An Unusual Hunting Accident: A Case Report.

In Hungary, possessing certain weapons (e.g. firearms, bows, air pistols, and air guns mainly over 7.

Omecamtiv Mecarbil in the treatment of heart failure: the past, the present, and the future.

Heart failure, a prevailing global health issue, imposes a substantial burden on both healthcare systems and patients worldwide. With an escalating prevalence of heart failure, prolonged survival rates, and an aging demographic, an increasing number of individuals are progressing to more advanced phases of this incapacitating ailment. Against this backdrop, the quest for pharmacological agents capable of addressing the diverse subtypes of heart failure becomes a paramount pursuit.

Lethal threat in the use of glass doors at home: A case report.

Background: Various instruments, including glass fragments, can inflict sharp-force damage, resulting in injuries ranging from superficial wounds to life-threatening trauma. This case report explores the lethal consequences of a 78-year-old man accidentally sustaining a stabbed-incised wound after falling against an ordinary glass door, leading to fatal bleeding from the subclavian artery.

Case Report: The man's fall caused a sharp-edged glass fragment to penetrate his neck, resulting in a fatal outcome despite resuscitation attempts.

The Novel Cardiac Myosin Activator Danicamtiv Improves Cardiac Systolic Function at the Expense of Diastolic Dysfunction In Vitro and In Vivo: Implications for Clinical Applications.

Recent cardiotropic drug developments have focused on cardiac myofilaments. Danicamtiv, the second direct myosin activator, has achieved encouraging results in preclinical and clinical studies, thus implicating its potential applicability in the treatment of heart failure with reduced ejection fraction (HFrEF). Here, we analyzed the inotropic effects of danicamtiv in detail.

A Central Role for TRPM4 in Ca-Signal Amplification and Vasoconstriction.

Transient receptor potential melastatin-4 (TRPM4) is activated by an increase in intracellular Ca concentration and is expressed on smooth muscle cells (SMCs). It is implicated in the myogenic constriction of cerebral arteries. We hypothesized that TRPM4 has a general role in intracellular Ca signal amplification in a wide range of blood vessels.

TRPV1 in arteries enables a rapid myogenic tone.

Arterioles maintain blow flow by adjusting their diameter in response to changes in local blood pressure. In this process called the myogenic response, a vascular smooth muscle mechanosensor controls tone predominantly through altering the membrane potential. In general, myogenic responses occur slowly (minutes).

Omecamtiv mecarbil evokes diastolic dysfunction and leads to periodic electromechanical alternans.

Omecamtiv mecarbil (OM) is a promising novel drug for improving cardiac contractility. We tested the therapeutic range of OM and identified previously unrecognized side effects. The Ca sensitivity of isometric force production (pCa) and force at low Ca levels increased with OM concentration in human permeabilized cardiomyocytes.

TRPV1 expressed throughout the arterial circulation regulates vasoconstriction and blood pressure.

Key Points: The functional roles of the capsaicin receptor, TRPV1, outside of sensory nerves are unclear. We mapped TRPV1 in the mouse circulation, revealing extensive expression in the smooth muscle of resistance arterioles supplying skeletal muscle, heart and adipose tissue.  Activation of TRPV1 in vascular myocytes constricted arteries, reduced coronary flow in isolated hearts and increased systemic blood pressure.

Carbonic Anhydrase Inhibitor Acetazolamide Enhances CHOP Treatment Response and Stimulates Effector T-Cell Infiltration in A20/BalbC Murine B-Cell Lymphoma.

The inhibition of cancer-related carbonic anhydrase (CA) activity is a promising way to intensify anti-tumor responses. In vitro data suggest improved efficacy of cytotoxic drugs in combination with CA-inhibitors in several cancer types. Despite accumulating data on CA-expression, experimental or clinical studies towards B-cell lymphoma therapy are missing.

Transglutaminase 2 Has Metabolic and Vascular Regulatory Functions Revealed by In Vivo Activation of Alpha1-Adrenergic Receptor.

The multifunctional tissue transglutaminase has been demonstrated to act as α1-adrenergic receptor-coupled G protein with GTPase activity in several cell types. To explore further the pathophysiological significance of this function we investigated the in vivo effects of the α1-adrenergic receptor agonist phenylephrine comparing responses in wild type and TG2 mice. Injection of phenylephrine, but not a beta3-adrenergic agonist (CL-316,243), resulted in the long-term decline of the respiratory exchange ratio and lower lactate concentration in TG2 mice indicating they preferred to utilize fatty acids instead of glucose as fuels.

Analysis of the effect of locally applied inhomogeneous static magnetic field-exposure on mouse ear edema--a double blind study.

The effect static magnetic field (SMF)-exposure may exert on edema development has been investigated. A 6 h long whole-body (WBSMF) or local (LSMF), continuous, inhomogeneous SMF-exposure was applied on anesthetized mice in an in vivo model of mustard oil (MO)-induced ear edema. LSMF was applied below the treated ear, below the lumbar spine, or below the mandible.

Analgesic and anti-inflammatory effectiveness of sitagliptin and vildagliptin in mice.

To validate the potential anti-inflammatory and analgesic role of sita- and vildagliptin, five different experimental models were used in mice: i) mustard oil-induced ear edema, ii) neutrophil accumulation, iii) mechanical and iv) thermal touch sensitivity in complete Freund's adjuvant-induced arthritis and v) capsaicin-induced plasma extravasation in the urinary bladder. For the complete examination period in i) the dose of 10mg sitagliptin as well as 1-10mg vildagliptin was found to significantly decrease ear edema as compared to positive control (p<0.05, n=8/group).

The effect of whole-body, repetitive, inhomogeneous static magnetic field-exposure on the symptoms of experimental autoimmune encephalomyelitis in mice.

Experimental autoimmune encephalomyelitis (EAE) is a model for human multiple sclerosis (MS) in rodents. Static magnetic field (SMF)-exposure was shown to be beneficial in specific cases of inflammatory background, where it suppresses symptoms. The null-hypothesis was that animals with induced EAE exposed to SMF would show different seriousness of symptoms, than those in the sham-exposed control group.

Different desensitization patterns for sensory and vascular TRPV1 populations in the rat: expression, localization and functional consequences.

Background And Purpose: TRPV1 is expressed in sensory neurons and vascular smooth muscle cells, contributing to both pain perception and tissue blood distribution. Local desensitization of TRPV1 in sensory neurons by prolonged, high dose stimulation is re-engaged in clinical practice to achieve analgesia, but the effects of such treatments on the vascular TRPV1 are not known.

Experimental Approach: Newborn rats were injected with capsaicin for five days.

Vanilloid receptor-1 (TRPV1) expression and function in the vasculature of the rat.

Transient receptor potential (TRP) cation channels are emerging in vascular biology. In particular, the expression of the capsaicin receptor (TRPV1) was reported in vascular smooth muscle cells. This study characterized the arteriolar TRPV1 function and expression in the rat.

The surmountable effect of FSCPX, an irreversible A(1) adenosine receptor antagonist, on the negative inotropic action of A(1) adenosine receptor full agonists in isolated guinea pig left atria.

A1 adenosine receptors (A1 receptors) are widely expressed in mammalian tissues; therefore attaining proper tissue selectivity is a cornerstone of drug development. The fact that partial agonists chiefly act on tissues with great receptor reserve can be exploited to achieve an appropriate degree of tissue selectivity. To the best of our knowledge, the A1 receptor reserve has not been yet quantified for the atrial contractility.

Structure-activity relationships of vanilloid receptor agonists for arteriolar TRPV1.

Background And Purpose: The transient receptor potential vanilloid 1 (TRPV1) plays a role in the activation of sensory neurons by various painful stimuli and is a therapeutic target. However, functional TRPV1 that affect microvascular diameter are also expressed in peripheral arteries and we attempted to characterize this receptor.

Experimental Approach: Sensory TRPV1 activation was measured in rats by use of an eye wiping assay.

Exposure to static magnetic field delays induced preterm birth occurrence in mice.

Objective: The purpose of this study was to demonstrate that daily 40-minute whole body exposure to an inhomogeneous static magnetic field (SMF) prolongs induced preterm birth (PTB) in mice.

Study Design: The murine model for PTB induction was performed by the administration of 25 μg/animal lipopolysaccharide (LPS) intraperitoneally. The applied SMF was an inhomogeneous gradient field with 2.

Daily exposure to inhomogeneous static magnetic field significantly reduces blood glucose level in diabetic mice.

Purpose: The present study was designed to reveal, whether the 30 min daily full body exposure of mice to an inhomogeneous static magnetic field (SMF) has a statistically significant effect on diabetic neuropathy.

Materials And Methods: Three different doses (100, 150, or 200 mg/kg) of streptozotocin (STZ) were administered intraperitoneally in groups of mice to induce diabetes. Body weight, blood glucose level and the nociceptive temperature threshold of mice were monitored for a period of 12 weeks.

Tissue-specific regulation of microvascular diameter: opposite functional roles of neuronal and smooth muscle located vanilloid receptor-1.

The transient receptor potential type V1 channel (vanilloid receptor 1, TRPV1) is a Ca(2+)-permeable nonspecific cation channel activated by various painful stimuli including ischemia. We hypothesized that TRPV1 is expressed in the arterioles and is involved in the regulation of microvascular tone. We found that TRPV1 stimulation by capsaicin (intra-arterial administration) of the isolated, perfused right hind limb of the rat increased vascular resistance (by 98 +/- 21 mm Hg at 10 mug) in association with decreased skeletal muscle perfusion and elevation of skin perfusion (detected by dual-channel laser Doppler flowmetry).

Neurogenic insulin resistance in guinea-pigs with cisplatin-induced neuropathy.

The aim of the present work was to study whether neurotoxicity produced by cisplatin modified tissue insulin sensitivity in guinea-pigs. One week after selective sensory denervation of the anterior hepatic plexus by means of perineurial 2% capsaicin treatment, hyperinsulinaemic euglycaemic glucose clamp were performed to estimate insulin sensitivity in male guinea-pigs. The guinea-pigs underwent regional sensory denervation of the anterior hepatic plexus exhibited insulin resistance, whereas systemic capsaicin desensitization increased insulin sensitivity.

Sensory nitrergic meningeal vasodilatation and non-nitrergic plasma extravasation in anaesthesized rats.

The aim of the present study was to evaluate the role of nitric oxide (NO) of sensory neural origin in neurogenic inflammatory response in the trigeminovascular system. Antidromic vasodilatation and plasma extravasation in response to electrical stimulation (15 V, 5 Hz, 0.5 ms, 100 impulses) of the trigeminal ganglion were investigated in the dura mater and nasal mucosa/upper eyelid by laser Doppler flowmetry and [(125)I]-labelled bovine serum albumin, respectively.

Cyclic GMP-mediated activation of a glibenclamide-sensitive mechanism in the rabbit sphincter of Oddi.

We investigated whether glibenclamide-sensitive potassium channels are involved in cyclic GMP (cGMP)-mediated relaxation of the rabbit Oddi's sphincter. Changes in isometric tension were measured in the presence of atropine (1 microM) and guanethidine (4 microM). Concentration-response curves for nitroglycerin, vasoactive intestinal polypeptide (VIP), and sodium nitroprusside (SNP) were shifted to the right in the presence of (p-chloro-D-Phe6, Leu17)-VIP (VIPa), a VIP receptor antagonist.

Development of insulin resistance by nitrate tolerance in conscious rabbits.

Clinical evidence has been raised to suggest that transdermal nitroglycerin increases the sensitivity of peripheral tissues to the hypoglycemic effect of insulin. In this study we determined whether development of tolerance to the hypotensive effect of nitroglycerin also resulted in tolerance to the insulin-sensitizing effect in rabbits. Intravenous glucose disposal and hyperinsulinemic euglycemic glucose clamp studies were performed on naive and hemodynamic nitrate tolerant conscious New Zealand white rabbits.