YokoCo

Synaptic inhibition plays a crucial role in regulating neuronal excitability, which is the foundation of nervous system function. This inhibition is largely mediated by the neurotransmitters GABA and glycine that activate Cl-permeable ion channels, which means that the strength of inhibition depends on the Cl gradient across the membrane. In neurons, the Cl gradient is primarily determined by two secondarily-active cation-chloride cotransporters (CCCs), NKCC1 and KCC2. CCC-mediated regulation of the neuronal Cl gradient is critical for healthy brain function, as dysregulation of CCCs has emerged as a key mechanism underlying neurological disorders including epilepsy, neuropathic pain, and autism spectrum disorder. This Review begins with an overview of neuronal chloride transporters before explaining the dependent relationship between these CCCs, Cl regulation, and inhibitory synaptic transmission. We then discuss the evidence for how CCCs can be regulated, including by activity and their protein interactions, which underlie inhibitory synaptic plasticity. For readers who may be interested in conducting experiments on CCCs and neuronal excitability, we have included a section on techniques for estimating and recording intracellular Cl, including their advantages and limitations. While the focus of this Review is on neurons, we also examine how Cl is regulated in glial cells, which in turn regulate neuronal excitability through the tight relationship between this non-neuronal cell type and synapses. Lastly, we discuss the relatively extensive and growing literature on how CCC-mediated neuronal excitability contributes to neurological disorders.

Gastrointestinal (GI) polyposis is a rare condition in GI diseases. To date about 500 cases of Cronkhite-Canada syndrome (CCS) have been reported worldwide.

Infection with () can lead to disseminated disease involving the gastrointestinal tract presenting as diffuse abdominal pain and diarrhea which may mimic inflammatory bowel disease (IBD).

Hydrosalpinx is rare in childhood, and its pathogenesis may differ from that in reproductive-aged women. Herein, we report a case of hydrosalpinx in a premenarcheal 14-year-old girl, which might be caused by thickening of the smooth muscle of the fallopian tube. The patient had recurrent right lower abdominal pain and was referred to our hospital with a suspected adnexal tumor. Laparoscopy revealed a hydrosalpinx with complete obstruction of the fimbria and scar-like stenosis of the proximal ampulla. Right salpingectomy was performed because of a severe hydrosalpinx. As the patient was a virgin and a vaginal culture showed normal flora, ascending infection to the fallopian tube was not considered to be the cause of the hydrosalpinx. Histopathological examination revealed that the resected fallopian tube had a markedly dilated lumen with no inflammatory cell infiltration. Immunohistochemically, estrogen- and progesterone-positive smooth muscle proliferation was found at the isthmus of the fallopian tube.

Administration of a widely used 5-hydroxytryptamine receptor (5HT R) antagonist (ondansetron) potently inhibited the development of experimentally induced opioid dependence and withdrawal responses in mice and humans. However, in several studies examining withdrawal symptoms in subjects with chronic opioid use disorders (OUD), ondansetron exhibited reduced or absent efficacy. Since attenuation of opioid withdrawal symptomatology is mediated within the brain, this study examined single-dose ondansetron pharmacokinetics in the blood and brain of mice. We demonstrate that ondansetron concentrations in brain (C ng/mg) are 1000-fold lower than the blood concentrations (C ng/ml) and decrease rapidly after ondansetron administration; and that a large percentage of brain ondansetron remains in the ventricular fluid. These results indicate that the ondansetron dose, and the time window between ondansetron and opioid administration and when withdrawal is assessed are critical considerations for clinical studies involving subjects with chronic OUD. The pharmacokinetic results and the dosing considerations discussed here can be used to improve the design of subsequent clinical trials, which will test whether a more prolonged period of ondansetron administration can provide a desperately needed therapy that can prevent the development of the Neonatal Opioid Withdrawal Syndrome (NOWS) in babies born to mothers with chronic OUD.

Ehlers-Danlos syndromes (EDS) are a group of disorders characterized by abnormal connective tissue affecting several organ systems. Patients with the hypermobile type of EDS (hEDS) commonly experience chronic pain which can present as musculoskeletal pain, fibromyalgia, neuropathic pain or abdominal pain. The effective management of chronic pain in hEDS patients is a challenge. This study reviews two cases of chronic pain in hEDS patients and the multimodal treatment regimen used along with peripheral nerve stimulation for shoulder and knee pains, never before reported in hEDS patients. Since hEDS associated chronic pain is multifactorial in origin, treatment requires a multidisciplinary approach which includes physical therapy, psychotherapy, pharmacotherapy and interventional pain procedures such as trigger point injections, peripheral nerve block, radiofrequency ablation and peripheral nerve stimulation.

An 11-year-old, previously healthy boy presented to the emergency center (EC) for acute respiratory distress in the setting of 5 months of recurrent and worsening rash with progressive fatigue, shortness of breath, chest pain, and cough. At the onset of his rash, he and his younger brothers were diagnosed with roseola. Although his brothers' symptoms resolved, the patient's rash recurred, prompting his primary care provider to prescribe amoxicillin. The rash subsequently worsened, so amoxicillin was stopped; a prednisone course was prescribed which alleviated the rash. Upon completion of the prednisone course, the rash returned more diffusely with associated symptoms of shortness of breath, chest pain, and cough. Because of these symptoms, his mother brought him to the EC, where his vitals were notable for tachypnea and tachycardia. His initial EC imaging workup was remarkable for an echocardiogram with a mild to moderate circumferential pericardial effusion, chest x-ray (CXR) with a large right pleural effusion, and chest computerized tomography significant for prominent and diffuse mediastinal and hilar lymphadenopathy with numerous enlarged axillary lymph nodes. Laboratory results were notable for elevated liver enzymes, inflammatory markers, d-dimer, and brain natriuretic peptide. Differential diagnosis remained broad, including infectious, oncologic, and rheumatologic etiologies. Our panel of experts reviews the evaluation, hospital course, and treatment of this patient presenting with an unusual rash and serositis.

Enterococcal infections are increasingly common in hospitalized patients. Enterococcal meningitis/ventriculitis (EMV) is an extremely rare condition of enterococcal infections, particularly occurring in children. This study investigated the clinical and microbiological characteristics, predisposing factors, and prognosis in pediatric patients with EMV.

Now some reports have pointed out that calcimimetics agents is effective in the treatment of secondary hyperparathyroidism (SHPT) in chronic kidney disease (CKD) patients, but there is no detailed description of the advantages and disadvantages of calcimimetics agents of SHPT in CKD patients. We tried to pool the published data to verify the effectiveness of calcimimetics agents and to compare the advantages and disadvantages of cinacalcet compared with control in the treatment of SHPT in CKD patients.

To explore the effects of myofascial release (MFR) on pain and dysfunction in individuals with chronic mechanical neck pain (MNP).