Planning Matters: A Document Analysis of 24 Portuguese Health Programmes.

Background: Health planning is essential for effective public health interventions and optimal resource utilisation. The Portuguese Directorate-General of Health has a long history of developing health plans and programmes, for communicable and noncommunicable diseases, and their determinants. This study aimed to review the current 24 programmes and assess the adequacy of their structure and content.

Development and evaluation of nanostructured systems for cutaneous delivery of HS-releasing corticosteroids for skin inflammatory diseases.

Psoriasis is an immune-mediated chronic inflammatory disease that causes major psychosocial impact. Topical corticosteroids represent the standard pharmacological treatment for mild-to-moderate disease, but their local and systemic adverse effects reinforce the need for treatment innovations. Here we developed lamellar phase-based formulations for topical delivery of a hybrid dexamethasone and hydrogen sulfide (HS) donor molecule (Dexa-TBZ), aiming to potentiate the effects of the glucocorticoid with HS.

Targeting Myeloperoxidase Ameliorates Gouty Arthritis: A Virtual Screening Success Story.

This study presents a new approach for identifying myeloperoxidase (MPO) inhibitors with strong in vivo efficacy. By combining inhibitor-like rules and structure-based virtual screening, the pipeline achieved a 70% success rate in discovering diverse, nanomolar-potency reversible inhibitors and hypochlorous acid (HOCl) scavengers. Mechanistic analysis identified RL6 as a genuine MPO inhibitor and RL7 as a potent HOCl scavenger.

Disruption of Atrial Rhythmicity by the Air Pollutant 1,2-Naphthoquinone: Role of Beta-Adrenergic and Sensory Receptors.

The combustion of fossil fuels contributes to air pollution (AP), which was linked to about 8.79 million global deaths in 2018, mainly due to respiratory and cardiovascular-related effects. Among these, particulate air pollution (PM2.

TRPA1 channel mediates methylglyoxal-induced mouse bladder dysfunction.

The transient receptor potential ankyrin 1 channel (TRPA1) is expressed in urothelial cells and bladder nerve endings. Hyperglycemia in diabetic individuals induces accumulation of the highly reactive dicarbonyl compound methylglyoxal (MGO), which modulates TRPA1 activity. Long-term oral intake of MGO causes mouse bladder dysfunction.

Hydrogen Sulfide Signaling in the Tumor Microenvironment: Implications in Cancer Progression and Therapy.

Cancer is a complex and heterotypic structure with a spatial organization that contributes to challenges in therapeutics. Enzymes associated with producing the gasotransmitter hydrogen sulfide (HS) are differentially expressed in tumors. Indeed, critical and paradoxical roles have been attributed to HS in cancer-promoting characteristics by targeting both cancer cells and their milieu.

Beneficial Effects of Two Hydrogen Sulfide (HS)-Releasing Derivatives of Dexamethasone with Antioxidant Activity on Atopic Dermatitis in Mice.

Hydrogen sulfide (HS) is particularly produced in the skin, where it participates in the regulation of inflammation, pruritus, cytoprotection, scarring, and angiogenesis. In this study, we compared the effects of dexamethasone (Dex) with two HS-releasing Dex derivatives in a murine model of atopic dermatitis (AD) induced by topical application of 2,4-dinitrochlorobenzene (DNCB). After sensitization with DNCB, the animals were topically treated for five consecutive days with either the HS-releasing compounds 4-hydroxy-thiobenzamide (TBZ) and 5-(p-hydroxyphenyl)-1,2-dithione-3-thione (ADT-OH), Dex, or the derivatives Dex-TBZ or Dex-ADT.

salivary gland extract alleviates acute itching by blocking TRPA1 channels.

() saliva induces a variety of anti-inflammatory and immunomodulatory activities. Interestingly, although it is known that mosquito bites cause allergic reactions in sensitised hosts, the primary exposure of humans to does not evoke significant itching. Whether active components in the saliva of can counteract the normal itch reaction to injury produced by a histaminergic or non-histaminergic pathway in vertebrate hosts is unknown.

Subchronic exposure to 1,2-naphthoquinone induces adipose tissue inflammation and changes the energy homeostasis of mice, partially due to TNFR1 and TLR4.

Air pollution affects energy homeostasis detrimentally. Yet, knowledge of how each isolated pollutant can impact energy metabolism remains incomplete. The present study was designed to investigate the distinct effects of 1,2-naphthoquinone (1,2-NQ) on energy metabolism since this pollutant increases at the same rate as diesel combustion.

Role of Gasotransmitters in Inflammatory Edema.

Nitric oxide (NO), carbon monoxide (CO), and hydrogen sulfide (HS) are, to date, the identified members of the gasotransmitter family, which consists of gaseous signaling molecules that play central roles in the regulation of a wide variety of physiological and pathophysiological processes, including inflammatory edema. Recent studies show the potential anti-inflammatory and antiedematogenic effects of NO-, CO-, and HS-donors . In general, it has been observed that the therapeutical effects of NO-donors are more relevant when administered at low doses at the onset of the inflammatory process.

Enhanced efficacy of formoterol-montelukast salt in relieving asthma features and in preserving β2-agonists rescue therapy.

Adrenergic β2-agonists represent a mainstay in asthma management. Their chronic use has been associated with decreased bronchoprotection and rebound hyperresponsiveness. Here we investigate on the possible therapeutic advantage of a pharmacological association of β2-agonists with montelukast, a highly selective leukotriene receptor antagonist, in modulating bronchial reactivity and controlling asthma features.

Myrtenol Reduces Orofacial Nociception and Inflammation in Mice Through p38-MAPK and Cytokine Inhibition.

Orofacial pain is one of the commonest and most complex complaints in dentistry, greatly impairing life quality. Preclinical studies using monoterpenes have shown pharmacological potential to treat painful conditions, but the reports of the effects of myrtenol on orofacial pain and inflammation are scarce. The aim of this study was to evaluate the effect of myrtenol in experimental models of orofacial pain and inflammation.

The Symbiotic Effect of a New Nutraceutical with Yeast β-Glucan, Prebiotics, Minerals, and (Silymarin) for Recovering Metabolic Homeostasis via , , and Gene Expression in a Type-2 Diabetes Obesity Model.

The use of natural products and derivatives for the prevention and control of non-communicable chronic diseases, such as type-2 diabetes (T2D), obesity, and hepatic steatosis is a way to achieve homeostasis through different metabolic pathways. Thus, male C57BL/6 mice were divided into the following groups: high-fat diet (HFD) vehicle, HFD + Supplemented, HFD + Supplemented_S, and isolated compounds. The vehicle and experimental formulations were administered orally by gavage once a day over the four weeks of the diet (28 consecutive days).

Vasorelaxant Activity of AP39, a Mitochondria-Targeted HS Donor, on Mouse Mesenteric Artery Rings In Vitro.

Mitochondria-targeted hydrogen sulfide (HS) donor compounds, such as compound AP39, supply HS into the mitochondrial environment and have shown several beneficial in vitro and in vivo effects in cardiovascular conditions such as diabetes and hypertension. However, the study of their direct vascular effects has not been addressed to date. Thus, the objective of the present study was to analyze the effects and describe the mechanisms of action of AP39 on the in vitro vascular reactivity of mouse mesenteric artery.

Microemulsion for Prolonged Release of Fenretinide in the Mammary Tissue and Prevention of Breast Cancer Development.

The need of pharmacological strategies to preclude breast cancer development motivated us to develop a non-aqueous microemulsion (ME) capable of forming a depot after administration in the mammary tissue and uptake of interstitial fluids for prolonged release of the retinoid fenretinide. The selected ME was composed of phosphatidylcholine/tricaprylin/propylene glycol (45:5:50, w/w/w) and presented a droplet diameter of 175.3 ± 8.

Lipopolysaccharide reduces urethral smooth muscle contractility via cyclooxygenase activation.

Lipopolysaccharide (LPS) is a component of gram-negative bacteria wall that elicits inflammatory response in the host through the toll-like receptor 4 (TLR4) activation. In the lower urinary tract (LUT), bacteria-derived LPS has been associated with lower urinary tract symptoms (LUTS); however, little is known about the effects of LPS in the urethral smooth muscle (USM). In the present study, we evaluated the functional and molecular effects of LPS in mouse USM in vitro, focusing on the LPS-induced TLR4-signaling pathway.

Factors associated with preschool children's sleep bruxism.

Objective: To evaluate the prevalence of sleep bruxism, related factors, and quality of life of preschool children and their families.

Method: The sample was 475 children between 4 and 5 years old enrolled in schools in the city of Bauru-Brazil. Parents/legal guardians answered two questionnaires, one to assess the presence of bruxism and related factors and another that was the validated Brazilian version of the Early Childhood Oral Health Impact Scale (B-ECOHIS).

The potential anti-inflammatory and anti-nociceptive effects of rat hemopressin (PVNFKFLSH) in experimental arthritis.

Inflammatory arthritis, such as rheumatoid arthritis (RA), stands out as one of the main sources of pain and impairment to the quality of life. The use of hemopressin (PVNFKFLSH; Hp), an inverse agonist of type 1 cannabinoid receptor, has proven to be effective in producing analgesia in pain models, but its effect on neuro-inflammatory aspects of RA is limited. In this study, antigen-induced arthritis (AIA) was evoked by the intraarticular (i.

Molecular mechanism and health effects of 1,2-Naphtoquinone.

Extensive literature regarding the health side effects of ambient pollutants (AP) are available, such as diesel exhaust particles (DEPs), but limited studies are available on their electrophilic contaminant 1,2-Naphthoquinone (1,2-NQ), enzymatically derived from naphthalene. This review summarizes relevant toxicologic and biological properties of 1,2-NQ as an environmental pollutant or to a lesser degree as a backbone in drug development to treat infectious diseases. It presents evidence of 1,2-NQ-mediated genotoxicity, neurogenic inflammation, and cytotoxicity due to several mechanistic properties, including the production of reactive oxygen species (ROS), that promote cell damage, carcinogenesis, and cell death.

Enhanced Analgesic Effects and Gastrointestinal Safety of a Novel, Hydrogen Sulfide-Releasing Anti-Inflammatory Drug (ATB-352): A Role for Endogenous Cannabinoids.

The covalent linking of nonsteroidal anti-inflammatory drugs to a hydrogen sulfide (HS)-releasing moiety has been shown to dramatically reduce gastrointestinal (GI) damage and bleeding, as well as increase anti-inflammatory and analgesic potency. We have tested the hypothesis that an HS-releasing derivative of ketoprofen (ATB-352) would exhibit enhanced efficacy without significant GI damage in a mouse model of allodynia/hyperalgesia. ATB-352 was significantly more potent and effective as an analgesic than ketoprofen and did not elicit GI damage.

Hydrogen sulfide inhibits apoptosis and protects the bronchial epithelium in an allergic inflammation mice model.

Studies suggest that hydrogen sulfide (HS) plays a relevant and beneficial role in the pathophysiology of pulmonary allergic diseases, such as asthma. These diseases may be triggered by changes in airway epithelium caused by repeated exposure to environmental allergens. This study aimed to investigate whether HS protects against bronchial epithelium apoptosis in allergic inflammation in mice.

Hydrogen sulfide and dermatological diseases.

Skin diseases constitute a major health problem affecting a high proportion of the population every day and have different aetiologies that include inflammation, infections, and tumours. Hydrogen sulfide (H S) is a gaseous signalling molecule recognized as a gasotransmitter together with NO and carbon monoxide. Under physiological conditions, H S is produced in the skin by enzymic pathways and plays a physiological role in a variety of functions, such as vasodilatation, cell proliferation, apoptosis, and inflammation.

Exercise training restores the myogenic response in skeletal muscle resistance arteries and corrects peripheral edema in rats with heart failure.

Impairment of the myogenic response can affect capillary hydrostatic pressure and contribute to peripheral edema and exercise intolerance, which are markers of heart failure (HF). The aim of this study was to assess the effects of exercise training (ET) on myogenic response in skeletal muscle resistance arteries and peripheral edema in HF rats, focusing on the potential signaling pathways involved in these adjustments. Male Wistar rats were submitted to either coronary artery occlusion or a sham-operated surgery.

The inclusion complex of carvacrol and β-cyclodextrin reduces acute skeletal muscle inflammation and nociception in rats.

Background: Skeletal muscle inflammation is strongly associated with pain and may impair regeneration and functional recovery after injury. Since anti-inflammatory and antinociceptive effects have been described for the inclusion complex of carvacrol and β-cyclodextrin (βCD-carvacrol), this study investigated the effects of βCD-carvacrol in a model of acute skeletal muscle inflammation.

Methods: Muscle injury was induced in male Wistar rats by injection of 3% carrageenan in the gastrocnemius muscle.