Rejected

Diabetic peripheral neuropathic pain (DPNP) is a common manifestation of diabetic peripheral neuropathy (DPN). Although the pathogenesis of DPNP remains unclear, the disinhibition of spinal dorsal horn neuronal circuitry mediated by endoplasmic reticulum stress (ERS) is an important mechanism underlying neuropathic pain (NP). Tanshinone II A is mainly used to treat cardiovascular diseases but has also been shown to relieve various types of neuralgia, including DPNP. This study investigated the effects of tanshinone IIA in DPNP model rats. We divided animals into two groups: 1) the model (diabetic) group and 2) the tanshinone II A-treatment group. Our results demonstrated that diabetic rats exhibited a decrease in the mechanical withdrawal threshold (MWT) and thermal withdrawal latency (TWL), and that NMT is increased and TWL is prolonged in rats treated with tanshinone II A. Additionally, the levels of ERS-signaling pathway factors in the spinal dorsal horns of rats were lower in the tanshinone IIA-treated group than in the diabetic group. Overall, our study demonstrated that the disinhibition of spinal dorsal horn neuronal circuitry mediated by endoplasmic reticulum stress underlies DPNP and is modulated by tanshinone IIA treatment.

Treatment of neurological diseases using systemic and non-surgical techniques presents a significant challenge in medicine. This challenge is chiefly associated with the condensation and coherence of the brain tissue. The coherence structure of the brain is due to the presence of the blood brain barrier (BBB), which consists of a continuous layer of capillary endothelial cells. The BBB prevents most drugs from entering the brain tissue and is highly selective, permitting only metabolic substances and nutrients to pass through. Although this challenge has caused difficulties for the treatment of neurological diseases, it has opened up a broad research area in the field of drug delivery. Via the utilization of nanoparticles (NPs), nanotechnology can provide the ideal condition for passing through the BBB. NPs with suitable dimensions and optimum hydrophobicity and charge, as well as appropriate functionalization, can accumulate in the brain. Furthermore, NPs can facilitate the targeted delivery of therapeutics into the brain areas involved in Alzheimer's disease, Parkinson's disease, stroke, glioma, migraine, and other neurological disorders. This review describes these methods of actively targeting specific areas of the brain.

To report a case of a child with primary immunodeficiency who at eight years developed digestive symptoms, culminating with the diagnosis of a neuroendocrine tumor at ten years of age.

Pelvic inflammatory disease (PID) is a common infection which can result in severe long term morbidity, such as chronic pelvic pain and infertility. The morbidity increases in correlation to the number of PID events. Our study aim to assess the risk factors for recurrence of pelvic inflammatory disease.

Despite advances in medicine and numerous agents that counteract pain, millions of patients continue to suffer. Attention has been given to identify novel botanical interventions that produce analgesia by interacting with nociceptive-transducing channels. The aim of this review is to provide an overview of the actual knowledge of Acmella oleracea (L.) and its activities, particularly those that are anti-inflammatory, anti-oxidant, and painkiller. These activities are attributed to numerous bioactive compounds, such as phytosterols, phenolic compounds and N-alkylamides (spilanthol, responsible for many activities, primarily anesthetic). This review includes 99 eligible studies to consider the anti-inflammatory, anti-oxidant, and painkiller of Acmella. Studies reported in this review confirmed anti-inflammatory and anti-oxidant activities of Acmella, postulating that transcription factors of the nuclear factor-κB family (NF-κB) trigger the transcription iNOS and COX-2 and several other pro-inflammatory mediators, such as IL-6, IL-1β, and TNF-α. The antinociceptive effects has been demonstrated and have been related to different processes, including inhibition of prostaglandin synthesis, activation of opioidergic, serotoninergic and GABAergic systems, and anesthetic activity through blockage of voltage-gated Na Channels. acmella oleracea represents a promise for pain management, particularly in chronic degenerative diseases, where pain is a significant critical issue.

Eicosanoids like leukotrienes and prostaglandins that produced within the arachidonic acid cascade are involved in the pathogenesis of pain, acute and chronic inflammatory diseases. A promising approach for an effective anti-inflammatory therapy is the development of inhibitors targeting more than one enzyme of this cascade. Aiming to develop balanced COX/LOX inhibitors; 4-aminosalicylate based thiazolinones having different substituents at the 5th position of the 4-thiazolinone ring (2-22) were designed, synthesized, characterized and evaluated in vitro and in vivo for their anti-inflammatory activity. Most of the investigated compounds showed high COX-2 inhibitory potencies (IC 39-200 nM) with selectivity indexes (30-84). Two compounds, 19 and 21, (IC = 41 and 44 nM), are equipotent to celecoxib (IC = 49 nM), while compound 22 (IC = 39 nM) was the most potent. For 15-LOX, compounds 5, 11, 19, 21 and 22 revealed higher potency (IC 1.5-2.2 µM) than zileuton (IC 15 µM). Thus, compounds 5, 11, 19, 21 and 22 are potent dual inhibitors of COX-2 and 15-LOX. In vivo anti-inflammatory testing of these compounds revealed that, compounds 5 and 21 had an anti-inflammatory activity similar to indomethacin and celecoxib (% inhibition of oedema = 60 ± 9) and higher than diclofenac potassium (% inhibition = 52 ± 29), while compound 22 (% inhibition = 63 ± 5) was more active than the reference drugs. The results showed that the activity is controlled by the bulkiness and lipophilicity of the substituent at the 5th position. The cytotoxicity results revealed that all compounds are not cytotoxic, additionally, in an experimental model of ulcerogenic effect, the most active compounds 21 and 22 showed better safety profile than indomethacin. Further, at the active sites of the COX-1, COX-2 and 15-LOX co-crystal, 19, 21, and 22 showed high binding forces in free binding energy study, which is consistent with in vitro and in vivo results. In conclusion, these compounds are good candidates for further biological investigation as potential anti-inflammatory drugs with dual balanced inhibition of COX and 15-LOX and good safety profile.

Nitrous oxide (N O) is frequently used for short anaesthesia/analgesia in children undergoing painful or repetitive procedures . Children with acute lymphoblastic leukaemia (ALL) require repeated lumbar punctures with direct instillation of intrathecal chemotherapy, usually the anti-folate agent Methotrexate, during their treatment. These procedures are frequently performed under anaesthesia. Concerns have been intermittently raised about a drug-interaction between methotrexate and N O that may potentiate the undesirable side effects of methotrexate, including neurotoxicity. However, the clinical evidence consists mainly of isolated case reports leading to a lack of consensus amongst paediatric anaesthetists about the relative risk-benefits of using N O in children with ALL. In this article, we review the biochemical basis and scientific observations that suggest a significant interaction between N O and methotrexate due to their dual inhibition of the key enzyme methionine synthase. The possible role of this interaction in potentiating neurotoxicity in children with cancer is discussed, and arguments and counter-arguments about the clinical significance of this largely theoretical relationship are explored. Following comprehensive review of all the available data we make the case for the circumstantial evidence being sufficiently compelling to prompt a review of practice by paediatric anaesthetists and call for a precautionary approach by avoiding the use of N O in children receiving concurrent methotrexate.

Persistent pain is a known challenge among breast cancer survivors. In secondary analyses of a randomized controlled trial, we examined the effect of progressive resistance training on persistent pain in the post-operative year in women treated for breast cancer with axillary lymph node dissection.

Cervical artery dissection is an acute arterial disease. Although it is not a common disease, 40-60% cerebral infarction and 20-30% transient ischemic attack could be seen. Thus, cervical artery dissection is important to recognize. Fifty-three years old female patient consulted with head, neck and face endaural pain that started after than spread directly left face half, effect of sometimes orbita and sometimes submaxillary area, occasionally accompanied by redness in the eye, extending from a few minutes to a few hours, it has been sharp and pulsatil characteristics and she never experienced before similar. Although not typical, with the initial diagnosis was trigeminal neuralgia and cluster headache (CH), carbamazepine and tramadol treatment were started. The patient who had neck pain was severe during USG, and with atypical features was BT angioed to the brain and neck concerning differential diagnosis of the patient. It was detected profile compatible with dissection at left ICA proximal. In the literature, there are rare cases of ICA dissection mimicking CH and other trigeminal autonomic cephalalgias. A common recommendation in CH case reports is the need for neurovascular imaging in cases with atypical features.