Bactericidal activities of woven cotton and nonwoven polypropylene fabrics coated with hydroxyapatite-binding silver/titanium dioxide ceramic nanocomposite “Earth-plus”

Background: Bacteria from the hospital environment, including linens and curtains, are often responsible for hospital-associated infections. The aim of the present study was to evaluate the bactericidal effects of fabrics coated with the hydroxyapatite-binding silver/titanium dioxide ceramic nanocomposite "Earth-plus". Methods: Bactericidal activities of woven and nonwoven fabrics coated with Earth-plus were investigated by the time-kill curve method using nine bacterial strains, including three Staphylococcus aureus, three Escherichia coli, and three Pseudomonas aeruginosa strains. Results: The numbers of viable S. aureus and E. coli cells on both fabrics coated with Earth-plus decreased to below 2 log(10) colony-forming units/mL in six hours and reached the detection limit in 18 hours. Viable cell counts of P. aeruginosa on both fabrics coated with Earth-plus could not be detected after 3-6 hours. Viable cells on woven fabrics showed a more rapid decline than those on nonwoven fabrics. Bacterial cell counts of the nine strains on fabrics without Earth-plus failed to decrease even after 18 hours. Conclusion: Woven cotton and nonwoven polypropylene fabrics were shown to have excellent antibacterial potential. The woven fabric was more bactericidal than the nonwoven fabric

Dermorphin tetrapeptide誘導体Tyr-D-Arg-Phe-β-AlaおよびTyr-D-Arg-Phe-β-Ala-NH_2の鎮痛作用発現におけるμ1受容体の関与

Involvement of μ1-opioid receptor on the antinociception induced by dermorphin tetrapeptide analogues Try-D-Arg-Phe-β-Ala (TAPA) and Tyr-D-Arg-Phe-β-Ala-NH_2 (TAPA-NH_2) were determined in mice, using a tail-pressure test and formalin test. TAPA and TAPA-NH_2 injected i. c. v. and i. t. produced dose-dependent antinociception in both assays. In the tail-pressure test, the antinociception induced by i. c. v. and i. t. injected TAPA, but not TAPA-NH_2, was significantly attenuated by the pretreatment with naloxonazine, selective antagonist for μ1-opioid receptor. Moreover, naloxonazine also significantly attenuated the antinociception induced by i. c. v. injected TAPA, but not TAPA-NH_2 in formalin test. In contrast, the antinociception induced by both TAPA and TAPA-NH_2 given i. t. was significantly attenuated by the pretreatment with naloxonazine in formalin test. The present results suggest that TAPA and TAPA-NH_2 should be considered to be selective agonist for μ1-and μ2-opioid receptors, respectively. The C-terminal amidation may be the critical portion for TAPA-NH_2 to distinguish μ1-and μ2-opioid receptors

Endomorphin analogues containing D-Pro(2) discriminate different μ-opioid receptor mediated antinociception in mice

The antagonistic actions of D-Pro(2)-endomorphins on inhibition of the paw withdrawal response by endomorphins were studied in mice. D-Pro(2)-endomorphin-1 and D-Pro(2)-endomorphin-2, injected intrathecally (i.t.), had no significant effect on the nociceptive thermal threshold alone. When D-Pro(2)-endomorphin-1 (0.05–0.1 pmol) was injected simultaneously with i.t. endomorphin-1 (5.0 nmol) or endomorphin-2 (5.0 nmol), antinociception induced by endomoprhin-1 was reduced significantly, whereas endomorphin-2-induced antinociception was not affected by D-Pro(2)-endomorphin-1. Antinociception induced by i.t. endomorphin-2 (5.0 nmol) was reduced significantly by its analogue, D-Pro(2)-endomorphin-2 (100 pmol), but not by D-Pro(2)-endomorphin-1. D-Pro(2)-endomorphin-1. D-Pro(2)-endomorphin-1 also antagonized the antinociceptive effect of i.t. DAMGO, a μ-opioid receptor agonist, whereas D-Pro(2)-endomorphin-2 failed to reduce the effect of DAMGO. These results suggest that endomorphin analogues containing D-Pro(2) are able to discriminate the antinociceptive actions of μ(1)- and μ(2)-opioid receptor agonists at the spinal cord level

Pharmacotechnological Advances for Clinical Translation of Essential Oils for the Treatment of Pain and Agitation in Severe Dementia

The demand for natural products is steadily increasing, and pharmacotechnological engineering is needed to allow rigorous investigation of their efficacy and safety in clinical conditions representing still unmet needs. Among aged patients affected by dementia, up to 80% of residents in nursing homes suffer from chronic pain and 97% from fluctuant neuropsychiatric symptoms (NPS), of which the most challenging is agitation. It is, at least in part, due to undertreated pain and treated with antipsychotics almost doubling the risk of death. In the frame of a scoping review assessing the existence of essential oils undergoing engineering pharmacotechnological processes using solid lipid nanoparticle delivery systems for clinical translation in pain and/or neuropsychiatric symptoms of dementia following the Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR), here we identified that the sole essential oil engineered to overcome the criticisms of aromatherapy clinical trials in pain and dementia is the essential oil of bergamot (BEO). Therefore, we present the process leading to the actually ongoing randomized, double-blind, placebo-controlled NCT04321889 clinical trial to assess the efficacy and safety of intervention with bergamot in the management of agitation and pain in severe dementia to be followed also for the proof of concept of efficacy and safety of other essential oils

Nociceptin (1–7) antagonizes nociceptin-induced hyperalgesia in mice

Nociceptin and its N-terminal fragment, nociceptin (1–7), were administered intrathecally (i.t.) into conscious mice. Nociceptin (3.0 fmol) produced a significant reduction in the nociceptive thermal threshold (hyperalgesia) measured as the tail-flick and paw-withdrawal responses. Nociceptin (1–7), injected i.t., at 150–1200 fmol had no significant effect. However, when nociceptin (1–7) (150–1200 fmol) was injected simultaneously with nociceptin (3.0 fmol), nociceptin-induced hyperalgesia was significantly reduced. Analgesia induced by a high dose (1200 pmol) of nociceptin was not antagonized by co-administration of nociceptin (1–7) (1200 fmol). These results suggest that N-terminal fragments of nociceptin formed endogenously could modulate the hyperalgesic action of nociceptin in the spinal cord

Antispasmodic Effect of Bergamot Essential Oil on Rat Isolated Gut Tissues

Preclinical data indicate that bergamot essential oil (BEO) can modulate the synaptic functions within the central nervous system (CNS). Particularly, several data shows that essential oil is endowed with reproducible analgesic and anxiolytic effects that may derived from the ability to modulate the excitatory and inhibitory neurotransmission in the CNS. Although there are differences in the functional complexity of the enteric nervous system (ENS), it is likely that the phytocomplex has biological properties in gut superimposable to those showed in the CNS. Accordingly, the aim of this study was to investigate ex-vivo the effect of bergamot essential oil and its main constituents on the contractile activity of rat isolated colon, jejunum and ileum induced by different muscle stimulants such as acetylcholine (10−6 M) and potassium chloride (80 mM). Our present data demonstrate that BEO inhibits cholinergically- and non cholinergically-mediated contractions in rat isolated gut and that linalool is the most active component. These results suggest that the phytocomplex might be useful in the treatment of spastic disorders in ENS mainly characterized by the presence of pain; incidentally, irritable bowel syndrome (IBS) is a painful condition in which a role for neurotransmitter dysfunction has been envisaged. More investigation is required for clinical translation of the present data

Neuropharmacology of the Neuropsychiatric Symptoms of Dementia and Role of Pain: Essential Oil of Bergamot as a Novel Therapeutic Approach

Aging of the population makes of dementia a challenge for health systems worldwide. The cognitive disturbance is a serious but not the only issue in dementia; behavioral and psychological syndromes known as neuropsychiatric symptoms of dementia remarkably reduce the quality of life. The cluster of symptoms includes anxiety, depression, wandering, delusions, hallucinations, misidentifications, agitation and aggression. The pathophysiology of these symptoms implicates all the neurotransmitter systems, with a pivotal role for the glutamatergic neurotransmission. Imbalanced glutamatergic and GABAergic neurotransmissions, over-activation of the extrasynaptic N-methyl-D-aspartate (NMDA) receptors and alterations of the latter have been linked to the development of neuropsychiatric symptoms experienced by almost the entire demented population. Drugs with efficacy and safety for prevention or long term treatment of these disorders are not available yet. Aromatherapy provides the best evidence for positive outcomes in the control of agitation, the most resistant symptom. Demented patients often cannot verbalize pain, resulting in unrelieved symptoms and contributing to agitation. Bergamot essential oil provides extensive preclinical evidence of analgesic properties. Incidentally, the essential oil of bergamot induces anxyolitic-like effects devoid of sedation, typical of benzodiazepines, with a noteworthy advantage for demented patients. These data, together with the reported safety profile, form the rational basis for bergamot as a neurotherapeutic to be trialed for the control of behavioral and psychological symptoms of dementia

Nociceptin-induced scratching, biting and licking in mice: involvement of spinal NK(1) receptors

1. Intrathecal (i.t.) injection of nociceptin at small doses (fmol order) elicited a behavioural response consisting of scratching, biting and licking in conscious mice. Here we have examined the involvement of substance P-containing neurons by using i.t. injection of tachykinin neurokinin (NK)(1) receptor antagonists and substance P (SP) antiserum. 2. Nociceptin-induced behavioural response was evoked significantly 5–10 min after i.t. injection and reached a maximum at 10–15 min. Dose-dependency of the induced response showed a bell-shaped pattern from 0.375–30.0 fmol, and the maximum effect was observed at 3.0 fmol. 3. The behavioural response elicited by nociceptin (3.0 fmol) was dose-dependently inhibited by intraperitoneal (i.p.) administration of morphine. 4. The NK(1) receptor antagonists, CP-96,345, CP-99,994 and sendide, inhibited nociceptin-induced behavioural response in a dose-dependent manner. A significant antagonistic effect of [D-Phe(7), D-His(9)]SP (6–11), a selective antagonist for SP receptors, was observed against nociceptin-induced response. The NK(2) receptor antagonist, MEN-10376, had no effect on the response elicited by nociceptin. 5. Pretreatment with SP antiserum resulted in a significant reduction of the response to nociceptin. No significant reduction of nociceptin-induced response was detected in mice pretreated with NKA antiserum. 6. The N-methyl-D-aspartate (NMDA) receptor antagonists, dizocilpine (MK-801) and D(−)-2-amino-5-phosphonovaleric acid (APV) (D-APV), and L-N(G)-nitro arginine methyl ester (L-NAME), a nitric oxide (NO) synthase inhibitor, failed to inhibit nociceptin-induced behavioural response. 7. The present results suggest that SP-containing neurons in the mouse spinal cord may be involved in elicitation of scratching, biting and licking behaviour following i.t. injection of nociceptin