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The American Journal of Clinical... May 2007Histamine intolerance results from a disequilibrium of accumulated histamine and the capacity for histamine degradation. Histamine is a biogenic amine that occurs to... (Review)
Review
Histamine intolerance results from a disequilibrium of accumulated histamine and the capacity for histamine degradation. Histamine is a biogenic amine that occurs to various degrees in many foods. In healthy persons, dietary histamine can be rapidly detoxified by amine oxidases, whereas persons with low amine oxidase activity are at risk of histamine toxicity. Diamine oxidase (DAO) is the main enzyme for the metabolism of ingested histamine. It has been proposed that DAO, when functioning as a secretory protein, may be responsible for scavenging extracellular histamine after mediator release. Conversely, histamine N-methyltransferase, the other important enzyme inactivating histamine, is a cytosolic protein that can convert histamine only in the intracellular space of cells. An impaired histamine degradation based on reduced DAO activity and the resulting histamine excess may cause numerous symptoms mimicking an allergic reaction. The ingestion of histamine-rich food or of alcohol or drugs that release histamine or block DAO may provoke diarrhea, headache, rhinoconjunctival symptoms, asthma, hypotension, arrhythmia, urticaria, pruritus, flushing, and other conditions in patients with histamine intolerance. Symptoms can be reduced by a histamine-free diet or be eliminated by antihistamines. However, because of the multifaceted nature of the symptoms, the existence of histamine intolerance has been underestimated, and further studies based on double-blind, placebo-controlled provocations are needed. In patients in whom the abovementioned symptoms are triggered by the corresponding substances and who have a negative diagnosis of allergy or internal disorders, histamine intolerance should be considered as an underlying pathomechanism.
Topics: Amine Oxidase (Copper-Containing); Food Hypersensitivity; Histamine; Histamine Agents; Histamine H1 Antagonists; Histamine N-Methyltransferase; Humans; Hypersensitivity, Delayed; Hypersensitivity, Immediate
PubMed: 17490952
DOI: 10.1093/ajcn/85.5.1185 -
Advances in Nutrition (Bethesda, Md.) Jan 2019The consumption of sugar-free foods is growing because of their low-calorie content and the health concerns about products with high sugar content. Sweeteners that are...
The consumption of sugar-free foods is growing because of their low-calorie content and the health concerns about products with high sugar content. Sweeteners that are frequently several hundred thousand times sweeter than sucrose are being consumed as sugar substitutes. Although nonnutritive sweeteners (NNSs) are considered safe and well tolerated, their effects on glucose intolerance, the activation of sweet taste receptors, and alterations to the composition of the intestinal microbiota are controversial. This review critically discusses the evidence supporting the effects of NNSs, both synthetic sweeteners (acesulfame K, aspartame, cyclamate, saccharin, neotame, advantame, and sucralose) and natural sweeteners (NSs; thaumatin, steviol glucosides, monellin, neohesperidin dihydrochalcone, and glycyrrhizin) and nutritive sweeteners (polyols or sugar alcohols) on the composition of microbiota in the human gut. So far, only saccharin and sucralose (NNSs) and stevia (NS) change the composition of the gut microbiota. By definition, a prebiotic is a nondigestible food ingredient, but some polyols can be absorbed, at least partially, in the small intestine by passive diffusion: however, a number of them, such as isomaltose, maltitol, lactitol, and xylitol, can reach the large bowel and increase the numbers of bifidobacteria in humans. Further research on the effects of sweeteners on the composition of the human gut microbiome is necessary.
PubMed: 30721958
DOI: 10.1093/advances/nmy037 -
The Cochrane Database of Systematic... Jul 2017Pain is a common symptom with cancer, and 30% to 50% of all people with cancer will experience moderate to severe pain that can have a major negative impact on their... (Review)
Review
BACKGROUND
Pain is a common symptom with cancer, and 30% to 50% of all people with cancer will experience moderate to severe pain that can have a major negative impact on their quality of life. Opioid (morphine-like) drugs are commonly used to treat moderate or severe cancer pain, and are recommended for this purpose in the World Health Organization (WHO) pain treatment ladder. The most commonly-used opioid drugs are buprenorphine, codeine, fentanyl, hydrocodone, hydromorphone, methadone, morphine, oxycodone, tramadol, and tapentadol.
OBJECTIVES
To provide an overview of the analgesic efficacy of opioids in cancer pain, and to report on adverse events associated with their use.
METHODS
We identified systematic reviews examining any opioid for cancer pain published to 4 May 2017 in the Cochrane Database of Systematic Reviews in the Cochrane Library. The primary outcomes were no or mild pain within 14 days of starting treatment, withdrawals due to adverse events, and serious adverse events.
MAIN RESULTS
We included nine reviews with 152 included studies and 13,524 participants, but because some studies appeared in more than one review the number of unique studies and participants was smaller than this. Most participants had moderate or severe pain associated with a range of different types of cancer. Studies in the reviews typically compared one type of opioid or formulation with either a different formulation of the same opioid, or a different opioid; few included a placebo control. Typically the reviews titrated dose to effect, a balance between pain relief and adverse events. Various routes of administration of opioids were considered in the reviews; oral with most opioids, but transdermal administration with fentanyl, and buprenorphine. No review included studies of subcutaneous opioid administration. Pain outcomes reported were varied and inconsistent. The average size of included studies varied considerably between reviews: studies of older opioids, such as codeine, morphine, and methadone, had low average study sizes while those involving newer drugs tended to have larger study sizes.Six reviews reported a GRADE assessment (buprenorphine, codeine, hydromorphone, methadone, oxycodone, and tramadol), but not necessarily for all comparisons or outcomes. No comparative analyses were possible because there was no consistent placebo or active control. Cohort outcomes for opioids are therefore reported, as absolute numbers or percentages, or both.Reviews on buprenorphine, codeine with or without paracetamol, hydromorphone, methadone, tramadol with or without paracetamol, tapentadol, and oxycodone did not have information about the primary outcome of mild or no pain at 14 days, although that on oxycodone indicated that average pain scores were within that range. Two reviews, on oral morphine and transdermal fentanyl, reported that 96% of 850 participants achieved that goal.Adverse event withdrawal was reported by five reviews, at rates of between 6% and 19%. Participants with at least one adverse event were reported by three reviews, at rates of between 11% and 77%.Our GRADE assessment of evidence quality was very low for all outcomes, because many studies in the reviews were at high risk of bias from several sources, including small study size.
AUTHORS' CONCLUSIONS
The amount and quality of evidence around the use of opioids for treating cancer pain is disappointingly low, although the evidence we have indicates that around 19 out of 20 people with moderate or severe pain who are given opioids and can tolerate them should have that pain reduced to mild or no pain within 14 days. This accords with the clinical experience in treating many people with cancer pain, but overstates to some extent the effectiveness found for the WHO pain ladder. Most people will experience adverse events, and help may be needed to manage the more common undesirable adverse effects such as constipation and nausea. Perhaps between 1 in 10 and 2 in 10 people treated with opioids will find these adverse events intolerable, leading to a change in treatment.
Topics: Acetaminophen; Administration, Cutaneous; Administration, Oral; Analgesics, Opioid; Buprenorphine; Cancer Pain; Codeine; Fentanyl; Humans; Hydromorphone; Methadone; Oxycodone; Phenols; Review Literature as Topic; Tapentadol; Tramadol
PubMed: 28683172
DOI: 10.1002/14651858.CD012592.pub2 -
Molecules (Basel, Switzerland) Oct 2021Glyceryl trinitrate (GTN) is one of the earliest known treatments for angina with a fascinating history that bridges three centuries. However, despite its central role... (Review)
Review
Glyceryl trinitrate (GTN) is one of the earliest known treatments for angina with a fascinating history that bridges three centuries. However, despite its central role in the nitric oxide (NO) story as a NO-donating compound, establishing the precise mechanism of how GTN exerts its medicinal benefit has proven to be far more difficult. This review brings together the explosive and vasodilatory nature of this three-carbon molecule while providing an update on the likely in vivo pathways through which GTN, and the rest of the organic nitrate family, release NO, nitrite, or a combination of both, while also trying to explain nitrate tolerance. Over the last 20 years the alcohol detoxification enzyme, aldehyde dehydrogenase (ALDH), has undoubtedly emerged as the front runner to explaining GTN's bioactivation. This is best illustrated by reduced GTN efficacy in subjects carrying the single point mutation (Glu504Lys) in ALDH, which is also responsible for alcohol intolerance, as characterized by flushing. While these findings are significant for anyone following the GTN story, they appear particularly relevant for healthcare professionals, and especially so, if administering GTN to patients as an emergency treatment. In short, although the GTN puzzle has not been fully solved, clinical study data continue to cement the importance of ALDH, as uncovered in 2002, as a key GTN activator.
Topics: Alcohol Drinking; Alcoholism; Aldehyde Dehydrogenase; Animals; Humans; Nitroglycerin; Vasodilator Agents
PubMed: 34770988
DOI: 10.3390/molecules26216581 -
Blood Oct 2019Prior studies have reported high response rates with recombinant interferon-α (rIFN-α) therapy in patients with essential thrombocythemia (ET) and polycythemia vera...
Prior studies have reported high response rates with recombinant interferon-α (rIFN-α) therapy in patients with essential thrombocythemia (ET) and polycythemia vera (PV). To further define the role of rIFN-α, we investigated the outcomes of pegylated-rIFN-α2a (PEG) therapy in ET and PV patients previously treated with hydroxyurea (HU). The Myeloproliferative Disorders Research Consortium (MPD-RC)-111 study was an investigator-initiated, international, multicenter, phase 2 trial evaluating the ability of PEG therapy to induce complete (CR) and partial (PR) hematologic responses in patients with high-risk ET or PV who were either refractory or intolerant to HU. The study included 65 patients with ET and 50 patients with PV. The overall response rates (ORRs; CR/PR) at 12 months were 69.2% (43.1% and 26.2%) in ET patients and 60% (22% and 38%) in PV patients. CR rates were higher in CALR-mutated ET patients (56.5% vs 28.0%; P = .01), compared with those in subjects lacking a CALR mutation. The median absolute reduction in JAK2V617F variant allele fraction was -6% (range, -84% to 47%) in patients achieving a CR vs +4% (range, -18% to 56%) in patients with PR or nonresponse (NR). Therapy was associated with a significant rate of adverse events (AEs); most were manageable, and PEG discontinuation related to AEs occurred in only 13.9% of subjects. We conclude that PEG is an effective therapy for patients with ET or PV who were previously refractory and/or intolerant of HU. This trial was registered at www.clinicaltrials.gov as #NCT01259856.
Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Agents; Drug Resistance, Neoplasm; Female; Humans; Hydroxyurea; Interferon-alpha; Male; Middle Aged; Polycythemia Vera; Polyethylene Glycols; Recombinant Proteins; Thrombocythemia, Essential; Treatment Outcome
PubMed: 31515250
DOI: 10.1182/blood.2019000428 -
Nutrients Apr 2024Histamine intolerance is a condition characterized by the accumulation of histamine to a point that exceeds the body's capacity to eliminate it. Researchers have... (Review)
Review
Histamine intolerance is a condition characterized by the accumulation of histamine to a point that exceeds the body's capacity to eliminate it. Researchers have attributed several reasons to this condition, such as genetic factors, alcohol, and dietary deficiencies, among other elements. Symptoms of histamine intolerance have been found to extend beyond the gastrointestinal tract and to the whole body, with these symptoms being sporadic and non-specific. This review will explore various aspects related to histamine intolerance, such as its causes, symptoms, diagnosis, and information related to management.
Topics: Humans; Histamine; Food Intolerance; Food Hypersensitivity
PubMed: 38674909
DOI: 10.3390/nu16081219 -
Cell Feb 2024Carbohydrate intolerance, commonly linked to the consumption of lactose, fructose, or sorbitol, affects up to 30% of the population in high-income countries. Although...
Carbohydrate intolerance, commonly linked to the consumption of lactose, fructose, or sorbitol, affects up to 30% of the population in high-income countries. Although sorbitol intolerance is attributed to malabsorption, the underlying mechanism remains unresolved. Here, we show that a history of antibiotic exposure combined with high fat intake triggered long-lasting sorbitol intolerance in mice by reducing Clostridia abundance, which impaired microbial sorbitol catabolism. The restoration of sorbitol catabolism by inoculation with probiotic Escherichia coli protected mice against sorbitol intolerance but did not restore Clostridia abundance. Inoculation with the butyrate producer Anaerostipes caccae restored a normal Clostridia abundance, which protected mice against sorbitol-induced diarrhea even when the probiotic was cleared. Butyrate restored Clostridia abundance by stimulating epithelial peroxisome proliferator-activated receptor-gamma (PPAR-γ) signaling to restore epithelial hypoxia in the colon. Collectively, these mechanistic insights identify microbial sorbitol catabolism as a potential target for approaches for the diagnosis, treatment, and prevention of sorbitol intolerance.
Topics: Animals; Mice; Anti-Bacterial Agents; Butyrates; Carbohydrate Metabolism, Inborn Errors; Clostridium; Escherichia coli; Gastrointestinal Microbiome; Sorbitol
PubMed: 38366592
DOI: 10.1016/j.cell.2024.01.029 -
Arthritis & Rheumatology (Hoboken, N.J.) Feb 2023To assess efficacy, safety, pharmacokinetics, and immunogenicity of pegloticase plus methotrexate (MTX) versus pegloticase plus placebo cotreatment for uncontrolled gout... (Randomized Controlled Trial)
Randomized Controlled Trial
A Randomized, Placebo-Controlled Study of Methotrexate to Increase Response Rates in Patients with Uncontrolled Gout Receiving Pegloticase: Primary Efficacy and Safety Findings.
OBJECTIVE
To assess efficacy, safety, pharmacokinetics, and immunogenicity of pegloticase plus methotrexate (MTX) versus pegloticase plus placebo cotreatment for uncontrolled gout in a randomized, placebo-controlled, double-blind trial.
METHODS
This study included adults with uncontrolled gout, defined as serum urate ≥7 mg/dl, oral urate-lowering therapy failure or intolerance, and presence of ongoing gout symptoms including ≥1 tophus, ≥2 flares in the past 12 months, or gouty arthritis. Key exclusion criteria included MTX contraindication, current immunosuppressant use, G6PDH deficiency, and estimated glomerular filtration rate <40 ml/minute/1.73 m . Patients were randomized 2:1 to 52 weeks of pegloticase (8 mg biweekly) with either oral MTX (15 mg/week) or placebo. The primary end point was the proportion of treatment responders during month 6 (defined as serum urate <6 mg/dl for ≥80% of visits during weeks 20-24). Efficacy was evaluated in all randomized patients (intent-to-treat population), and safety was evaluated in all patients receiving ≥1 blinded MTX or placebo dose.
RESULTS
A total of 152 patients were randomized, 100 to receive pegloticase plus MTX, 52 to receive pegloticase plus placebo. Significantly higher treatment response occurred during month 6 in the MTX group versus the placebo group (71.0% [71 of 100 patients] versus 38.5% [20 of 52 patients], respectively; between-group difference 32.3% [95% confidence interval 16.3%, 48.3%]) (P < 0.0001 for between-group difference). During the first 6 months of pegloticase plus MTX or pegloticase plus placebo treatment, 78 (81.3%) of 96 MTX patients versus 47 (95.9%) of 49 placebo patients experienced ≥1 adverse event (AE), most commonly gout flare (64 [66.7%] of 96 MTX patients and 34 [69.4%] of 49 placebo patients). Reports of AEs and serious AEs were comparable between groups, but the infusion reaction rate was considerably lower with MTX cotherapy (4.2% [4 of 96 MTX patients, including 1 patient who had anaphylaxis]) than with placebo cotherapy (30.6% [15 of 49 placebo patients, 0 who had anaphylaxis]) (P < 0.001). Antidrug antibody positivity was also lower in the MTX group.
CONCLUSION
MTX cotherapy markedly increased pegloticase response rate over placebo (71.0% versus 38.5%) during month 6 with no new safety signals. These findings verify higher treatment response rate, lower infusion reaction incidence, and lower immunogenicity when pegloticase is coadministered with MTX.
Topics: Adult; Humans; Gout; Methotrexate; Uric Acid; Anaphylaxis; Treatment Outcome; Symptom Flare Up; Gout Suppressants; Arthritis, Gouty; Polyethylene Glycols; Double-Blind Method
PubMed: 36099211
DOI: 10.1002/art.42335 -
Allergologie Select 2018Hypersensitivity reactions to alcoholic beverages (particularly red wine) are relatively frequent, affecting 10% of the general population. Hypersensitivity reactions... (Review)
Review
Hypersensitivity reactions to alcoholic beverages (particularly red wine) are relatively frequent, affecting 10% of the general population. Hypersensitivity reactions due to alcoholic drinks, mainly in the form of airway reactions (rhinitis and asthma), occur significantly more frequently in persons with pre-existing rhinitis and asthma. In terms of pathogenesis, it has to be differentiated between immunologic, mainly IgE-mediated, hypersensitivity reactions (wine allergies), and intolerance reactions in which no causative allergen-specific immune mechanisms can be detected. Allergens responsible for wine allergy could be: grape () proteins (particularly the major allergen lipid transfer protein Vit v1), proteins and ingredients used for the fining of wines such as fish gelatin or isinglass (swim bladder of the fish huso, family of sturgeons), ovalbumin, dairy (casein) products, gum arabic, enzymes (lysozyme, pectinase, glucanase, cellulase, glucosidase, urease, aromatic enzymes), molds (particularly ) responsible for the noble rot in wines, yeasts and proteins from insects that contaminated the mash. Type 1 allergic reactions (positive prick tests) have been described for inorganic components like ethanol, acetaldehyde, acetic acid and sulfites, but no specific IgE could be detected in the serum. Ethanol, acetaldehyde and acetic acid, flavonoids (anthocyanins and chatechines), sulfites, histamine and other biogenic amines are the main causative agents of intolerance reactions (pseudoallergic reactions) to wine. After a short historic review of viticulture and the importance of wine in classical antiquity, we go into the chemical processes of alcoholic fermentation and the genetically inherited "flush syndrome" caused by an acetaldehyde dehydrogenase 2 polymorphism, subsequently we focus on the different etiologic factors of allergies and intolerance reactions to wine. The most frequent intolerance reactions to sulfites occur particularly after the ingestion of white wine and in asthma patients. Intolerance reactions to histamine and other biogenic amines occur mainly after ingestion of red wine and in persons with diamine oxidase (DAO) deficiency.
PubMed: 31826033
DOI: 10.5414/ALX01420E