Nociceptors: a phylogenetic view

The ability to react to environmental change is crucial for the survival of an organism and an essential prerequisite is the capacity to detect and respond to aversive stimuli. The importance of having an inbuilt “detect and protect” system is illustrated by the fact that most animals have dedicated sensory afferents which respond to noxious stimuli called nociceptors. Should injury occur there is often sensitization, whereby increased nociceptor sensitivity and/or plasticity of nociceptor-related neural circuits acts as a protection mechanism for the afflicted body part. Studying nociception and nociceptors in different model organisms has demonstrated that there are similarities from invertebrates right through to humans. The development of technology to genetically manipulate organisms, especially mice, has led to an understanding of some of the key molecular players in nociceptor function. This review will focus on what is known about nociceptors throughout the Animalia kingdom and what similarities exist across phyla; especially at the molecular level of ion channels

How do cardiologists select patients for dual antiplatelet therapy continuation beyond 1 year after a myocardial infarction? Insights from the EYESHOT Post-MI Study

Background: Current guidelines suggest to consider dual antiplatelet therapy (DAPT) continuation for longer than 12 months in selected patients with myocardial infarction (MI). Hypothesis: We sought to assess the criteria used by cardiologists in daily practice to select patients with a history of MI eligible for DAPT continuation beyond 1 year. Methods: We analyzed data from the EYESHOT Post-MI, a prospective, observational, nationwide study aimed to evaluate the management of patients presenting to cardiologists 1 to 3 years from the last MI event. Results: Out of the 1633 post-MI patients enrolled in the study between March and December 2017, 557 (34.1%) were on DAPT at the time of enrolment, and 450 (27.6%) were prescribed DAPT after cardiologist assessment. At multivariate analyses, a percutaneous coronary intervention (PCI) with multiple stents and the presence of peripheral artery disease (PAD) resulted as independent predictors of DAPT continuation, while atrial fibrillation was the only independent predictor of DAPT interruption for patients both at the second and the third year from MI at enrolment and the time of discharge/end of the visit. Conclusions: Risk scores recommended by current guidelines for guiding decisions on DAPT duration are underused and misused in clinical practice. A PCI with multiple stents and a history of PAD resulted as the clinical variables more frequently associated with DAPT continuation beyond 1 year from the index MI

Acute renal failure associated with cocaine and alcohol abuse

A broad spectrum of renal diseases is reported in cocaine abuse subjects, nevertheless the pathogenesis of the acute temporary renal failure is unclear. Cocaine may induce rhabdomyolysis and/or renal vasoconstriction being a powerful sympathomimethic drug and in turn renal failure. A 20-year-old man developed a reversible acute renal failure following an episode of cocaine and alcohol abuse. He was admitted for oliguria, swelling, pain and reduced strength in the left lower limb. The increase of serum creatinine and muscular enzymes and the presence of urinary granular and jaline casts were suggestive of rhabdomyolysis and renal damage. The clinical picture completely recovered after 15 days from the onset. We believe that an intense arterial vasoconstriction was the more probable mechanism of rhabdomyolysis and acute renal failure in this patient both because renal function recovered 5 days after forced diuresis and because biochemical indices of renal activity were always normal during 4 months after hospital discharge. Moreover, the report that the contemporary ingestion of alcohol and cocaine has an additive and synergistic effect causing the hepatic production of cocaethylene, a metabolite able to increase the systemic toxic effects of cocaine, may support our hypothesis

Intracranial hemorrage due to brain metastases in an Italian HCV patient with hepatocellular carcinoma

Brain metastases from hepatocarcinoma are exceptional and only a few cases have been reported in the literature, mainly from Far-Eastern countries. Clinical diagnosis in asymptomatic patients with preserved liver function is difficult and usually late. In some cases, cerebral metastasis is the initial manifestation of HCC and patients may develop intracerebral hemorrage and have a stroke-like presentation. We report on the first Italian case of cerebral metastases from multifocal hepatocellular carcinoma in an asymptomatic HbsAg negative patient with unknown HCV related chronic hepatitis and no evidence of liver cirrhosis. For many years he had a mild liver enzyme elevation and the presence of multiple misinterpreted hypoechogenic hepatic lesions. The hepatic tumor spread to the lungs and the brain and the patient developed two major episodes of intracranial hemorrage. He had two nodular lesions in the brain and alpha-fetoprotein levels were more than 10,000 ng/ml. He died from neurologic causes, without major signs of liver failure

Polymorphonuclear leukocyte-derived o2-reactive species activate platelets in human whole blood.

The activation of human platelets by polymorphonuclear leukocytes (PMN) was investigated in human whole blood challenged with "priming" concentrations of arachidonic acid or collagen in the presence or absence of N-formyl-Met-Leu-Phe (FMLP), a selective activator of PMN. With the use of arachidonic acid or collagen alone at priming concentrations or FMLP alone, no platelet response was observed. In contrast, FMLP in combination with arachidonic acid or collagen caused irreversible platelet aggregation with thromboxane A2 production. Platelet response to FMLP-activated PMN was enhanced by superoxide dismutase and blocked by catalase or the NADPH oxidase inhibitor diphenyliodonium, suggesting a role for the O2-.-H2O2 system in this cellular interaction. This was corroborated by experiments with exogenously added H2O2, which mimicked FMLP effects in the activation of primed platelets in whole blood. The present investigation indicates that platelets primed with minute amounts of arachidonic acid or collagen can be activated, in human whole blood, by oxygen-reactive species released by PMN

Hydrogen peroxide as trigger of platelet aggregation.

In order to verify if H2O2 affects platelet function, platelet-rich plasma and human washed platelets were incubated with subthreshold concentrations (STC) of collagen or arachidonic acid or ADP and/or with 75-150-mu-M H2O2. While H2O2 alone did not affect platelet aggregation, it amplified platelet aggregation response in samples stimulated with STC of arachidonic acid and collagen but not in samples stimulated with STC of ADP. When platelets were preventively treated with aspirin, a cyclooxygenase inhibitor, the platelet activation by H2O2 was not observed. Thromboxane A2 (TxA2) was not produced by human washed platelets stimulated with STC of arachidonic acid, collagen or by H2O2 alone. On the contrary, when STC of agonists were tested on platelets supplemented with H2O2 an evident TxA2 production was seen. This effect was prevented by aspirin pretreatment or by the addition of catalase, an enzyme which destroys H2O2. This study suggests that H2O2 triggers the activation of platelets exposed to STC of collagen and arachidonic acid, via the cyclooxygenase pathway

Replay to: Lipoprotein (a) and chronic obstructive pulmonary disease.

Lettera di risposta ad alcune osservazioni sull'articolo pubblicato su Atherosclerosis 1999, 147(2); 249-25

Association between high values of D-dimer and Tissue-plasminogen activator activity and first gastrointestinal bleeding in cirrhotic patients

Abstract Cirrhotic patients with decompensated state and high serum levels of fibrin(ogen) degradation products are at high risk of bleeding. The aim of this study was to further analyse the relationship between hyperfibrinolysis and bleeding in cirrhosis by measuring plasma values of D-dimer and tissue plasminogen activator (t-PA) activity. One-hundred-twelve cirrhotic patients with oesophageal varices and without previous upper-gastrointestinal bleeding entered the study and were followed-up for 3 years. Patients were considered to have hyperfibrinolysis if they concomitantly had high values of D-dimer and t-PA activity. During the follow-up 34 (30%) patients bled. They had more severe liver failure (p = 0.0001) and variceal size (p = 0.0031) and higher prevalence of ascites (p = 0.0003), varices with red signs and hyperfibrinolysis (p = 0.0001) than patients who did not bleed. Multivariate analysis disclosed hyperfibrinolysis as the only marker predictive of bleeding (Hazard Ratio = 42.5, p < 0.001). Our findings suggest that screening for hyperfibrinolysis may be useful to identify cirrhotic patients at risk of bleeding