Prevalence of saliva immunoglobulin A antibodies reactive with severe acute respiratory syndrome coronavirus 2 among Japanese people unexposed to the virus.

While the COVID-19 pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) poses a threat to public health as the number of cases and COVID-19-related deaths are increasing worldwide, the incidence of the virus infection is extremely low in Japan compared with many other countries. To explain this uncommon phenomenon, we investigated the prevalence of naturally occurring ("natural") antibodies, focusing on those of the secretory immunoglobulin A (sIgA) form, reactive with SARS-CoV-2 among Japanese people. One hundred and eighty healthy Japanese volunteers of a wide range of age who had been considered to be unexposed to SARS-CoV-2 participated in this study. Saliva samples and blood samples were collected from all of the 180 participants and 139 adults (aged ≥ 20 years) included therein, respectively. The determination of saliva IgA antibodies, mostly comprising sIgA antibodies, as well as serum IgA and immunoglobulin G antibodies, reactive with the receptor binding domain of the SARS-CoV-2 spike-1 subunit proteins was conducted using an enzyme-linked immunosorbent assay. The major findings were that 52.78% (95% confidence interval, 45.21%-60.25%) of the individuals who had not been exposed to SARS-CoV-2 were positive for saliva IgA antibodies with a wide range of levels between 0.002 and 3.272 ng/mL, and that there may be a negative trend in positivity for the antibodies according to age. As we had expected, a frequent occurrence of assumable "natural" sIgA antibodies reactive with SARS-CoV-2 among the studied Japanese participant population was observed.

[Drug properties of fosravuconazole L-lysine ethanolate (NAILIN® Capsules 100†mg), a new oral azole therapeutic for onychomycosis: an analysis based on non-clinical and clinical trial data].

Ravuconazole is a fourth generation azole exerting strong antifungal activity, with low drug-drug interaction and hepatic dysfunction risks. Fosravuconazole l-lysine ethanolate (fosravuconazole; NAILIN® Capsules 100 mg) was developed as a ravuconazole prodrug. Ravuconazole exerts strong antifungal activity against various pathogenic fungi including dermatophytes and Candida. Through prodrug formation, pharmacokinetic improvement was achieved, and bioavailability after oral administration reached 100%. The plasma ravuconazole concentration became 10-35 times higher than with current oral anti-onychomycosis drugs, and showed good skin and nail tissue transition plus tissue retention. This improvement obtained with fosravuconazole reflects its superior pharmacokinetic properties. We conducted a clinical trial with fosravuconazole orally administered once a day (100 mg ravuconazole) for 12 weeks in Japanese onychomycosis patients. The ravuconazole concentration in nail tissues exceeded the MIC90 against dermatophytes, even after treatment completion. Furthermore, the placebo-controlled, double-blind, comparative trial showed significantly superior effects (at 48 weeks after starting treatment, with a complete cure rate of 59.4%, a marked clinical improvement rate of 83.1%, and a mycological cure rate by direct microscopy of 82.0%). The major adverse reactions were laboratory abnormalities and gastrointestinal disorders with no severe symptoms, suggesting good tolerability. Fosravuconazole has fewer drug-drug interactions, is not affected by food, and is also expected to improve medication adherence since the administration period is only 12 weeks and there is no drug-free period as required with pulse therapy. Thus, fosravuconazole has many favorable pharmacological properties and can reasonably be expected to become a new oral treatment option for onychomycosis.

The Molecular Identification and Antifungal Susceptibilities of Aspergillus Species Causing Otomycosis in Tochigi, Japan.

Aspergillus species are the most common pathogenic fungi involved in otomycosis, an infection of the outer ear canal. In this study, we examined the incidence of Aspergillus infections and the antifungal susceptibilities of 30 Aspergillus species isolates from patients with otomycosis who visited Saiseikai Utsunomiya Hospital between August 2013 and July 2016. Based on the morphological test results, the strains were identified as Aspergillus niger sensu lato (20 strains), A. terreus sensu lato (7 strains), and A. fumigatus sensu lato (3 strains). In contrast, the molecular identifications based on analyzing the isolates' partial ß-tubulin gene sequences revealed them to be A. niger sensu stricto (12 strains), A. tubingensis (8 strains), A. terreus sensu stricto (7 strains), and A. fumigatus sensu stricto (3 strains). The antifungal susceptibility test results indicated that strains of A. tubingensis and A. niger sensu stricto displayed lower susceptibilities to ravuconazole, compared with the other isolates. The Aspergillus strains from this study showed low minimum inhibitory concentrations toward the azole-based drugs efinaconazole, lanoconazole, and luliconazole. Therefore, these topical therapeutic agents may be effective for the treatment of otomycosis.

Efficacy of Luliconazole Against Broad-Range Filamentous Fungi Including Fusarium solani Species Complex Causing Fungal Keratitis.

PURPOSE: Fungal keratitis can be difficult to medically treat. Topical antifungals are usually applied empirically as the initial option in treating fungal keratitis. Natamycin (NAT) and/or voriconazole (VRCZ) have been widely used in the treatment of fungal keratitis. However, Fusarium solani species complex (FSSC), which are the dominant species of fungal keratitis, are resistant to VRCZ. This study investigated in vitro efficacy of luliconazole (LLCZ), a new imidazole antifungal, against FSSC and other filamentous fungi. METHODS: A total of 18 Fusarium isolates and 7 others were grown on potato dextrose agar at 30 and 37°C. For Fusarium, species identification and phylogenetic tree analysis were performed based on elongation factor-1α (EF-1α) DNA sequencing. The broth microdilution method was used for antifungal susceptibility testing of 11 antifungal drugs including LLCZ. RESULTS: The 18 identified Fusarium isolates belonged to FSSC (n = 13), Fusarium oxysporum species complex (FOSC; n = 2), Fusarium chlamydosporum species complex (FCSC; n = 1), Fusarium incarnatum-equiseti species complex (FIESC; n = 1), and Fusarium fujikuroi species complex (FFSC; n = 1). We further divided 13 FSSC isolates into 3 clades, FSSC5 (n = 8), FSSC3 + 4 (n = 4), and FSSC9-a (n = 1), with 8 FSSC strains growing at 37°C. LLCZ showed lowest minimum inhibitory concentrations (MICs) against all tested filamentous fungi, with a MIC90 against the Fusarium species of 0.06 µg/mL, whereas MIC90 for NAT and VRCZ were 4 and 8 µg/mL, respectively. CONCLUSIONS: LLCZ has the strongest in vitro antifungal activity among all drugs used against broad-range filamentous fungi including FSSC. LLCZ may potentially be a new medical treatment option for fungal keratitis.

Potential of Ravuconazole and its Prodrugs as the New OralTherapeutics for Onychomycosis.

Onychomycosis is a fungal infection of the nail apparatus caused by dermatophytes, Candida and non-dermatophytic molds. It is highly prevalent in the general population worldwide and also responsible for significant morbidity and complications and does not usually cure itself. Thus, the condition needs to be treated in view of physical and psychological problems produced. Currently, oral medications using terbinafine are the most effective therapy, but it has relatively limited therapeutic success, particularly for long-term management. Such existing oral therapies are associated with high recurrence rates and treatment failure, as well as with potential adverse events and drug-drug interactions. In the light of these issues, development of more efficacious and safer alternatives for the treatment of onychomycosis is warranted.Ravuconazole and its prodrugs are promising new drug candidates for oral therapy of onychomycosis, among which a water-soluble prodrug, mono-lysine phosphoester derivative (E1224 or BFE1224) is in the most advanced stage of clinical development; a Phase II dose-finding study has been successfully completed and Phase III comparative studies are in progress in Japan.This review aims to summarize our current status of knowledge and information on ravuconazole and its prodrugs, particularly BFE1224, as the potential oral treatment option for onychomycosis. It also summarize the clinical features of onychomycosis with particular stress on its etiology, epidemiology, and current therapeutic options and their limitations. Given its clinical usefulness, BFE1224 may become a valuable addition to the current armamentarium for the treatment of onychomycosis.

Vascular effects and safety of supplementation with shark liver oil in middle-aged and elderly males.

Shark liver oil (SLO) has long been used as a traditional health food, with a particular benefit for vascular health, in Japan. The aim of this study was to assess the effect of dietary supplementation with SLO on arterial stiffness and peripheral microvascular function in otherwise healthy middle-aged and older males with slightly increased arterial stiffness. A randomized, double-blind, placebo-controlled, parallel study design was used to assign 41 healthy males with a mean age of 59.0±4.0 years (range, 45-69 years) to either SLO (n=21) or placebo (n=20) treatment for eight weeks. The effects on arterial stiffness and peripheral microvascular function were assessed by the cardio-ankle vascular index (CAVI) and by measurement of hand blood flow to cutaneous tissues using a laser Doppler perfusion imaging (LDPI) technique, respectively. Although the magnitude of the changes in the CAVI value during the eight-week intervention for the SLO group did not significantly differ from that for the placebo group, the changes in the CAVI value for the former group were significantly associated (r=0.575, P<0.01) with age. It was also found that the LDPI values at week 8 were significantly lowered (P<0.05) compared with the baseline values in the placebo group, while no change was observed in the SLO group, resulting in a significant difference in the changes between the two groups (P=0.002). Neither SLO supplementation-related adverse side-effects nor any abnormal changes in routine laboratory tests, including lipid profiles and anthropometric and haemodynamic parameters, were observed throughout the intervention. SLO may have the potential to safely improve vascular health in middle-aged and elderly males.

Improvement of liver function by the administration of oyster extract as a dietary supplement to habitual alcohol drinkers: A pilot study.

Alcoholic liver disease (ALD) is characterized by elevated serum γ-glutamyltransferase (GGT) activity with hepatic steatosis, hepatitis or occasionally fibrosis that may progress to cirrhosis. The potential therapeutic role of oyster extract (OE) or OE-containing dietary supplements (OE supplement) in ALD has seldom been evaluated. In the present study, 84 adults who had an alcohol-drinking habit and marginally high serum GGT levels were enrolled in a randomized, double-blind, placebo-controlled feeding trial to study the effect on alcohol-impaired liver function as reflected by an increased serum level of GGT, as well as the safety, of an OE supplement. The subjects were randomized to receive either an OE supplement (OE group) or placebo (placebo group). There were 42 subjects (31 males and 11 females) in each group, and all the enrolled subjects entered the study. Four individuals (5%) dropped out for reasons unassociated with the study and 6 other subjects were excluded from the efficacy analysis because they did not maintain the required frequency of alcohol intake. As a result, 38 subjects in the placebo group and 36 in the OE group underwent efficacy assessment. Assays of GGT and other liver enzymes were performed at baseline (week 0) and at weeks 4, 8 and 12 of the intervention period. The mean serum levels of GGT in the placebo group gradually increased, while those in the OE group tended to decrease, although no significant within-group differences were observed for either group. A significant between-group difference in the change of mean GGT from baseline was, however, found at week 12 (P=0.049). No OE supplement-associated untoward side-effects nor any abnormal changes in routine laboratory tests and anthropometric parameters were observed throughout the 12-week intervention. An OE supplement shows promise in reducing risk factors associated with ALD in adults with an alcohol intake habit.

[In vitro antifungal activity of ravuconazole against isolates of dermatophytes and Candida species from patients with dermatomycoses].

The in vitro activity of ravuconazole (RVCZ) was compared with those of itraconazole (ITCZ) and terbinafine (TBF) against 73 dermatophyte isolates and 18 Candida spp. isolates recovered from patients with dermatomycosis at 4 dermatological clinics in Japan in 2011. The dermatophyte isolates consisted of Trichophyton rubrum (n=51), Trichophyton mentagrophytes (n=20 : these strains were not identified by molecular phylogenetic analysis.), Trichophyton tonsurans (n=1), and Microsporum canis (n=1). The Candida spp. isolates comprised C. albicans (n=11), C. parapsilosis (n=5), C. guilliermondii (n=1), and C. pseudohaemulonii (n=1). RVCZ was highly active against all dermatophytes and all Candida spp. : the geometric mean (GM) MICs for T. rubrum and T. mentagrophytes were 0.035 µg/mL and MICs for T. tonsurans and M. canis were ≤ 0.03 µg/mL, and GM MICs for C. albicans and C. parapsilosis were ≤ 0.03 µg/mL and MICs for C. guilliermondii and C. pseudohaemulonii were 0.25 and ≤ 0.03 µg/mL, respectively. Compared to RVCZ, ITCZ showed similar anti-dermatophytic and anti-Candida activities, while TBF had a slightly higher anti-dermatophytic but a markedly lower anti-Candida activity. These results suggest that RVCZ is a potential candidate systemic antifungal therapy against onychomycosis and other dermatomycoses that are refractory to topical antifungal therapy.

How histopathology can contribute to an understanding of defense mechanisms against cryptococci.

Invasive fungal infections, particularly those considered opportunistic, have become a common and significant complication of procedures performed in advanced contemporary medicine. Among such infections, cryptococcosis, which is usually caused by infection with Cryptococcus neoformans and Cryptococcus gattii, is particularly problematic because this fungal infection occurs in immunocompromised and apparently immunocompetent individuals. It has been largely accepted that Cryptococcus species are recognized by cellular receptors and that Th1-type immune responses play an important role in defense mechanisms against the yeast. However, the interaction between the yeast and host tissue varies depending on the characteristics of the yeast and the immune status of the host. To gain a better understanding of the pathophysiology of cryptococcosis, we wish to emphasize the usefulness of histopathological examinations, because it allowed more detailed information of an extremely complex interaction between the causative yeasts and tissue response. In the present review, we describe the pathophysiology of cryptococcosis as largely revealed in our previous histopathological investigations of the experimental infection.

Effect of acacia polyphenol on glucose homeostasis in subjects with impaired glucose tolerance: A randomized multicenter feeding trial.

Numerous in vitro and animal studies, as well as clinical trials have indicated that plant-derived polyphenols exert beneficial effects on glucose intolerance or type 2 diabetes. This clinical study aimed to investigate the effects of acacia polyphenol (AP) on glucose and insulin responses to an oral glucose tolerance test (OGTT) in non-diabetic subjects with impaired glucose tolerance (IGT). A randomized, double-blind, placebo-controlled trial was conducted in a total of 34 enrolled subjects. The subjects were randomly assigned to the AP-containing dietary supplement (AP supplement; in a daily dose of 250 mg as AP; n=17) or placebo (n=17) and the intervention was continued for 8 weeks. Prior to the start of the intervention (baseline) and after 4 and 8 weeks of intervention, plasma glucose and insulin were measured during a two-hour OGTT. Compared with the baseline, plasma glucose and insulin levels at 90 and/or 120 min, as well as the total area under the curve values during the OGTT (AUC0→2h) for glucose and insulin, were significantly reduced in the AP group, but not in the placebo group after intervention for 8 weeks. The decline from baseline in plasma glucose and insulin at 90 or 120 min of the OGTT for the AP group was significantly greater compared with that of the placebo group after 8 weeks of intervention. No AP supplement-related adverse side-effects nor any abnormal changes in routine laboratory tests and anthropometric parameters were observed throughout the study period. The AP supplement may have the potential to improve glucose homeostasis in subjects with IGT.

Changes in visceral adiposity and serum cholesterol with a novel viscous polysaccharide in Japanese adults with abdominal obesity.

OBJECTIVE: Evidence supports the role of dietary fiber in improving metabolic health. PolyGlycopleX (PGX), a viscous functional polysaccharide improves lipidemia and glycemia in healthy adults. Our objective was to examine the effects of PGX on risk factors associated with the metabolic syndrome in Japanese adults with abdominal obesity. DESIGN AND METHODS: Sixty four subjects assigned to 14 weeks of 15 g day(-1) of PGX or placebo were assessed in a randomized, double-blind, placebo-controlled, parallel group trial. At week 0 and 14, primary outcome measures were serum lipids, abdominal adiposity, glucose tolerance and blood pressure. RESULTS: Total and LDL cholesterol were reduced at week 14 with PGX but not placebo (P < 0.05). The reduction in waist circumference at week 14 was greater with PGX versus placebo (P < 0.05). In females, abdominal visceral fat was decreased to a greater extent with PGX versus placebo (P < 0.05). While glucose tolerance worsened with placebo over time, PGX reduced glucose total area under the curve from week 0 to 6 (P = 0.039). Serum concentrations of resistin and IL6 increased slightly in placebo and decreased slightly with PGX . CONCLUSIONS: PGX is a functional fiber that shows promise in reducing risk factors related to the metabolic syndrome in Japanese adults with abdominal obesity.

Effect of a traditional Japanese garlic preparation on blood pressure in prehypertensive and mildly hypertensive adults.

Numerous clinical studies have used differing garlic preparations leading to controversial results with regard to the hypotensive effect of garlic. This randomized, double-blind, placebo-controlled study was designed to determine the effect of a traditional Japanese garlic homogenate-based supplementary diet (GH diet) product on blood pressure (BP) in subjects with prehypertension and in those with mild hypertension. In total, 34 eligible subjects with prehypertension and 47 with mild hypertension were treated with a daily dose of GH diet (300 mg as dried garlic homogenate; n=16 and 23, respectively) or placebo (n=18 and 24, respectively) for 12 weeks. Of these, 32 prehypertensive subjects (15 on the GH diet and 17 on the placebo) and 40 mildly hypertensive subjects (19 on the GH diet and 21 on the placebo) completed the study and were subjected to efficacy analyses. Systolic and diastolic BPs were monitored at weeks 4, 8 and 12 during the treatment and at post-week 4 following the termination of the treatment. The GH diet induced significant reductions of systolic BP (of between 6.6 and 7.5 mmHg) and diastolic BP (of between 4.6 and 5.2 mmHg) compared with the placebo subsequent to 8 and 12 weeks of treatment. A 12-week intake of the GH diet did not cause any clinically problematic side-effects. We conclude that the GH diet was well tolerated, and had a clinically relevant hypotensive effect in adults with mild hypertension, but not in those with prehypertension.

Evaluation of the effect of a chicken comb extract-containing supplement on cartilage and bone metabolism in athletes.

In a previous study, we revealed that a commercially available product of dietary supplement containing a chicken comb extract (CCE), which is rich in hyaluronan, not only relieves joint pain and other symptoms, but also potentially improves the balance of type II collagen degradation/synthesis in patients with knee osteoarthritis. Since soccer is one of the sports most likely to cause knee osteoarthritis (OA), we evaluated the effect of a CCE-containing supplement on cartilage and bone metabolism in athletes. Fourteen and 15 subjects (all midfielders) were randomly assigned to receive the test product (test group) and the dummy placebo containing only vehicle (placebo group), respectively, for 12 weeks. The daily oral intake of the CCE-containing test product clearly decreased the urinary levels of both C-terminal crosslinked telopeptides of cartilage-specific type II collagen (CTX-II) as a type II collagen degradation marker and the N-terminal telopeptides of bone-specific type I collagen (NTx) as a marker of bone resorption at 12 weeks after the initiation of the intervention. By contrast, no significant reduction was detected in the placebo group at any timepoint during the intervention. These observations indicate that the test product is effective in inhibiting, not only cartilage degradation, but also bone remodeling. Thus, the CCE-containing supplement may be useful for the management of joint health in athletes.

Effect of a chicken comb extract-containing supplement on subclinical joint pain in collegiate soccer players.

Much of our focus of attention has been on sub-clinical or subtle joint pain experienced by healthy soccer players. The present study aimed to determine at which joint such subclinical pains are the most prominent, and to examine the pain-relieving effect of a chicken comb extract (CCE)-containing supplement product (test product) on these athletes. A total of 46 collegiate soccer players, consisting of 24 leading and 22 substitute players, belonging to a university soccer team were enrolled for measuring the pains at 4 different joints (ankle, knee, hip and shoulder) using 3 pain subscales of a 100-mm visual analog scale (VAS) ('pain at rest', 'pain on pressing' and 'pain on moving'), and participated in a prospective, double-blind, controlled study. A total of 23 subjects each received the test product (4,800 mg/day) (test group) and placebo (placebo group) for 12 weeks. VAS pain scores of individual joints were evaluated at baseline and following 4, 8 and 12 weeks of the intervention. VAS scores for the 'pain on moving' subscale in 46 enrolled subjects were highest at the ankle joint, and thus the values (abbreviated as 'pain scores') were used as a parameter for efficacy assessment of the test product. Compared to the baseline, the pain scores were significantly decreased for the dominant foot (but not for the non-dominant foot) in the total subpopulation (at week 4; p<0.01) and the leading player subpopulation (at week 4; p<0.01 and at week 12; p<0.05) in the test group (n=19 and 11, respectively). In comparison between the test product and placebo groups, the pain scores were significantly changed for the dominant foot (p<0.05) at week 4 in the total subpopulation and at week 12 in the leading player subpopulation in the test group. Thus, subclinical joint pain is most prominently observed at the ankle joint of the dominant foot in healthy young soccer players and may be improved by the daily intake of the CCE-containing supplement.

Short-term therapy with luliconazole, a novel topical antifungal imidazole, in guinea pig models of tinea corporis and tinea pedis.

Luliconazole is a novel topical antifungal imidazole with broad-spectrum and potent antifungal activity. The drug is under clinical development in the United States for management of dermatophytosis with a short-term treatment regimen. The present study was undertaken to investigate the clinical benefit of short-term therapy with luliconazole cream in guinea pig models of tinea corporis and tinea pedis induced with Trichophyton mentagrophytes. The dose-dependent therapeutic efficacy of topical luliconazole cream (0.02 to 1%), measured by macroscopic improvement of skin lesions and by fungal eradication as determined by a culture assay, was demonstrated using a tinea corporis model. The improvement in skin lesions seen with luliconazole cream was observed even at a concentration of 0.02%, and its efficacy at 0.1% was equal to that of 1% bifonazole cream. The efficacy of short-term therapy with 1% luliconazole cream, which is used for clinical management, was investigated using the tinea corporis model (4- and 8-day treatment regimens) and the tinea pedis model (7- and 14-day treatment regimens). The 1% luliconazole cream completely eradicated the fungus in half or less of the treatment time required for 1% terbinafine cream and 1% bifonazole cream, as determined by a culture assay for both models. These results clearly indicate that 1% luliconazole cream is sufficiently potent for short-term treatment for dermatophytosis compared to existing drugs. Luliconazole is expected to be useful in the clinical management of dermatophytosis.

Correlation between serum thymus and activation-regulated chemokine levels and stratum corneum barrier function in healthy individuals and patients with mild atopic dermatitis.

BACKGROUND: Serum thymus and activation-regulated chemokine (TARC) levels closely reflect the disease activity of atopic dermatitis (AD). AD is characterized by impaired epidermal barrier function and atopic dry skin. However, dry skin is also a very common problem in healthy individuals. OBJECTIVE: To investigate the relationship between serum TARC levels and epidermal barrier function in healthy subjects and patients with mild AD. METHODS: This study included 2 groups, 121 healthy subjects (healthy group) and 66 patients with mild AD (mild AD group). Barrier function was assessed by transepidermal water loss (TEWL) and stratum corneum hydration (SCH). RESULTS: Significantly elevated serum TARC levels and TEWL values and significantly decreased SCH values were detected in the mild AD group compared to those in the healthy group. In the mild AD group, serum TARC levels were significantly correlated with TEWL values and were inversely correlated with SCH values. Importantly, serum TARC levels were also inversely correlated with SCH values in the healthy controls. TEWL values in the healthy group tended to be correlated with TARC levels but did not reach statistical significance. CONCLUSION: Together with TEWL and SCH, serum TARC level is a useful biomarker, reflecting impairment of epidermal function in AD patients as well as healthy subjects.

Effect of a dietary supplement containing glucosamine hydrochloride, chondroitin sulfate and quercetin glycosides on symptomatic knee osteoarthritis: a randomized, double-blind, placebo-controlled study.

BACKGROUND: Oral glucosamine and chondroitin sulfate, alone and in combination, have been used worldwide for the treatment of osteoarthritis (OA), but their efficacy is controversial. This clinical study was aimed at investigating the potential of a dietary supplement containing glucosamine and chondroitin sulfate in combination with derivatives of quercetin, a naturally occurring flavonoid, (GCQ supplement) for knee OA care. RESULTS: A randomized, double-blind, placebo-controlled study was conducted in 40 Japanese subjects with symptomatic knee OA. Subjects were randomly assigned to GCQ supplement (1200 mg glucosamine hydrochloride, 60 mg chondroitin sulfate and 45 mg quercetin glycosides per day) or placebo and the treatment and follow-up were continued for 16 weeks. The results of symptomatic efficacy assessment based on Japanese Orthopaedic Association criteria showed that scores for two of the four symptom/function subscales, as well as the aggregate scores, were significantly improved at week 16 or earlier in the GCQ group compared to the placebo group. Moreover, analyses of cartilage metabolism biomarkers showed a trend of improvement in type II collagen synthesis/degradation balance in the GCQ group during follow-up. CONCLUSION: GCQ supplement was thought to be more effective than placebo in decreasing the intensity of knee OA-associated clinical symptoms.

Relationships between biomarkers of cartilage, bone, synovial metabolism and knee pain provide insights into the origins of pain in early knee osteoarthritis.

INTRODUCTION: We tested the hypothesis that there exist relationships between the onset of early stage radiographically defined knee osteoarthritis (OA), pain and changes in biomarkers of joint metabolism. METHODS: Using Kellgren-Lawrence (K/L) grading early radiographic knee OA (K/L 2) was detected in 16 of 46 patients. These grades (K/L 1 is no OA and K/L 2 is early OA) were divided into two groups according to the presence or absence of persistent knee pain. Sera (s) and urines (u) were analysed with biomarkers for cartilage collagen cleavage (sC2C and uCTX-II) and synthesis (sCPII), bone resorption (uNTx) and synovitis (hyaluronic acid: sHA). RESULTS: sCPII decreased and sC2C/sCPII, uCTX-II/sCPII and sHA increased with onset of OA (K/L 2 versus K/L 1) irrespective of joint pain. In contrast, sC2C and uCTX-II remained unchanged in early OA patients. Of the patients with K/L grades 1 and 2 sC2C, sCPII, sHA, uNTX and uCTX-II were all significantly increased in patients with knee pain independent of grade. Among the K/L grade 2 subjects, only uCTX-II and uCTX-II/sCPII were increased in those with knee pain. In grade 1 patients both sC2C and sCPII were increased in those with knee pain. No such grade specific changes were seen for the other biomarkers including sHA. CONCLUSIONS: These results suggest that changes in cartilage matrix turnover detected by molecular biomarkers may reflect early changes in cartilage structure that account directly or indirectly for knee pain. Also K/L grade 1 patients with knee pain exhibit biomarker features of early OA.

Beneficial effect of a diet containing heat-killed Lactobacillus paracasei K71 on adult type atopic dermatitis.

The purpose of this study was to investigate the clinical effect of a supplementary diet containing heat-killed lactic acid bacterium Lactobacillus paracasei K71 (LAB diet) on adult patients with atopic dermatitis (AD). A randomized, double-blind, placebo-controlled study was conducted in 34 adult type AD subjects who were treated with conventional topical corticosteroid and tacrolimus. LAB diet or placebo was added over 12 weeks. The primary end-point was the clinical severity of AD which was evaluated by a severity scoring system proposed by the guideline of the Japanese Dermatological Association. The effect was also secondarily evaluated by itch scores of visual analog scales (VAS), quality-of-life (QOL) impairment scores of Skindex 16 and consumption amounts of topical therapeutics. Data on these four assessment variables were collected at baseline and at week 4, 8 and 12. Within the study population, the skin severity scores were significantly decreased from baseline at week 8 (P<0.05) and at week 12 (P<0.01) in the LAB diet group but not in the placebo group. Influence of LAB diet on itch scores or QOL impairment scores was not evident. The consumption of topical therapeutics in the placebo group was 1.9-times greater in total amount compared with the corresponding value in the LAB diet group during the intervention period, although there was no significant difference. No LAB diet- or placebo-related adverse events were observed. We concluded that the LAB diet may have some benefits as a complementary therapy for adult AD patients who are managed with the conventional treatment.