Rejected

Chikungunya fever is a disease caused by the Chikungunya virus (CHIKV) that is transmitted by the bite of the female of sp. mosquito. The symptoms include fever, muscle aches, skin rash, and severe joint pains. The disease may develop into a chronic condition and joint pain for months or years. Currently, there is no effective antiviral treatment against CHIKV infection. Treatments based on natural compounds have been widely studied, as many drugs were produced by using natural molecules and their derivatives. Alpha-phellandrene (α-Phe) is a naturally occurring organic compound that is a ligand for ruthenium, forming the organometallic complex [RuCl(p-cymene)] (RcP). Organometallic complexes have shown promising as candidate molecules to a new generation of compounds that presented relevant biological properties, however, there is a lack of knowledge concerning the anti-CHIKV activity of these complexes. The present work evaluated the effects of the RcP and its precursors, the hydrate ruthenium(III) chloride salt (RuCl⋅xHO) (Ru) and α-Phe, on CHIKV infection . To this, BHK-21 cells were infected with CHIKV- (CHIKV), a viral construct harboring the reporter gene, at the presence or absence of the compounds for 16 h. Cytotoxicity and impact on infectivity were analyzed. The results demonstrated that RcP exhibited a strong therapeutic potential judged by the selective index > 40. Antiviral effects of RcP on different stages of the CHIKV replicative cycle were investigated; the results showed that it affected early stages of virus infection reducing virus replication by 77% at non-cytotoxic concentrations. Further assays demonstrated the virucidal activity of the compound that completely blocked virus infectivity. molecular docking calculations suggested different binding interactions between aromatic rings of RcP and the loop of amino acids of the E2 envelope CHIKV glycoprotein mainly through hydrophobic interactions. Additionally, infrared spectroscopy spectral analysis indicated interactions of RcP with CHIKV glycoproteins. These data suggest that RcP may act on CHIKV particles, disrupting virus entry to the host cells. Therefore, RcP may represent a strong candidate for the development of anti-CHIKV drugs.

In Africa, postoperative pain management is still a major problem with a prevalence of postoperative pain in up to 95.2% of the patients. There are little data on the prevalence and potential risk factors for postoperative pain in Tanzania. Therefore, we aimed to investigate these at Kilimanjaro Christian Medical Centre in Northern Tanzania. Our goal is to optimize pain management.

Malignant triton tumors (MTT) are rare but highly aggressive tumors that originate from the Schwann cells. These tumors can occur in any part of the body, mostly present late and carry poor prognosis.

Metformin (biguanide) is a drug widely used for the treatment of type 2 diabetes. This drug has been used for 60 years as a highly effective antihyperglycemic agent. The search for the mechanism of action of metformin has produced an enormous amount of research to explain its effects on gluconeogenesis, protein metabolism, fatty acid oxidation, oxidative stress, glucose uptake, autophagy and pain, among others. It was only up the end of the 1990s and beginning of this century that some of its mechanisms were revealed. Metformin induces its beneficial effects in diabetes through the activation of a master switch kinase named AMP-activated protein kinase (AMPK). Two upstream kinases account for the physiological activation of AMPK: liver kinase B1 and calcium/calmodulin-dependent protein kinase kinase 2. Once activated, AMPK inhibits the mechanistic target of rapamycin complex 1 (mTORC1), which in turn avoids the phosphorylation of p70 ribosomal protein S6 kinase 1 and phosphatidylinositol 3-kinase/protein kinase B signaling pathways and reduces cap-dependent translation initiation. Since metformin is a disease-modifying drug in type 2 diabetes, which reduces the mTORC1 signaling to induce its effects on neuronal plasticity, it was proposed that these mechanisms could also explain the antinociceptive effect of this drug in several models of chronic pain. These studies have highlighted the efficacy of this drug in chronic pain, such as that from neuropathy, insulin resistance, diabetic neuropathy, and fibromyalgia-type pain. Mounting evidence indicates that chronic pain may induce anxiety, depression and cognitive impairment in rodents and humans. Interestingly, metformin is able to reverse some of these consequences of pathological pain in rodents. The purpose of this review was to analyze the current evidence about the effects of metformin in chronic pain and three of its comorbidities (anxiety, depression and cognitive impairment).

Osteochondritis dissecans (OCD) of the capitellum is a leading cause of elbow disability in adolescent baseball players. Previous studies have not found an association of player position with capitellar OCD. Elbow pain and a longer playing history might be related to progression of capitellar OCD but do not in themselves increase the risk of development of the condition. The cause of capitellar OCD is likely to include a combination of repetitive microtrauma and internal factors, such as ischemia and genetic predisposition. A combination of radiography, computed tomography, magnetic resonance imaging, and ultrasonography have aided our understanding of the pathology of capitellar OCD. Screening using ultrasonography enables early detection and provides an opportunity for successful conservative treatment. Treatment has conventionally included both operative and nonoperative measures based on the stage and size of the lesion, skeletal maturity, subjective symptoms, and structural integrity of the cartilage. Early-stage lesions respond better to nonoperative treatment than those in more advanced stages. Operative indications include persistent symptoms despite nonoperative treatment, symptomatic loose bodies, and displacement or detachment of fragments. J. Med. Invest. 67 : 217-221, August, 2020.

Ultrasound-guided cervical nerve root block is the technique of injecting local anesthetic or steroid into the intertubercular groove outside of the cervical foramen under real-time ultrasound guidance. It has established diagnostic and therapeutic employment for patients suffering symptoms caused by cervical disc disorders and foraminal stenosis. Measures of selective nerve root blockade would have vital clinical utility, especially in multilevel disease or combined with atypical symptoms, where subjective assessment is difficult. This case reported a 47-year-old male patient who suffered from severe radicular pain confined to the index and middle fingers, with weakness of the right upper extremity. He was successfully treated with selective C6, C7 nerve root under ultrasound guidance. For confirmation of the proper analgesia range, laser speckle contrast imaging (LSCI) and infrared thermography (IT) were both constructed over the dorsum of the hands and forearms during the procedure. The results of the off-line analysis suggested LSCI and IT might be considered as alternative measurements for the selective cervical nerve root.

Identifying opioid use disorder (OUD) in patients prescribed opioid therapy for chronic pain is challenging but critically important. Patients may have multiple reasons for taking medications, which they may not reveal if not properly interviewed. In this study, modified Drug Effects Questionnaires (DEQ) were used to assess the liking of and desire to take prescription opioids both for reasons of pain relief and for reasons excluding pain relief. We hypothesized patients would more strongly endorse their medications for reasons of pain relief compared to reasons excluding pain relief, and patients who endorse medications for reasons excluding pain relief may be at higher risk of developing OUD.

Paracetamol with ibuprofen or with naproxen are frequently prescribed by doctors in combination. It was found that patients using a combination of NSAID like acetaminophen and ibuprofen experienced less pain. Patients are more compliant if these two drugs are combined in an ester form and given in one dosage form. The esterified prodrugs are hydrolyzed in humans to their active forms. In this study, two esters of paracetamol combined with ibuprofen and naproxen were synthesized as prodrugs. The physiochemical properties of these products were identified. Moreover, the bioactivities of these prodrugs were tested for its anti-inflammatory and anticoagulant activities. The results showed an improved COX inhibition and anticoagulant activity compared with their parent drugs. The synthesized drugs are expected to improve patient's compliance in terms of administration frequency and will have better pharmacokinetic properties with fewer side effects.

The adverse reaction of Black Hairy Tongue (BHT) caused by linezolid is rare. We reports a case of linezolid-induced BHT, and reviews relevant literatures at home and abroad. It aims to provide a safe and reasonable basis for clinical medication use. A 14-year-old adolescent with pneumonia caused by methicillin-resistant (MRSA) developed a rash and pruritus due to Vancomycin. Instead, the patient was given linezolid 600mg q12h in injection during hospitalization and in tablet after discharge. On the 14th day after injection and the second day after oral administration the patient showed BHT without other abnormal taste symptoms. But all the symptoms could be tolerated and he completed the therapy course of linezolid. Tongue symptoms completely disappeared on the 8th day after drug withdrawal. Based on the Karch and Lasagna evaluation methods and the cause-and-effect evaluation methods of the WHO collaborating center for international adverse drug reaction (ADR) monitoring, it is likely that this patient had a BHT caused by linezolid. The mean time of occurrence of BHT was 14.36 days, and the mean time of symptom disappearance was 23.43 days after drug administration. When linezolid is prescribed to patients, especially those with atopy, the patient's tongue should be closely observed and good oral hygiene is recommended.

Diabetic neuropathic pain (DNP) is one of the common complications in type 2 Diabetes Mellitus (DM) patients. However, molecular mechanisms in underlying diabetic neuropathic pain are still poorly understood. Kalirin-7, a multifunctional Rho GDP/GTP exchange factor, located at the excitatory synapses, was reported to modulate the neuronal cytoskeleton. Therefore, in this study, we explored the effects of Kalirin-7 on type 2 diabetic neuropathic pain and the mechanisms in spinal cord in rats.