Heterogeneity of treatment effect of vilobelimab in COVID-19: a secondary analysis of a randomised controlled trial.

In a phase 3 trial (PANAMO, NCT04333420), vilobelimab, a complement 5a (C5a) inhibitor, reduced 28-day mortality in mechanically ventilated COVID-19 patients. This post hoc analysis of 368 patients aimed to explore treatment heterogeneity through unsupervised learning. All available clinical variables at baseline were used as input.

Pharmacokinetic analysis of vilobelimab, anaphylatoxin C5a and antidrug antibodies in PANAMO: a phase 3 study in critically ill, invasively mechanically ventilated COVID-19 patients.

Background: Vilobelimab, a complement 5a (C5a)-specific monoclonal antibody, reduced mortality in critically ill COVID-19 patients in a phase 3 multicentre, randomized, double-blind, placebo-controlled study. As part of the study, vilobelimab concentrations and C5a levels as well as antidrug antibodies (ADAs) to vilobelimab were analysed.

Results: From Oct 1, 2020 to Oct 4, 2021, 368 invasively mechanically ventilated COVID-19 patients were randomized: 177 patients were randomly assigned to receive vilobelimab while 191 patients received placebo.

Open-Label Crossover Oral Bioequivalence Pharmacokinetics Comparison for a 3-Day Loading Dose Regimen and 15-Day Steady-State Administration of SUBA-Itraconazole and Conventional Itraconazole Capsules in Healthy Adults.

Super bioavailability (SUBA) itraconazole (S-ITZ), which releases drug in the duodenum, and conventional itraconazole (C-ITZ), which releases drug in the stomach, were compared in two pharmacokinetic (PK) studies: a 3-day loading dose study and a 15-day steady-state administration study. These were crossover oral bioequivalence studies performed under fed conditions in healthy adult volunteers. In the loading dose study, C-ITZ (two doses of 100 mg each) and S-ITZ (two doses of 65 mg each) were administered three times daily for 3 days and once on day 4 ( = 15).

Therapeutic food claims: a global perspective.

Purpose Of Review: Medical foods in the United States, and foods for special medical purposes in other countries, are food formulations used to manage specific chronic diseases or conditions under medical or physician supervision. The process of reviewing and approving food claims for health benefits varies widely from country to country.

Recent Findings: CODEX Alimentarius, a 187-country and one-member (European Union) organization, has standardized not only nutrition labeling and food safety worldwide but has also recently taken on a prominent role in analyzing therapeutic and health claims for food in member countries by providing a framework to study these issues.

Corrigendum to "Clinical and Preclinical Cognitive Function Improvement after Oral Treatment of a Botanical Composition Composed of Extracts from and ".

[This corrects the article DOI: 10.1155/2016/7240802.].

Impact of serum-derived bovine immunoglobulin/protein isolate therapy on irritable bowel syndrome and inflammatory bowel disease: a survey of patient perspective.

Background: Patients with irritable bowel syndrome (IBS) or inflammatory bowel disease (IBD) commonly experience diarrhea, abdominal pain, bloating, and urgency. These symptoms significantly compromise the patient's quality of life (QoL) by limiting participation in normal daily activities and adversely affect work productivity and performance.

Purpose: The aim of this study was to understand from the patient's perspective how oral serum-derived bovine immunoglobulin/protein isolate (SBI) impacts bowel habits, management of condition, and basic QoL.

Clinical and Preclinical Cognitive Function Improvement after Oral Treatment of a Botanical Composition Composed of Extracts from and .

Dementia and cognitive impairment have become the major concerns worldwide due to a significantly aging population, increasing life span and lack of effective pharmacotherapy. In light of limited pharmaceutical drug choices and the socioeconomic implications of these conditions, the search for safe and effective alternatives from natural sources has gained many attractions within the medical food and dietary supplement industry. Two polyphenol extracts derived from roots of and heartwoods of containing free-B-ring flavonoids and flavans, respectively, were combined into a proprietary blend called UP326.

Management of inflammatory bowel disease with oral serum-derived bovine immunoglobulin.

Introduction: The clinical effect of oral serum-derived bovine immunoglobulin/protein isolate (SBI) on symptom and disease management in patients with inflammatory bowel disease (IBD) is reported in this retrospective case series.

Methods: A single-center, retrospective chart review of IBD patients [N = 45; Crohn's disease (CD), n = 38 and ulcerative colitis (UC), n = 7] with limited to no response to traditional pharmaceutical therapies in controlling symptoms was performed after providing SBI (5 g/day) for nutritional support. Patients were contacted at least monthly to assess response to SBI for symptom management measured by a Likert scale (0 = none; 1 = minimal; 2 = moderate; 3 = significant; 4 = complete).

Survival and digestibility of orally-administered immunoglobulin preparations containing IgG through the gastrointestinal tract in humans.

Oral immunoglobulin (Ig) preparations are prime examples of medicinal nutrition from natural sources. Plasma products containing Ig have been used for decades in animal feed for intestinal disorders to mitigate the damaging effects of early weaning. These preparations reduce overall mortality and increase feed utilization in various animal species leading to improved growth.

Management of Loose, Frequent Stools and Fecal Incontinence in a Chronic Mesenteric Ischemia Patient with Oral Serum-derived Bovine Immunoglobulin.

Aim: Chronic diarrhea with fecal incontinence (FI) is a severe, underreported, and intractable problem in many patients for which limited pharmaceutical options exist.

Methods: A retrospective case history was collected after the administration of a prescription medical food composed of serum-derived bovine immunoglobulin/protein isolate (SBI) at 5 g once daily in a patient with chronic mesenteric ischemia (CMI) for chronic loose, frequent, and urgent stools. The patient was an 84-year-old white male with a 20-year history of progressively worsening chronic diarrhea with six to eight watery stools per day (Bristol Stool Form Scale, Type 7), urgency, nocturnal diarrhea, FI, and postprandial abdominal discomfort before administration of SBI.

Bovine immunoglobulin protein isolates for the nutritional management of enteropathy.

The gastrointestinal tract is responsible for a multitude of digestive and immune functions which depend upon the balanced interaction of the intestinal microbiota, diet, gut barrier function, and mucosal immune response. Disruptions in one or more of these factors can lead to intestinal disorders or enteropathies which are characterized by intestinal inflammation, increased gut permeability, and reduced capacity to absorb nutrients. Enteropathy is frequently associated with human immunodeficiency virus (HIV) infection, inflammatory bowel disease, autoimmune enteropathy, radiation enteritis, and irritable bowel syndrome (IBS), where pathologic changes in the intestinal tract lead to abdominal discomfort, bloating, abnormal bowel function (e.

Dietary requirement for serum-derived bovine immunoglobulins in the clinical management of patients with enteropathy.

A variety of human disease conditions are associated with chronic intestinal disorders or enteropathies that are characterized by intestinal inflammation, increased gut permeability, and reduced capacity to absorb nutrients. Such disruptions in the homeostasis of the gastrointestinal (GI) tract can lead to symptoms of abdominal pain and discomfort, bloating, abnormal bowel function, and malabsorption of nutrients. While significant advances have been made in understanding the factors that influence the complex and fragile balance between the gut microbiota, intestinal epithelial cell integrity, and the underlying immune system, effective therapies for restoring intestinal balance during enteropathy are still not available.

Genistein in the metabolic syndrome: results of a randomized clinical trial.

Context: This study was performed to evaluate the effects of genistein on metabolic and cardiovascular risk factors in Caucasian postmenopausal subjects with metabolic syndrome (MetS).

Objective: Our objective was to assess the effects of genistein on surrogate endpoints associated with diabetes and cardiovascular disease.

Design And Setting: This was a randomized, double-blind, placebo-controlled trial at 3 university medical centers in Italy.

The steady-state serum concentration of genistein aglycone is affected by formulation: a bioequivalence study of bone products.

An FDA-regulated, prescription medical food (Fosteum; 27 mg natural genistein, 200 IU cholecalciferol, 20 mg citrated zinc bisglycinate (4 mg elemental zinc) per capsule) and an over-the-counter (OTC) supplement (Citracal Plus Bone Density Builder; 27 mg synthetic genistein, 600 mg elemental calcium (calcium citrate), 400 IU vitamin D3, 50 mg magnesium, 7.5 mg zinc, 1 mg copper, 75 μ g molybdenum, 250 μ g boron per two tablets) were compared to a clinically proven bone formulation (27 mg natural genistein, 400 IU cholecalciferol, 500 mg elemental calcium (calcium carbonate) per tablet; the Squadrito formulation) in an 8-day steady-state pharmacokinetic (PK) study of healthy postmenopausal women (n = 30) randomized to receive 54 mg of genistein per day. Trough serum samples were obtained before the final dose on the morning of the ninth day followed by sampling at 1, 2, 4, 6, 8, 10, 12, 24, 36, 48, 72, and 96 hrs.

5-Lipoxygenase metabolic contributions to NSAID-induced organ toxicity.

Cyclooxygenase (COX)-1, COX-2, and 5-lipoxygenase (5-LOX) enzymes produce effectors of pain and inflammation in osteoarthritis (OA) and many other diseases. All three enzymes play a key role in the metabolism of arachidonic acid (AA) to inflammatory fatty acids, which contribute to the deterioration of cartilage. AA is derived from both phospholipase A(2) (PLA(2)) conversion of cell membrane phospholipids and dietary consumption of omega-6 fatty acids.

Evaluation of CYP450 inhibitory effects and steady-state pharmacokinetics of genistein in combination with cholecalciferol and citrated zinc bisglycinate in postmenopausal women.

Background: The combination of genistein 27 mg, cholecalciferol 200 IU, citrated zinc bisglycinate (4 mg elemental zinc) 20 mg per capsule in Fosteum(®), a prescription medical food regulated by the FDA and indicated for the dietary management of osteopenia and osteoporosis, was tested for drug interactions and to determine the pharmacokinetic profile for genistein, the principal bone-modulating ingredient in the product.

Methods: In vitro human liver microsome cytochrome P450 (CYP450) assays were used to test the product for potential drug interactions with the isoforms 1A2, 2C8, 2C9, 2C19, 2D6, and 3A4. Due to specific 2C8 and 2C9 inhibition, a steady-state pharmacokinetic study was performed to assess serum genistein concentrations by high-pressure liquid chromatography-coupled mass spectroscopy in healthy fasting (n = 10) and fed (n = 10) postmenopausal women.

Flavocoxid inhibits phospholipase A2, peroxidase moieties of the cyclooxygenases (COX), and 5-lipoxygenase, modifies COX-2 gene expression, and acts as an antioxidant.

The multiple mechanisms of action for flavocoxid relating to arachidonic acid (AA) formation and metabolism were studied in vitro. Flavocoxid titrated into rat peritoneal macrophage cultures inhibited cellular phospholipase A2 (PLA(2)) (IC(50) = 60 μg/mL). In in vitro enzyme assays, flavocoxid showed little anti-cyclooxygenase (CO) activity on COX-1/-2 enzymes, but inhibited the COX-1 (IC(50) = 12.

Efficacy and safety of flavocoxid, a novel therapeutic, compared with naproxen: a randomized multicenter controlled trial in subjects with osteoarthritis of the knee.

Introduction: Flavocoxid is a novel flavonoid-based "dual inhibitor" of the 5-lipoxygenase (5-LOX) enzyme and the cyclooxygenase (COX) enzymes. This study was designed to compare the effectiveness and safety of flavocoxid to naproxen in subjects with moderate to severe osteoarthritis (OA) of the knee.

Methods: In this randomized, multicenter, double-blind study, 220 subjects were assigned to receive either flavocoxid (500 mg twice daily) or naproxen (500 mg twice daily) for 12 weeks.

Flavocoxid, an anti-inflammatory agent of botanical origin, does not affect coagulation or interact with anticoagulation therapies.

Introduction: Flavocoxid, a botanical, anti-inflammatory agent, nonspecifically inhibits the peroxidase activity of cyclooxygenase (COX-1 and COX-2) enzymes and 5-lipooxygenase (5-LOX). Due to the concomitant use of aspirin or warfarin in many osteoarthritis (OA) patients with increased cardiovascular risk, we felt it necessary to assess the anticoagulation properties of flavocoxid.

Methods: Three different studies were used: 1) a mouse model to assess effects on bleeding times when combined with aspirin; 2) the effect on platelet function as evaluated by platelet aggregation and bleed times in healthy human subjects; and 3) the effect on international normalized ratio in previously warfarinized patients with OA.

GOAL: multicenter, open-label, post-marketing study of flavocoxid, a novel dual pathway inhibitor anti-inflammatory agent of botanical origin.

Objectives: GOAL (Gauging Osteoarthritis [OA] with Limbrel*), an open-label, post-marketing study was performed to determine the overall efficacy and gastrointestinal (GI) tolerability of flavocoxid, a novel, plant-based, anti-inflammatory medication, in a 'real world' clinical practice setting. To this end, the study enrolled several unique patient types including nonsteroidal anti-inflammatory drug (NSAID) naïve patients, those who had used NSAIDs in the past, regardless of outcome (positive or negative), and those who had previously taken a gastroprotective medication to improve GI tolerability or continued to take it as a precautionary measure to prevent NSAID-associated GI damage.

Methods: A total of 1067 individuals at 41 rheumatology practices were enrolled and prescribed flavocoxid, 500 mg b.

The effect of genistein aglycone on cancer and cancer risk: a review of in vitro, preclinical, and clinical studies.

In Asian epidemiological studies, health benefits, including reduced incidence of breast and prostate cancers, are attributed to soy food and isoflavone consumption. The recent increased intake of soy foods and supplements in the American diet has raised concerns about the possible estrogen-like effects of natural isoflavones and possible promotion or propagation of estrogen-sensitive cancers. These concerns are primarily based on in vitro and rodent data which suggest that genistein aglycone can stimulate tumor cell proliferation and growth in mice having deficient immune systems.

Flavocoxid is as effective as naproxen for managing the signs and symptoms of osteoarthritis of the knee in humans: a short-term randomized, double-blind pilot study.

Flavocoxid (Limbrel), a proprietary mixture of flavonoid molecules (baicalin and catechin), was tested against a traditional nonsteroidal anti-inflammatory drug, naproxen, for the management of the signs and symptoms of moderate osteoarthritis (OA) in humans. Discomfort and global disease activity were used as the primary end points, and safety assessments were also taken for both treatments as a secondary endpoint. In this double-blind study, 103 subjects were randomly assigned to receive either flavocoxid [500 mg twice daily (BID)] or naproxen (500 mg BID) in a 1-month onset of action trial.

Antimicrobial activity of iodoquinol 1%-hydrocortisone acetate 2% gel against ciclopirox and clotrimazole.

Commercially available topical formulations consisting of iodoquinol 1%-hydrocortisone acetate 2%, ciclopirox 0.77%, and clotrimazole 1%-betamethasone dipropionate 0.5% were assessed for their antimicrobial activity against cultures of Micrococcus luteus, Propionibacterium acnes, methicillin-resistant Staphylococcus aureus (MRSA), Pseudomonas aeruginosa, Corynebacterium aquaticum, Trichophyton mentagrophytes, Malassezia furfur, Microsporum canis, Candida albicans, Trichophyton rubrum, or Epidermophyton floccosum.

Breast safety and efficacy of genistein aglycone for postmenopausal bone loss: a follow-up study.

Context: Genistein aglycone improves bone metabolism in women. However, questions about the long-term safety of genistein on breast as well as its continued efficacy still remain.

Objective: We assessed the continued safety profile of genistein aglycone on breast and endometrium and its effects on bone after 3 yr of therapy.