Dimorphic Fungal Coinfection as a Cause of Chronic Diarrhea and Pancolitis

Histoplasma capsulatum and Paracoccidioides brasiliensis are dimorphic fungi that cause systemic mycosis mostly in tropical South America and some areas of North America. Gastrointestinal involvement is not uncommon among these fungal diseases, but coinfection has not previously been reported. We report a patient with chronic diarrhea and pancolitis caused by paracoccidioidomycosis and histoplasmosis

Chronic Diarrhea and Pancolitis Caused by Paracoccidioidomycosis: A Case Report

South American blastomycosis is a systemic micosis caused by infection with Paracoccidioides brasiliensis. The most frequently affected sites are the lower lip buccal mucous membrane, palate, tongue, sublingual region, lymph glands, and lungs. However, colonic involvement is not a common expression of Paracoccidioidomycosis. We report a case of chronic diarrhea and pancolitis caused by Paracoccidioidomycosis with fatal outcome

Effect of a Herbal-Leucine mix on the IL-1β-induced cartilage degradation and inflammatory gene expression in human chondrocytes

<p>Abstract</p> <p>Background</p> <p>Conventional treatments for the articular diseases are often effective for symptom relief, but can also cause significant side effects and do not slow the progression of the disease. Several natural substances have been shown to be effective at relieving the symptoms of osteoarthritis (OA), and preliminary evidence suggests that some of these compounds may exert a favorable influence on the course of the disease. The objective of this study was to investigate the anti-inflammatory/chondroprotective potential of a Herbal and amino acid mixture containing extract of the <it>Uncaria </it>tomentosa, <it>Boswellia spp</it>., <it>Lepidium meyenii and L-Leucine </it>on the IL-1β-induced production of nitric oxide (NO), glycosaminoglycan (GAG), matrix metalloproteinases (MMPs), aggrecan (ACAN) and type II collagen (COL2A1) in human OA chondrocytes and OA cartilage explants.</p> <p>Methods</p> <p>Primary OA chondrocytes or OA cartilage explants were pretreated with Herbal-<it>Leucine </it>mixture (HLM, 1-10 μg/ml) and then stimulated with IL-1β (5 ng/ml). Effect of HLM on IL-1β-induced gene expression of iNOS, MMP-9, MMP-13, ACAN and COL2A1 was verified by real time-PCR. Estimation of NO and GAG release in culture supernatant was done using commercially available kits.</p> <p>Results</p> <p>HLM tested in these <it>in vitro </it>studies was found to be an effective anti-inflammatory agent, as evidenced by strong inhibition of iNOS, MMP-9 and MMP-13 expression and NO production in IL-1β-stimulated OA chondrocytes (p < 0.05). Supporting these gene expression results, IL-1β-induced cartilage matrix breakdown, as evidenced by GAG release from cartilage explants, was also significantly blocked (p < 0.05). Moreover, in the presence of herbal-<it>Leucine </it>mixture (HLM) up-regulation of ACAN and COL2A1 expression in IL-1β-stimulated OA chondrocytes was also noted (p < 0.05). The inhibitory effects of HLM were mediated by inhibiting the activation of nuclear factor (NF)-kB in human OA chondrocytes in presence of IL-1β.</p> <p>Conclusion</p> <p>Our data suggests that HLM could be chondroprotective and anti-inflammatory agent in arthritis, switching chondrocyte gene expression from catabolic direction towards anabolic and regenerative, and consequently this approach may be potentially useful as a new adjunct therapeutic/preventive agent for OA or injury recovery.</p

A case-series study to explore the efficacy of foot orthoses in treating first metatarsophalangeal joint pain

Background: First metatarsophalangeal (MTP) joint pain is a common foot complaint which is often considered to be a consequence of altered mechanics. Foot orthoses are often prescribed to reduce 1 stMTP joint pain with the aim of altering dorsiflexion at propulsion. This study explores changes in 1 stMTP joint pain and kinematics following the use of foot orthoses.Methods: The effect of modified, pre-fabricated foot orthoses (X-line ®) were evaluated in thirty-two patients with 1 stMTP joint pain of mechanical origin. The primary outcome was pain measured at baseline and 24 weeks using the pain subscale of the foot function index (FFI). In a small sub-group of patients (n = 9), the relationship between pain and kinematic variables was explored with and without their orthoses, using an electromagnetic motion tracking (EMT) system.Results: A significant reduction in pain was observed between baseline (median = 48 mm) and the 24 week endpoint (median = 14.50 mm, z = -4.88, p &lt; 0.001). In the sub-group analysis, we found no relationship between pain reduction and 1 stMTP joint motion, and no significant differences were found between the 1 stMTP joint maximum dorsiflexion or ankle/subtalar complex maximum eversion, with and without the orthoses.Conclusions: This observational study demonstrated a significant decrease in 1 stMTP joint pain associated with the use of foot orthoses. Change in pain was not shown to be associated with 1 stMTP joint dorsiflexion nor with altered ankle/subtalar complex eversion. Further research into the effect of foot orthoses on foot function is indicated. © 2010 Welsh et al; licensee BioMed Central Ltd

Comparison of glucosamine sulfate and a polyherbal supplement for the relief of osteoarthritis of the knee: a randomized controlled trial [ISRCTN25438351]

<p>Abstract</p> <p>Background</p> <p>The efficacy and safety of a dietary supplement derived from South American botanicals was compared to glucosamine sulfate in osteoarthritis subjects in a Mumbai-based multi-center, randomized, double-blind study.</p> <p>Methods</p> <p>Subjects (n = 95) were screened and randomized to receive glucosamine sulfate (n = 47, 1500 mg/day) or reparagen (n = 48, 1800 mg/day), a polyherbal consisting of 300 mg of vincaria (<it>Uncaria guianensis</it>) and 1500 mg of RNI 249 (<it>Lepidium meyenii</it>) administered orally, twice daily. Primary efficacy variable was response rate based on a 20% improvement in WOMAC pain scores. Additional outcomes were WOMAC scores for pain, stiffness and function, visual analog score (VAS) for pain, with assessments at 1, 2, 4, 6 and 8 weeks. Tolerability, investigator and subject global assessments and rescue medication consumption (paracetamol) were measured together with safety assessments including vital signs and laboratory based assays.</p> <p>Results</p> <p>Subject randomization was effective: age, gender and disease status distribution was similar in both groups. The response rates (20% reduction in WOMAC pain) were substantial for both glucosamine (89%) and reparagen (94%) and supported by investigator and subject assessments. Using related criteria response rates to reparagen were favorable when compared to glucosamine. Compared to baseline both treatments showed significant benefits in WOMAC and VAS outcomes within one week (P < 0.05), with a similar, progressive improvement over the course of the 8 week treatment protocol (45–62% reduction in WOMAC or VAS scores). Tolerability was excellent, no serious adverse events were noted and safety parameters were unchanged. Rescue medication use was significantly lower in the reparagen group (p < 0.01) at each assessment period. Serum IGF-1 levels were unaltered by treatments.</p> <p>Conclusion</p> <p>Both reparagen and glucosamine sulfate produced substantial improvements in pain, stiffness and function in subjects with osteoarthritis. Response rates were high and the safety profile was excellent, with significantly less rescue medication use with reparagen. Reparagen represents a new natural productive alternative in the management of joint health.</p> <p>Trial registration</p> <p>Current Controlled Trials ISRCTN25438351.</p

The chrondoprotective actions of a natural product are associated with the activation of IGF-1 production by human chondrocytes despite the presence of IL-1β

BACKGROUND: Cartilage loss is a hallmark of arthritis and follows activation of catabolic processes concomitant with a disruption of anabolic pathways like insulin-like growth factor 1 (IGF-1). We hypothesized that two natural products of South American origin, would limit cartilage degradation by respectively suppressing catabolism and activating local IGF-1 anabolic pathways. One extract, derived from cat's claw (Uncaria guianensis, vincaria(®)), is a well-described inhibitor of NF-κB. The other extract, derived from the vegetable Lepidium meyenii (RNI 249), possessed an uncertain mechanism of action but with defined ethnomedical applications for fertility and vitality. METHODS: Human cartilage samples were procured from surgical specimens with consent, and were evaluated either as explants or as primary chondrocytes prepared after enzymatic digestion of cartilage matrix. Assessments included IGF-1 gene expression, IGF-1 production (ELISA), cartilage matrix degradation and nitric oxide (NO) production, under basal conditions and in the presence of IL-1β. RESULTS: RNI 249 enhanced basal IGF-1 mRNA levels in human chondrocytes by 2.7 fold, an effect that was further enhanced to 3.8 fold by co-administration with vincaria. Enhanced basal IGF-1 production by RNI 249 alone and together with vincaria, was confirmed in both explants and in primary chondrocytes (P <0.05). As expected, IL-1β exposure completely silenced IGF-1 production by chondrocytes. However, in the presence of IL-1β both RNI 249 and vincaria protected IGF-1 production in an additive manner (P <0.01) with the combination restoring chondrocyte IGF-1 production to normal levels. Cartilage NO production was dramatically enhanced by IL-1β. Both vincaria and RNI 249 partially attenuated NO production in an additive manner (p < 0.05). IL-1β – induced degradation of cartilage matrix was quantified as glycosaminoglycan release. Individually RNI 249 or vincaria, prevented this catabolic action of IL-1β. CONCLUSION: The identification of agents that activate the autocrine production of IGF-1 in cartilage, even in the face of suppressive pro-inflammatory, catabolic cytokines like IL-1β, represents a novel therapeutic approach to cartilage biology. Chondroprotection associated with prevention of the catabolic events and the potential for sustained anabolic activity with this natural product suggests that it holds significant promise in the treatment of debilitating joint diseases

Impact of Prophylactic Hydroxychloroquine on People at High Risk of COVID-19: A Systematic Review and Meta-Analysis

There are no proven prophylactic interventions for COVID-19. We systematically reviewed the efficacy of prophylactic hydroxychloroquine for COVID-19. Studies evaluating hydroxychloroquine for prophylaxis of COVID-19 were searched in several engines until 8 December 2020. Primary outcomes included RT-PCR positivity, COVID-19 infections (positive RT-PCR or compatible COVID-19 symptoms), and all-cause mortality. Random effects meta-analyses were performed for all outcomes. Five randomized controlled trials (RCTs) (n = 5579) and one cohort (n = 106) were included. Placebo was the comparator in four RCTs, and usual care in one RCT. Compared to the controls, five RCTs showed that hydroxychloroquine prophylaxis did not reduce RT-PCR positivity (RR 1.01, 95% CI 0.88–1.16), COVID-19 infection (RR 0.98, 95% CI 0.78–1.22), or all-cause mortality (RR 0.73, 95% CI 0.27–1.99). There were no differences of effects by pre- or post-exposure prophylaxis. Prophylaxis with hydroxychloroquine increased the risk of diarrhea, abdominal pain, or vomiting (RR 4.56, 95% CI 1.58–13.19). There were no effects of hydroxychloroquine on other secondary outcomes. Quality of evidence was low to very low for all outcomes. Hydroxychloroquine was not efficacious as a prophylaxis for COVID-19 infections, defined either as RT-PCR positivity or as a composite of RT-PCR positivity or compatible symptoms. Hydroxychloroquine did not reduce all-cause mortality, clinical worsening, or adverse events

Efficacy and Safety of Hydroxychloroquine for Hospitalized COVID-19 Patients: A Systematic Review and Meta-Analysis

We systematically reviewed the efficacy and safety of hydroxychloroquine as treatment for hospitalized COVID-19. Randomized controlled trials (RCTs) evaluating hydroxychloroquine as treatment for hospitalized COVID-19 patients were searched until 2nd of December 2020. Primary outcomes were all-cause mortality, need of mechanical ventilation, need of non-invasive ventilation, ICU admission and oxygen support at 14 and 30 days. Secondary outcomes were clinical recovery and worsening, discharge, radiological progression of pneumonia, virologic clearance, serious adverse events (SAE) and adverse events. Inverse variance random effects meta-analyses were performed. Thirteen RCTs (n=18,540) were included. Hydroxychloroquine total doses ranged between 2000 and 12,400 mg; treatment durations were from 5 to 16 days and follow up times between 5 and 30 days. Compared to controls, hydroxychloroquine non-significantly increased mortality at 14 days (RR 1.07, 95%CI 0.92–1.25) or 30 days (RR 1.08, 95%CI 1.00–1.16). Hydroxychloroquine did not affect other primary or secondary outcomes, except SAEs that were significantly higher than the control (RR 1.24, 95%CI 1.05–1.46). Eleven RCTs had high or some concerns of bias. Subgroup analyses were consistent with main analyses. Hydroxychloroquine was not efficacious for treating hospitalized COVID-19 patients and caused more severe adverse events. Hydroxychloroquine should not be recommended as treatment for hospitalized COVID-19 patients