Neurobiology of Pain in Children: An Overview

The evaluation of pain in the newborn and the infant is difficult because pain is mainly a subjective phenomenon. Until a few years ago, several myths persisted. First, the myth that children, especially infants, do not feel pain the way adults do, therefore there is no untoward consequences for them. Second, lack of assessment and reassessment for the presence of pain. Third, misunderstanding of how to conceptualise and quantify a subjective experience. Fourth, lack of knowledge of pain treatment. Fifth, the notion that addressing pain in children takes too much time and effort, in ultimate analysis resulting in wasting time. Sixth, fears of hidden -and not easy to diagnose or prevent- adverse effects of analgesic medications, including respiratory depression and addiction. Finally, from a conceptual point of view, high thresholds of pain in neonates and infants were considered to be present by natural character, and useful in protecting infant from pain during birth and transit through the narrow vaginal channel

Circadian and ultradian rhythms in locomotory activity of inbred strains of mice

In this study we recorded locomotor activity of two inbred of mice (B6 and C) in two photoperiod conditions (LD 12:12 and DD) to characterize behavioural parameters of the endogenous rhythms of locomotor activity with particular attention to the ultradian rhythms. Literature reveals discordant data for these parameters, both for animals belonging to the same strain and to those in the same laboratory or monitored in the same conditions. Our results show that C strain has a shorter and unstable endogenous circadian period, while B6 strain has a longer and stable endogenous rhythm. In our study, B6 showed a longer and stable period than C, so we can confirm the presence of a genetic component underlying this trait. Ultradian rhythms are expressed independently of either the photoperiod or the circadian rhythm. There are no strain-dependent differences in the periods of 12, 8 and 4 h. The situation was different for the length of the ultradian period in the range 1-8 h and for the weighted power in the ranges 480-300 and 300-100 min, for which there were differences between photoperiods and strains

Migraine: An Overview

The pathophysiology of migraine is not completely understood and continues to be investigated. The complexity of interactions taking place in the sensory neuronal network with the mediation of all different neurotransmitters involved gives the measure of the extreme difficulty connected with the knowledge of migraine pathogenesis and in particular of its cardinal sign. Neuronal components are relevant in migraine pathophysiology: there could be a generalized interictal abnormal excitability of the cerebral cortex in migraine, possibly favoring the occurrence of spreading depression with consequent activation of the trigeminal system. Many theories have been formulated in these last sixty years about the pathogenesis of migraine and other forms of primary headache, but the problem is still far to be fully clarified. The present review is focused on the description of different theories on the migraine pathogenesis

Pharmaceutical Lipid Formulations of Amphotericin B for the Treatment of Human Leishmaniasis

The first description of a skin lesion, “Delhi button” dates back to Cunningham (1885) who reported the presence, on tissue sections, of bodies of 12.6 μm x 8.8 μm, presumably parasitic macrophages, containing "nucleoid bodies" which he believed to be spores belonging to Mycetozoa. But the first to describe the Leishmania parasite was, in 1898, a young man Russian military surgeon, named Borowsky. He investigated the cause of the "Sart button" at the military hospital in Tashkent. This paper, through the analysis of the studies carried out over the years proposes a description of the different therapeutic strategies for the treatment of leishmaniasis (advantages and criticalities of the same) and in particular an analysis detailed description of Amphotericin B, its mechanisms of action and pharmaceutical formulations, especially liposomal ones

Phytotherapeutic Strategy as a Powerful Approach for the Prevention and Therapy of Alzheimer's Disease

According to the World Health Organization and Alzheimer's Disease International there were about 35.6 million people suffering from dementia in 2010 with an estimated double increase in 2030, triple in 2050, with 7.7 million new cases. per year (1 every 4 seconds) and with an average survival, after diagnosis, of 4-8 years. Alzheimer's disease is generally associated with the elderly and with aging, which is why the symptoms of this disease are often ignored. In reality, Alzheimer's seems to affect people between the ages of 65 and 70, while more precocious and severe cases occur before the age of 65 and aging and stress can only worsen the symptoms. The sex most affected is female. It has been noted that dementia in industrialized countries affects about 8% of people over 65 and rises to over 20% after the age of eighty. This suggests that, very often, different factors such as lifestyle, stress and nutrition influence the speed and onset of this disease. To date, it is now known that the affected organ is the brain, such a complex and fascinating organ, but above all difficult to study and treat due to its complicated structure and organization. In fact, the treatment is based on pharmacological therapies, but although numerous research studies are underway to identify effective therapies in the treatment of dementia, the available interventions have not given definitive solutions to treat 6 this pathology. The therapeutic strategies available for dementias in addition to those of a pharmacological type are: psychosocial and integrated management for continuity of care and also psychotherapeutic support for families. In recent decades, however, we have focused on another aspect of this disease: how to prevent it? And this is where the use of medicinal plants comes into play to prevent and mitigate the onset of this disease. This type of approach is based on the use of medicinal plants; in particular the phytocomplex, contained in them, owes its activity to the synergy between its components. Plants produce secondary metabolites, organic compounds, which unlike the primary ones such as carbohydrates, proteins and fats, do not participate in the normal development and growth of the plant, but are developed by the plant to mediate the relationship with the external environment, carrying out important activities such as facilitate reproduction and therefore attract pollinating insects or act as a deterrent to the external environment. These compounds have very complex chemical structures that can be used as guiding compounds for the discovery of new drugs or for the development of nutraceutical or cosmeceutical remedies. In phytotherapy, medicinal plants that can be used for preventive purposes or as adjuvants in the treatment of Alzheimer's, are identified essentially starting from their antioxidant, anticholinesterase and anti-inflammatory properties, or as very often happens from all three. This paper reviews the plant species used in the prevention of Alzheimer's disease and as adjuvants in the treatment of Alzheimer's

Chemical and Functional Characterization of Propolis Collected from Different Areas of South Italy

This study investigated the chemical and functional characterization of propolis collected in southern Italy, in particular in Basilicata, a region rich in ecological and vegetative biodiversity. Sixteen samples of propolis, collected within a radius of 40 km from each other in the Basilicata region, showed significant differences between the chemical and functional parameters investigated: color index (L*, a*, b*; p < 0.05) and variation in chemical composition and antioxidant activities by ABTS and FRAP assays. In general, Lucanian propolis had a low content of waxes (p < 0.05) and a high content of resin (p < 0.05) and balsams (p < 0.05). The content of the total phenolic compounds and flavonoids was highly variable, as was the biological capacity. In conclusion, Lucanian propolis showed remarkable variability, highlighting significant diversification according to the geographical position and the diversity of the flora surrounding the apiary that the bees use as a source of resin. This study, therefore, contributes to the enhancement of the quality of propolis, laying the foundations for the production and marketing of propolis not only in the food industry but also in the pharmaceutical and cosmetic industries

Metabolic Syndrome and Inflammatory Cytokines in Psoriasis.

Obesity negatively affects the pathological states of chronic inflammation, such as Psoriasis and Psoriatic Arthritis. The inflammatory cytokines released by the adipose tissue determine, in addition to inflammation, a condition of insulin resistance, which is also a comorbidity of psoriasis. The state of chronic inflammation unites both psoriasis and obesity. The first is an autoimmune skin disease, where very thick skin layers are evident due to an abnormal proliferation of keratinocytes; obesity, on the other hand, represents one of the possible comorbidities of psoriasis the simultaneous presence in the same subject of two or more diseases

Clinical Phenotype of Pediatric and Adult Patients With Spinal Muscular Atrophy With Four SMN2 Copies: Are They Really All Stable?

Clinical phenotype; Pediatric patients; Spinal muscular atrophyFenotipo clínico; Pacientes pediátricos; Atrofia muscular espinalFenotip clínic; Pacients pediàtrics; Atròfia muscular espinalObjective The aim of this study was to provide an overview of the clinical phenotypes associated with 4 SMN2 copies. Methods Clinical phenotypes were analyzed in all the patients with 4 SMN2 copies as part of a nationwide effort including all the Italian pediatric and adult reference centers for spinal muscular atrophy (SMA). Results The cohort includes 169 patients (102 men and 67 women) with confirmed 4 SMN2 copies (mean age at last follow-up = 36.9 ± 19 years). Six of the 169 patients were presymptomatic, 8 were classified as type II, 145 as type III (38 type IIIA and 107 type IIIB), and 8 as type IV. The remaining 2 patients were asymptomatic adults identified because of a familial case. The cross-sectional functional data showed a reduction of scores with increasing age. Over 35% of the type III and 25% of the type IV lost ambulation (mean age = 26.8 years ± 16.3 SD). The risk of loss of ambulation was significantly associated with SMA type (p < 0.0001), with patients with IIIB and IV less likely to lose ambulation compared to type IIIA. There was an overall gender effect with a smaller number of women and a lower risk for women to lose ambulation. This was significant in the adult (p = 0.009) but not in the pediatric cohort (p = 0.43). Interpretation Our results expand the existing literature on natural history of 4 SMN2 copies confirming the variability of phenotypes in untreated patients, ranging from type II to type IV and an overall reduction of functional scores with increasing age.S.C.P., G.P.C., and E.M. are members of the European Reference Network for Rare Neuromuscular Diseases (ERN EURO-NMD). G.Coratti is funded by grant from the Italian Ministry of Health (GR-2021-12374579). E.M. is funded by grant from the Italian Ministry of Health (RF-2019-12370334). M.C.P. is funded by grant from the Italian Ministry of Health (GR-2018-12365706). E.P. is funded by grant from the Italian Telethon (GUP21008). The ITASMAC registry is partly funded by Biogen and Roche

Target Therapy in Cancer Treatment: mPGES-1 and PARP

Target therapy is an approach focusing on specific protein or signaling pathways. This therapy is directly aimed to a molecular target such as a receptor, growth factor or enzyme in cancer cells. These targets are used by the tumor cells themselves to obtain uncontrolled proliferation, resistance to traditional therapies and to increase the number of blood vessels in the tissue of origin (neoangiogenesis). A purpose of target therapy may be to counteract the growth and proliferation of cancer cells through the use of drugs or monoclonal antibodies capable of inhibiting the receptor for the epidermal growth factor (EGFR), that is crucial in the process of neo-angiogenesis, protein kinases (PKs), as regulators of cell growth signals and human epidermal growth factor type 2 (HER2), which is essential in stimulating growth and proliferation of cancer cells. Among anticancer drugs, Bevacizumab, a humanised monoclonal antibody produced by recombinant DNA technique, is used for the first-line treatment of metastatic breast cancer, as it inhibits EGFR and the vascular endothelial cell growth factor (VEGF). Abemaciclib, a protein kinase inhibitor drug, is also used for the treatment of the same cancer. In 20-30% of primary breast tumors, the excessive expression of HER2 is observed; thus, HER2 inhibitors may represent another plausible therapy. A potent HER2 inhibitor is the recombinant humanized igG1 monoclonal antibody Trastuzumab, which was first tested in 1992 and is currently used for the treatment of HER2 positive breast cancer. Unfortunately, despite the numerous advances in finding new therapies, patients treated with these drugs often suffer from severe undesirable side effects. Therefore, the search for new therapeutic targets may be desirable. In this paper we analyse particularly two targets studied quite recently: the microsomal prostaglandin E2 synthase type 1 (mPGES-1) and poly (ADP-ribose) polymerase (PARP) proteins

Target Therapy in Cancer Treatment: mPGES-1 and PARP

Target therapy is an approach focusing on specific protein or signaling pathways. This therapy is directly aimed to a molecular target such as a receptor, growth factor or enzyme in cancer cells. These targets are used by the tumor cells themselves to obtain uncontrolled proliferation, resistance to traditional therapies and to increase the number of blood vessels in the tissue of origin (neoangiogenesis). A purpose of target therapy may be to counteract the growth and proliferation of cancer cells through the use of drugs or monoclonal antibodies capable of inhibiting the receptor for the epidermal growth factor (EGFR), that is crucial in the process of neo-angiogenesis, protein kinases (PKs), as regulators of cell growth signals and human epidermal growth factor type 2 (HER2), which is essential in stimulating growth and proliferation of cancer cells. Among anticancer drugs, Bevacizumab, a humanised monoclonal antibody produced by recombinant DNA technique, is used for the first-line treatment of metastatic breast cancer, as it inhibits EGFR and the vascular endothelial cell growth factor (VEGF). Abemaciclib, a protein kinase inhibitor drug, is also used for the treatment of the same cancer. In 20-30% of primary breast tumors, the excessive expression of HER2 is observed; thus, HER2 inhibitors may represent another plausible therapy. A potent HER2 inhibitor is the recombinant humanized igG1 monoclonal antibody Trastuzumab, which was first tested in 1992 and is currently used for the treatment of HER2 positive breast cancer. Unfortunately, despite the numerous advances in finding new therapies, patients treated with these drugs often suffer from severe undesirable side effects. Therefore, the search for new therapeutic targets may be desirable. In this paper we analyse particularly two targets studied quite recently: the microsomal prostaglandin E2 synthase type 1 (mPGES-1) and poly (ADP-ribose) polymerase (PARP) proteins