Rejected

Since the year 2000, over 413,000 service members have sustained traumatic brain injury (TBI) and may present with post-concussive sequelae including headaches, fatigue, irritability, cognitive problems, depression, insomnia, and chronic pain. Although the focus of the article is on military TBI, the usefulness of S-adenosylmethionine (SAMe) would extend to both civilian and military populations. This narrative review examines the preclinical and clinical literature of SAMe's metabolism and alterations seen in disease states such as depressive disorders, pain disorders, fatigue, cognition, dementia, use in pregnancy and peripartum, children, adolescents, and adults, to the elderly with and without dementia, stroke, and neurodegeneration, in order to highlight its potential benefit in post-concussive sequelae after TBI.

To observe the effect of electroacupuncture (EA) on the expression of Pirt (a regulator of TRPV1) in the dorsal root ganglia (DRG) and transient receptor potential vanilloid 1 (TRPV1, a molecular sensor of noxious heat and capsaicin) in the colonic mucosa in rats suffering from diarrhea-predominant irritable bowel syndrome (IBS-D), so as to explore its mechanisms underlying alleviation of visceral hypersensitivity of IBS-D.

Despite the availability of many anti-pain drugs, in the form of NSAIDs, steroids, gabapentinoids, opioids, and antidepressants, in this study we address the natural compounds belonging to the group of Mexican medicinal plants or "Mexican folk medicine", used for pain management in Mexico. Our interest in this subject is due to the growing idea that "natural is harmless" and to the large number of side effects exhibited in pharmacotherapy. The objective of this review was to document the scientific evidence about Mexican medicinal plants and their derivatives used for inflammatory and neuropathic pain treatment, as well as the mechanisms of action implicated in their antinociceptive effects, their possible adverse effects, and the main pharmacological aspects of each plant or compound. Our data review suggested that most studies on Mexican medicinal plants have used inflammatory experimental models for testing. The anti-pain properties exerted by medicinal plants lack adverse effects, and their toxicological assays report that they are safe to consume; therefore, more studies should be performed on preclinical neuropathic pain models. Moreover, there is no convincing evidence about the possible mechanisms of action involved in the anti-pain properties exerted by Mexican plants. Therefore, the isolation and pharmacological characterization of these plant derivatives' compounds will be important in the design of future preclinical studies.

The objective of this study was to determine the reasons for complaints and describe the judicial means upstream of France's courts following arthroscopy.

Interstitial Cystitis or Bladder Pain Syndrome (IC/BPS) is a heterogeneous condition characterized by elevated levels of inflammatory cytokines, IL-1β, IL-6, IL-8, IL-10, TNF-α, and is associated with debilitating symptoms of pelvic pain and frequent urination. A standard of care for IC/BPS has not been established, and most patients must undergo a series of different treatment options, with potential for severe adverse events. Here, we report a patient with a 26-year history of IC/BPS following treatment with multiple therapies, including low doses of etodolac, amitriptyline and gabapentin, which she was unable to tolerate because of adverse effects, including headaches, blurred vision and cognitive impairment. The patient achieved a complete clinical remission with minimal adverse events after 16 cycles of -acetylcysteine (NAC) intravenous (IV) infusions over a period of 5 months, and pro-inflammatory cytokine levels were reduced when compared to measurements taken at presentation. Personalized low dose NAC IV infusion therapy represents an effective, safe, anti-inflammatory therapy administered in the outpatient setting for IC/BPS, and warrants further investigation.

Migraine is an invalidating neuro-vascular disorder largely spread in the world population. Currently, its pathophysiology is not yet completely understood. The purpose of this study was to investigate the urinary proteome of women suffering from menstrually related migraine (MM) and post-menopause migraine (PM) in comparison with non-headache women as controls, to search potential biomarkers of these migraine sub-types. Urine samples were analyzed by mono-dimensional gel electrophoresis (SDS-PAGE) and two-dimensional gel electrophoresis (2DE) coupled to liquid chromatography-mass spectrometry (LC-MS/MS). Twenty-one urinary proteins were found significantly dysregulated in MM and PM ( < 0.05). The STRING Analysis database revealed interaction between 15 proteins, which were mainly involved in the immune and inflammatory response. Seven of the most considerable proteins were further quantified by western blot: protein S100A8 (S10A8), up-regulated in MM, uromodulin (UROM), alpha-1-microglobulin (AMBP), gelsolin (GELS), prostaglandin-H2 D-isomerase (PTGDS), over-expressed in PM, apolipoprotein A-I (APOA1), and transthyretin (TTHY), respectively down- and up-regulated in both migraineur groups vs controls. These candidate biomarkers might be involved in the neurophysiological network of MM and PM, thus helping to better understand the pathophysiology of these migraine forms. If validated in large-scale studies, this protein cluster could become a distinctive target for clinical applications in migraine diagnosis and treatment.

This study aimed to assess the clinical and radiographic outcomes of juvenile patients who suffered from stage II or III osteochondritis dissecans (OCD) of the knee and underwent arthroscopic retrograde drilling and internal fixation with bioabsorbable pins.

Peritoneal metastases of hepatocellular carcinoma (HCC) are occasionally observed, but rupture of such metastases is rare. We report a resected case with a single ruptured peritoneal HCC metastasis. A 57-year-old man with chronic hepatitis C underwent hepatic resection twice for hepatocellular carcinoma. Recurrence in S3 was found, and the tumor was treated by radiofrequency ablation therapy (RFA). One month after RFA, plane computed tomography (CT) showed a nodule with a diameter of 5 cm near the upper pole of the spleen, and the serum alpha-fetoprotein (AFP) level remained high. The patient was admitted to hospital, with a chief complaint of abdominal pain 4 days after the CT scan, and diagnosed with intra-abdominal hemorrhage caused by a ruptured peritoneal HCC metastatic nodule. We performed semi-urgent surgery, including splenectomy and peritoneal metastasis resection, and the patient was discharged on the 10th postoperative day. Histopathological examination of the nodule confirmed HCC metastasis. The patient is alive with no evidence of recurrence as of 1 year and 6 months after the operation, with AFP levels remaining within the normal range.

It has been shown that a high acid load in the human body can affect inflammatory factors and the nitric oxide pathway. These factors are also thought to play an important role in the initiation of migraine attacks. We have therefore explored the association between dietary acid load and odds of migraine in a case-control study.

Possible involvement of μ- and κ-opioid receptors and cannabinoid type 1 receptors (CB1) into the mechanism of analgesic activity of the experimental drug product "Thiowurtzine, (capsule 120 mg)" synthesized on the basis of active pharmaceutical substance 4-(3,4-dibromthiophencarbonyl)-2,6,8,12-tetraacethyl-2,4,6,8,10,12hexaazatetracyclo [5,5,0,0,0]dodecane was studied in vivo using the hot plate test and acetic acid writhing test. The involvement of κ-opioid receptors and noninvolvement of μ-receptors and CB1 receptors in the mechanism of thiowurtzine analgesia were demonstrated. The mechanism of interaction of the test analgesic with opioid receptors differs from that of the reference drug tramadol. The interaction of thiowurtzine with serotonergic, GABAergic, and muscarinic cholinergic neurotransmitter systems was studied in vivo using pharmacological analyzers. The absence of muscarinic cholinolytic effect of thiowurtzine was demonstrated in the model of arecoline-induced tremor. The central serotonin-blocking activity of the analgesic was revealed in the model of 5-hydroxytryptophan hyperkinesis in mice. Anticonvulsant activity was demonstrated in the corazol convulsions test, which attested to the presence of a GABAergic component. The mechanism of central analgesia caused by the drug product "Thiowurtzine, capsule 120 mg" appeared to be polymodal. The antinociceptive activity of the analgesic was comparable to that of tramadol.