibitors has been rarely reported.We aimed to assess tolerability of COX-2 inhibitors and to evaluate the cross-reactivity between them in cross-reactive phenotype of NSAID hypersensitivity. The diagnosis was based on clinical features, reliable history of HSRs to at least two chemically different NSAIDs, and/or positive provocation tests with implicated NSAIDs in 151 patients. Single-blind, oral challenges with 1/4 and 3/4 divided doses of placebo, nimesulide, meloxicam, and celecoxib, as COX-2 inhibitors, were performed. The most common cross-reactive phenotype was NSAID-induced urticaria/angioedema (56.3%). Positive reactions to meloxicam, nimesulide, and celecoxib challenges were observed in 23/140 (16.4%), 7/33 (21.2%), and none of six patients, respectively. Overall, 24 patients were tested with two, one was tested with three COX-2 inhibitors. Six (31.6%) of 19 patients with meloxicam intolerance reacted to nimesulide provocation. Nimesulide, meloxicam, and celecoxib appeared safe alternatives in cross-reactive phenotypes of NSAID hypersensitivity. Although celecoxib has the most favorable tolerability, cross-reactivity among COX-2 inhibitors seems to be possible.
Feb 2020 DOI 10.14302/issn.2379-7835.ijn-20-3201
Carolina Garcia de las Ballonas Campolina AnaCorresponding author
Department of Biochemistry and Immunology, Biological Sciences Institute, Federal University of Minas Gerais, Belo Horizonte, MG, Brazil
Fibromyalgia (FM) is a condition of chronic and widespread pain, with several associated symptoms. Previous studies suggested that gluten could influence the severity and frequency of FM symptoms. This work aimed to assess the impact of a gluten-free diet (GFD) in the symptoms and severity of this disease. Fourteen patients with previous FM diagnosis were kept on a gluten-free diet for eight weeks (Phase 1). After that, they were held on the gluten-free diet and received capsules of isolated rice protein (placebo) for seven days, followed by capsules containing 8.4g/day vital gluten for additional seven days (Phase 2). Questionnaires evaluating the number and severity of FM symptoms, the impact of FM on daily routine as well as inflammatory blood markers were assessed in each phase. Results showed that after eight weeks of GFD, we observed a reduction in the impact of FM on daily routine and number of symptoms and sensitive points. However, a seven days challenge with 8.4g of gluten did not worsen these symptoms or the inflammatory markers compared with the placebo challenge. We concluded that the gluten-free diet was associated with the attenuation of main symptoms and improvement of life quality in FM patients. Nonetheless, gluten challenge had no impact on those parameters, suggesting that gluten is not the major dietary component responsible for these improvements. Further studies are needed to elucidate the relationship between gluten intake and fibromyalgia.
Aug 2019 DOI 10.14302/issn.2470-5020.jnrt-19-2797
A Best-Popescu CatherineCorresponding author
University of Illinois College of Medicine, Urbana-Champaign, Urbana, IL, USA (Barry J. Riskin, MD)
Background There is substantial evidence, from well-conducted epidemiological studies, that low vitamin D levels are correlated with increased risk for MS, and multiple case control studies have implicated the involvement of vitamin D deficiency in MS etiology. Narrow-band Ultraviolet B (NB-UVB; 300nm - 311 nm) induced vitamin D production has not previously been studied in a multiple sclerosis (MS) randomized placebo-controlled trial (RCT). Objectives To investigate NB-UVB induced vitamin D production, immunomodulation and MS symptomology following NB-UVB phototherapy in a MS cohort. Methods Using a blinded RCT study design, twelve individuals 18 years or older with MS were enrolled and assigned (1:1) into individualized NB-UVB dose (10-30kJ/m) phototherapy, or into placebo treatment, delivered 3 times per week, for 8-weeks. Serum vitamin D levels, walking performance, strength, cognitive function, mood and circulating progenitor cells (CPCs: CD34+CD45dim), monocyte populations (Intermediate CD14+CD16+, Classical CD14+CD16-), and T regulatory cell (CD4+/CD25+/FoxP3+Tregs) count were assesed. The data were analyzed by 2 x 3 mixed factor ANOVA. Results A statistically significant condition by time interaction on vitamin D levels (F=7.14, p<.005, partial η2=.42) was identified. NB-UVB phototherapy may provide immunomodulation in a select group of MS individuals. Conclusion UVB phototherapy corrects vitamin D deficiency. This study adds to the growing research investigating UVB treatment in MS.
Jan 2019 DOI 10.14302/issn.2379-7835.ijn-18-2469
Kawasaki YoheiCorresponding author
Biostatistics Section, Clinical Research Center, Chiba University Hospital, 1-8-1 Inohana, Chuo-ku, Chiba-shi, Chiba, 260-8677, Japan
Background Docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) are categorized as omega-3 poly unsaturated fatty acids (PUFAs) that are present in fish oil, etc. DHA and EPA omega-3 PUFAs have a well-established fasting serum triglycerides (TG) lowering effect that may result in normal lipidemia in hyperlipidemic patients. In general, omega-3 PUFAs, such as DHA and EPA, can be ingested easily, and because they are highly safe, they are assumed to be suitable for controlling fasting serum TG in the serum of those who do not require drug treatment. To the best of our knowledge, however, almost all systematic reviews on the effects of omega-3 PUFAs on lowering fasting serum TG are directed at patients fulfilling the diagnostic criteria of dyslipidemia. Objectives To review and confirm the preventive effect of omega-3 PUFAs against hypertriglyceridemia or the effect on nondrug treatment in patients with a mild disease, a systematic review was conducted to determine whether there was a fasting serum TG-lowering effect in subjects without disease and those with a slightly higher triglyceride level who consumed DHA and/or EPA orally compared to those with placebo or no intake of DHA and/or EPA. Search Methods We evaluated articles from searches of PubMed (1946-February 2016), Ichushi-Web (1977-February 2016), and J Dream III (JST Plus, 1981-February 2016; JMED Plus, 1981-February 2016). The keywords were set as follows: “DHA” or “docosahexaenoic acid” or “EPA” or “eicosapentaenoic acid” and “TG” or “triglyceride” or “triglycerol” or “triacylglycerol” or “neutral lipid.”. In addition to the literature group obtained by the database search, we included participants not suffering from any disease (i.e., excluding mild hypertriglyceridemia). Eligibility Criteria Before the test selection process, the following inclusion criteria were defined. Participants were healthy men and women including those with mild hypertriglyceridemia (fasting serum TG level, 150-199 mg/dL [1.69-2.25 mmol/L)). Intervention was defined as orally ingested DHA and/or EPA. Comparison was made to placebo intake or no intake of DHA and/or EPA. Results were measured for the fasting serum TG level. The test design was RCT, and quasi-RCT. Data Abstraction Various characteristics were extracted from original reports using a standardized data extraction form, including the author of the study, research year, research design, subject characteristics (sex, age, sample size), period, dose of DHA and/or EPA (mg/day), and comparison group. Main Results We identified 37 documents for review. Among the 37 reports used to integrate literature results, 25 revealed a decrease in fasting serum TG level due to the oral ingestion of DHA and/or EPA. Sixteen studies on subjects without disease and 21 on subjects with slightly higher fasting serum TG levels were separated and stratified analysis was conducted. Ten of the 16 (normal TG participant) and 15 of the 21 studies (slightly higher TG participant) respectively, indicated that at least 133 mg/day of DHA and/or EPA intervention provided a statistically significant decrease in the fasting serum TG level between an intervention group versus a placebo group.
Dec 2018 DOI 10.14302/issn.2379-7835.ijn-18-2491
Iacobelli StefanoCorresponding author
Janus Pharma S.r.l., Via Giacomo Peroni 386, 00131 Roma, Italy.
Objective: To evaluate the efficacy and safety of a novel tomato-based food supplement on the lower urinary tract symptoms (LUTS) of patients with benign prostatic hyperplasia (BPH). Methods: Twenty patients with BPH were enrolled in this observational study. They were assigned to consume daily a sachet of Lycoprozen® (5 grams) dissolved in water for two months. Results: All patients successfully completed the Lycoprozen scheduled regimen and the IPSS (International Prostatic Symptom Score) questionnaire before and after treatment. No side effects due to treatment were noticed. In this preliminary study, we have found that Lycoprozen® significantly reduced the LUTS severity (paired t-test, two-tailed p value < 0.0001). The IPSS mean values before and after the treatment were 16.95+6.0 SD (range 31-6) and 12.2+4.9 SD (range 20-2), respectively. Conclusions: Based on these data, Lycoprozen® may represent a suitable alternative option for the treatment of symptomatic BPH patients which worth of further testing in a phase 2 prospective randomized double blind placebo controlled study. The treatment was without side effects and acceptance among patients was high.
Nov 2013 DOI 10.14302/issn.2324-7339.jcrhap-13-304
Garavaglia Wilson AlexandriaCorresponding author
St. Louis College of Pharmacy, 4588 Parkview Place, St. Louis, MO 63110.
Antiretrovirals have traditionally been associated with much toxicity. Newer antiretrovirals are considered much less toxic relative to older antiretrovirals. Upon its FDA-approval in 2009, raltegravir’s adverse drug reaction profile was found to be similar to placebo. However, recently there have been reports of increased creatine kinase and rhabdomyolysis following the initiation of raltegravir. We describe a 52-year-old, African-American man who developed rhabdomyolysis after starting raltegravir for HIV. Rhabdomyolysis resolved upon discontinuation of raltegravir. Use of the Naranjo adverse drug reaction probability scale indicated a probable relationship (score of 6). Although raltegravir is a well-tolerated antiretroviral, clinicians should be aware of the possibility of rhabdomyolysis when prescribing this medication.