Aspirin 15cH has Different Effects on Morphology and Function of Lipopolysaccharide-Challenged RAW 264.7 Macrophages In Vitro Compared to a Pharmacological Dose of Aspirin.

INTRODUCTION: Aspirin is one of the most commonly used drugs worldwide. It is known to present antipyretic, anti-inflammatory and anti-thrombotic actions, making it extremely useful in a wide range of clinical contexts. Interestingly, homeopathically prepared Aspirin 15cH has been found to have a pro-thrombotic effect in rats, raising the hypothesis that Aspirin 15cH could also modulate the activity of inflammatory cells in different pathological processes. OBJECTIVE: Our objective was to assess what effect Aspirin 15cH has on RAW 264.7 macrophages in vitro. METHODS: The effects of Aspirin 15cH on biochemical and morphological activities of lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages were evaluated. These effects were compared with unchallenged macrophages (negative control), untreated LPS-stimulated macrophages, macrophages treated with succussed water (vehicle control), or aspirin 200 µg/mL (pharmacological inhibitor of LPS activity). Cell morphology (adhered cell area and cytoskeleton arrangements), cell viability, toll-like receptor-4 (TLR-4) expression, and the production of nitric oxide, cytokines and intracellular reactive oxygen species were assessed. RESULTS: Aspirin 15cH reduced the number of cells expressing TLR-4 on the surface (p = 0.03) and induced a "columnar" morphology of macrophage pseudopods, indicating changes in cytoskeleton arrangement. When cells were treated with both Aspirin 15cH and LPS, cell morphology became heterogeneous, suggesting that sub-populations of cells had differing sensitivities to LPS or Aspirin 15cH. Exposure of the cells to LPS alone, succussed water or aspirin 200 µg/mL produced effects consistent with the literature. CONCLUSION: Aspirin 15cH, aspirin 200 µg/mL, LPS and succussed water appear to act as independent stimuli able to induce different patterns of macrophage response. Aspirin 15cH induced changes suggestive of M2 polarization of the macrophages (i.e., toward a wound healing or tissue repair, rather than inflammatory, phenotype). These preliminary findings need to be confirmed in further specific studies.

Effects of Ultra-Low-Dose Aspirin in Thrombosis and Haemorrhage.

BACKGROUND: Aspirin is the oldest and possibly the most widely used pharmacologically active substance still used in allopathic medicine. Its effect on fever and inflammation has paved the way to its anti-thrombotic effect. Dilutions of aspirin have been tested for many years in the University of Bordeaux, in humans as well as in animal models. METHODS: This article is a review of the totality of articles published by the Laboratory of Hematology of the Faculty of Pharmacy of the University of Bordeaux, reporting different doses and dilutions of aspirin, different kinds of inhibitors, transgenic mice and animal models of disease such as portal hypertension and cirrhosis. RESULTS: Homeopathic dilutions of aspirin, notably 15 cH, have shown a pro-thrombotic effect in humans and in in-vivo animal studies. Longitudinal studies in rats have also shown an initial anti-thrombotic effect followed by a pro-thrombotic effect of aspirin several days after a single high-dose administration. This pro-thrombotic effect seems to act by inhibiting the cyclooxygenase (COX)-2 pathway in studies performed with COX selective inhibitors and in knock-out mice without COX-1 or COX-2. This effect may explain the thrombo-embolic complications described after aspirin withdrawal for the purposes of surgery or after non-compliance with anti-platelet therapy, and it may be beneficial in normalising primary haemostasis and decreasing haemorrhage in animal models of portal hypertension and cirrhosis. CONCLUSIONS: Aspirin 15 cH acts through the inhibition of the COX-2 pathway producing a clear pro-thrombotic effect. Further studies should clarify if the pro-thrombotic effect of aspirin withdrawal and the effect of aspirin 15 cH are related, as secondary effects of the same drug. Clarifying this last outcome may be of great significance to public health.

Changes in pharmacist's recommendations of over-the-counter treatments for the common cold during the COVID-19 pandemic.

BACKGROUND: The common cold is one of the most frequently occurring illnesses worldwide. The aim of this study was to determine which OTC anti-common cold medications were most often recommended by pharmacists and if the COVID-19 pandemic affected such recommendations. METHODS: Non-interventional, observational research trial using a self-developed questionnaire to collect data on pharmacists' recommendations for anti-common cold OTC treatment. The data were collected during the COVID-19 pandemic (December 2021-February 2022) in four large community network pharmacies in Lodz (Poland) and then compared with an analogue period of time before the pandemic (December 2019-February 2020). RESULTS: During COVID-19 pandemic there was a significant (p < 0.05) reduction in paracetamol, acetylsalicylic acid, metamizole magnesium, inosines, alpha-mimetics, mucolytics, homeopathics, and sore throat products and an increase in other tablets/capsules and add-on product recommendations. There was a significant relationship (p < 0.05, OR > 1) between the recommended frequency of paracetamol, inosines, sore throat products (each symptom), metamizole magnesium (headache, fever), acetylsalicylic acid (headache, fever, fatigue), NSAIDs, alpha-mimetics (headache, rhinorrhea), pseudoephedrine (rhinorrhea), homeopathics (headache), herbal products (fatigue), antihistamines (rhinorrhea, cough), and mucolytics (headache, fever, cough). CONCLUSIONS: Favorable prices (before COVID-19 pandemic) and reports on common NSAIDs side effects (beginning of the pandemic) led to high sale of paracetamol. Increased awareness of clinical effectiveness of some medications or their reduced availability influenced their limited recommendations.

[A short history of anti-rheumatic therapy. I. An introduction on traditional and drug treatments]. / Piccola storia della terapia antireumatica. I. Una premessa sulle terapie tradizionali e farmacologiche.

The origins of anti-rheumatic therapy are very old and mainly related to the use of traditional, sometimes extravagant, treatments, as a part of folk medicine. Spa therapy has long been used for the treatment of rheumatic diseases, as well as, in later times, physical treatments, including electrotherapy. Drug treatment has developed beginning from substances of vegetable origin, such as willow and colchicum extracts. Then it has been spread out through the chemical synthesis of compounds with specific action and therefore more effective, owing to the great development of pharmaceutical industry.

Macrophage activity regulation by high dilution of aspirin and its possible mechanism

Under LPS-stimulus, platelets can activate macrophagesby a cell-to-cell contact or through cytokine degranulation. Rebound effects of anti-thrombotic agents, such as prostanoids and COX inhibitors can lead to thrombosis, infarct, and stroke. Aspirin has been prescribed for decades due to its powerful antiplatelet action, but it is also related to paradoxical effects such as withdrawal syndrome peaks, resistance, and thrombogenesis. Ultra-diluted aspirin can also produce the same effect in one hour, regardless of Cox-2, by still unknown pathways. Antithrombotic effects of aspirin are also reversed by its high dilutions.Aims: This study aims to characterize the effects of aspirin 15cH on macrophages challenged with LPS, a Cox-2 activator.Methodology: RAW 264.7 macrophages were sown in 24 wells plates using R10medium, boosted with 1µg/ml LPS,and treated with aspirin 15 cH and controls. The activity was evaluated after 24 hours. Supernatants were evaluated for cytokines, nitric oxide, and dielectric oscillations, through solvatochromic dyes (Cartwright's method).Results and discussion: macrophage spreading was increased by aspirin 15 cH, anLPS-like effect. Paradoxically, a significant reduction of this effect was noted when both, LPS and aspirin 15 cH, were added. Succussed water reversed the effect of LPS, leading to TNF (p<0.05) production close to baseline levels. Also, the single treatment with succussed water inhibited IL-10 production (p<0.05), but aspirin 200 µg/mL (positive control) highly increased it (p<0.0001), showing the validity of the model. Nitric oxide production was strengthened by LPS presence (p<0.0001), as expected, but partially downregulated after treatment with aspirin 200 µg/mL, water and succussed water. A pilot study with solvatochromic dyes showed no significant difference among treatments.Conclusion: The main data suggest that aspirin 15 cH increases macrophage activity but presents a paradoxal effect when mixed with LPS. On the other hand, succussed water itself has modulatory effects on macrophages.

[The Italian contributions to the history of salicylates]. / Il contributo italiano alla storia dei salicilati.

It is well-known that the modern history of salicylates began in 1899 when the compound acetylsalicylic acid was registered and introduced commercially as "aspirin" by the Bayer Company of Germany. As a matter of fact, however, remedies made from willow bark had been used to treat fever and rheumatic complaints at least since 1763, when Edward Stone described their efficacy against malarian fever. A number of Italian scientists made significant contributions during the long period of research leading up to the synthesis of acetylsalicylic acid and its widespread use in rheumatic diseases. In this paper we will review the contributions of some of these researchers, beginning with Bartolomeo Rigatelli, who in 1824 used a willow bark extract as a therapeutic agent, denominating it "salino amarissimo antifebbrile" (very bitter antipyretic salt). In the same year, Francesco Fontana described this natural compound, giving it the name "salicina" (salicin). Two other Italian chemists added considerably to current knowledge of the salicylates: Raffaele Piria in 1838, while working as a research fellow in Paris, extracted the chemical compound salicylic acid, and Cesare Bertagnini in 1855 published a detailed description of the classic adverse event associated with salicylate overdoses--tinnitus--which he studied by deliberately ingesting excessive doses himself. Bertagnini and above all Piria also played conspicuous roles in the history of Italy during the period of the Italian Risorgimento, participating as volunteers in the crucial battle of Curtatone and Montanara during the first Italian War of Independence.

Aspirin chemoprevention of colorectal and oesophageal cancers. An overview of the literature and homeopathic explanation.

Recent reports in the medical literature indicate that the regular consumption of aspirin reduces the risk of both colorectal and oesophageal cancers. This paper reviews the scientific evidence for and against this suggestion. In extension of the science, a homeopathic basis for protection is proposed. The homeopathic mechanism relates to the ability of aspirin to induce the symptoms suggestive of cancer in these organs. Since homeopathy employs small doses of the mother compound, perhaps low doses of aspirin could be used to reduce the risk of cancer in the general population or in patients with precancerous colorectal and oesophageal lesions. This approach would also help to minimize the risk of adverse aspirin side-effects on the digestive system. Furthermore, in patients with colorectal and oesophageal cancers, high doses of aspirin could be given to concentrate the pharmacological/homeopathic effects.

Hmong folk remedies: limited acetylation of opium by aspirin and acetaminophen.

The traditional folk medicine of the Hmong and other Southeast Asian refugees has accompanied them during their immigration in this country over the past two decades. In two recent cases involving Hmong defendants, unknown solids, resembling charcoal in consistency and purported to be "backache remedies," were analyzed and found to be complex mixtures of aspirin, acetaminophen, caffeine and partly acetylated opium. In particular, significant amounts of acetylacetaminophen, 3-O-acetylmorphine, 6-O-acetylcodeine, 6-O-acetylmorphine, and heroin were identified by gas chromatography/mass spectrometry. Heating approximately equal weights of solid opium, aspirin, and acetaminophen at 130 degrees C for several hours produced a mixture of compounds showing a similar acetylation pattern.

Psychological factors influencing post-operative pain and analgesic consumption.

The personality factors, post-operative pain experience and analgesic requirements after minor oral surgery under general anaesthesia of 103 patients are presented. Psychiatric morbidity, neuroticism and anxiety were related to increased pain which tended to persist longer than normal. Trait anxiety also correlated with simple analgesic consumption, and neuroticism was weakly associated with Omnopon requirements. Thus, regular analgesics prescribed for at least 3 days will anticipate the needs of such patients. Despite higher levels of anxiety and neuroticism, women did not complain of more pain or require more analgesia than men in this study. There was also no overall correlation between post-operative pain experience and analgesic requirements. Therefore analgesic tablet consumption cannot be used as a measure of pain control.

[Remarks on some analgesics used in the pain clinic].

The mechanism of action of aspirin as an analgesic is an inhibition of biosynthesis of prostaglandins. Thus the site of action has been believed to be peripheral. However, when aspirin is injected intra- thecally, it produces an analgesic effect. Aspirin has a membrane-stabilizing effect and it is used locally for the treatment of post- herpetic neuralgia. Epidural opioids are frequently used for the management of post-operative pain or cancer pain. Pharmacokinetic studies have shown that delayed respiratory depression results from migration of morphine in the cerebrospinal fluid to the brain. Peak concentrations of morphine near the brain stem occur about 3 hours after lumbar epidural injection, whereas lipophilic opioids such as meperidine, peak concentration occur within 30 to 60 minutes. The clearance from cerebrospinal fluid of lipophilic opioids is more rapid than that of morphine. Besides opioids, alpha 2 receptor agonists such as clonidine also have analgesic action when administered into the epidural space. Somatostatin is one of many neuropeptides found in the spinal cord. It has dual action: a mediation of thermal nociception and a general antinociceptive action. When somatostatin is administered intrathecally or epidurally, it produces analgesic effect and its efficacy appears to be equal to that of morphine.

Aspirina en dosis ultrabajas y hormesis / Aspirin in ultra-low doses and hormesis

La relación entre hormesis y Homeopatía resulta hoy en día controvertida. Por un lado, sus primeros fundamentos fueron enunciados con el objeto de explicar los efectos de la Homeopatía. Por otro lado, la mayoría de los trabajos realizados que muestran efectos horméticos fueron realizados a concentraciones mucho mayores que las utilizadas en Homeopatía. El presente trabajo muestra varios puntos de contacto entre la Homeopatía y el concepto de hormesis, y muestra la relación que existe entre los trabajos realizados sobre los efectos de la aspirina 15CH y los distintos tipos de hormesis.

Evidence of the principle of similitude in modern fatal iatrogenic events.

Samuel Hahnemann attributed fundamental importance to the principle of similitude, promoting it to a 'natural law'. Observing that enantiopathic or allopathic treatment produced enduring aggravation of the disease symptoms after a brief and transitory initial relief, he systematised homeopathic treatment, prescribing substances that provoke similar symptoms in healthy individual. Based on clinical and experimental observations, he anticipated the concept of homeostasis, dividing the effects of substances into: primary action of the medicine followed by secondary action or reaction of the organism. This reaction, known as the rebound effect or paradoxical action by modern pharmacology, used to awake the curative response of the body when the principle of similitude is applied, is responsible for several iatrogenic diseases when used on the basis of the principle of contraries. This study discusses the role of this paradoxical reaction of the organism in the fatal side effects of four important drugs, used according to the model of enantiopathic treatment of the symptoms. I present evidence relating to acetylsalicylic acid, rofecoxib, antidepressants and long-acting bronchodilators. The consequences of the allopathic treatment could be decreased if health professionals valued homeostasis, minimising the rebound effect of the organism by gradual suspension of palliative drugs.

Comparison of infusions of morphine and lysine acetyl salicylate for the relief of pain following thoracic surgery.

A double-blind study comparing the effectiveness of a continuous infusion i.v. of lysine acetyl salicylate (LAS) with an infusion of morphine for the treatment of pain following pulmonary surgery is described. Mean pain scores in the two groups were not significantly different at any stage during the 24-h period of study. LAS was not associated with any significantly greater blood loss in the period after operation. The incidence of drowsiness, nausea and vomiting, and the need for antiemetic medication were similar in both groups.

[Therapy of common cold with a homeopathic combination preparation in comparison with acetylsalicylic acid. A controlled, randomized double-blind study]. / Therapie des grippalen Infekts mit einem homöopathischen Kombinationspräparat im Vergleich zu Acetylsalicylsäure. Kontrollierte, randomisierte Einfachblindstudie.

A clinical test was carried out on 170 West German army soldiers suffering from common cold. The test was conducted on a monocentric, randomized, non-sequential, and inter-individual basis; the research workers were kept blind on the identity of the medication. The purpose of testing was to compare the effectiveness of a combination homeopathic preparation (Gripp-Heel) with that of acetylsalicylic acid. On the 4th and 10th treatment days, no significant difference was determined with respect to changes in clinical findings, subjectively assessed complaints, or length of time the patients were unable to work. Thus the two preparations possess comparative effectiveness in the treatment of the common cold.

[A controlled clinical trial for testing the efficacy of the homeopathic drug eupatorium perfoliatum D2 inthe treatment of common cold (author's transl)]. / Klinishe Prüfung zum Nachweis der therapeutischen Wirksamkeit des homöopathischen Arzneimittels Eupatorium perfoliatum D 2 (Wasserhanf composite) bei der Diagnose "Grippaler Infekt"1.

53 outpatients suffering from common cold (flu) were randomly assigned to either a therapy with acetylsalicylic acid (ASA) or the homeopathic drug Eupatorium perfoliatum D2 in a controlled clinical trial. The efficacy of the drugs was assessed on day 1, 4 and 10 of the infection by symptom check lists and physical examinations. Neither subjective complaints nor body temperature or laboratory findings showed any significant differences between groups which was taken as evidence that both drugs were equally effective.

Pyrazolones in the treatment of postoperative pain.

The aim pursued in postoperative analgesia is to mobilize patients, to prevent thrombo-embolism, to improve subjective well-being, and to reduce the stress reaction caused by pain. In sufficiently high doses, metamizol is equally as suitable for the treatment of postoperative traumatic pain as are opioids. Comparative studies provide evidence that metamizol is no less potent in its action than pethidine, and that in cases of pain in the head and neck region it is superior to buprenorphine in its usual dose. It can also be used to supplement opioid medication where this does not produce satisfactory analgesia. In patients with a history of drug abuse, metamizol is in fact the drug of choice for immediate postoperative analgesic treatment.

Drug-induced asthma: a review.

A review of clinical and experimental data pertaining to drug-induced asthma is presented. Various drugs and drug additives causing asthma are classified and their possible modes of action in inducing asthma are discussed. Practical recommendations for diagnosis and prevention of drug-induced asthma are enumerated.