Melanoma Differentiation-Associated Gene 5 Regulates the Expression of a Chemokine CXCL10 in Human Mesangial Cells: Implications for Chronic Inflammatory Renal Diseases

Mesangial cells play an important role in inflammatory reactions in kidney. Although viral infections often trigger the worsening of chronic inflammatory renal diseases, the mechanisms are largely unknown. Melanoma differentiation-associated gene 5 (MDA5) is a member of RNA helicase family with a conserved Asp-Glu-x-His (DExH) box. In the present study, we examined the effect of polyinosinic-polycytidylic acid (poly IC), an authentic double-stranded RNA (dsRNA) that mimics viral dsRNAs, on MDA5 expression using primary culture of human mesangial cells. The cells were simply treated or transfected with poly IC; the former procedure is a model of cells exposed to viral dsRNA released from dying cells, and the latter is a model of entry of RNA virus into the cytoplasm. Expression levels of MDA5 mRNA in mesangial cells were increased about 70-100 fold in response to either treatment or transfection with poly IC. MDA5 protein expression was significantly induced as well. RNA interference experiments revealed that poly IC treatment induced MDA5 expression via Toll-like receptor 3 (TLR3) and interferon (IFN)-β, and that poly IC trasnfection induced MDA5 expression via another DExH box RNA helicase, retinoic acid-inducible gene-I (RIG-I), and IFN-β. Moreover, MDA5 induced by poly IC, in turn, increased the expression of a chemokine CXCL10. In addition, immunohistochemical staining demonstrated a high level of MDA5 expression in glomeruli, mainly in mesangial cells, of patients with severe lupus nephritis or proteinuric IgA nephropathy. MDA5 may be involved not only in physiological antiviral reactions but also in chronic inflammation in glomerular mesangial cells.     

Pralidoxime inhibits paraoxon-induced depression of rocuronium-neuromuscular block in a time-dependent fashion

Objective

The composite effects of organophosphorus (OP)–cholinesterase (ChE) inhibitors and oximes on the actions of nondepolarizing neuromuscular blockers in acute OP-ChE inhibitor intoxication have not been evaluated in detail. We investigated the effects of paraoxon (Pox) (an OP-ChE inhibitor) and pralidoxime (PAM) (an oxime) on the nondepolarizing neuromuscular blocking action of rocuronium.

Methods

Isometric twitch tensions of rat left phrenic nerve-hemidiaphragm preparations elicited by indirect (phrenic nerve) supramaximal stimulation at 0.1 Hz were evaluated. Analysis of variance with post hoc testing was used for statistical comparison, and P < .05 was accepted as significant.

Results

Rocuronium reduced the indirectly elicited twitch tensions in normal (50% inhibitory concentration [IC₅₀], 9.84 [9.64-10.04] μM, mean [95% confidence interval]) and all pretreated diaphragms (P < .01, n = 6) in a concentration-dependent fashion. Paraoxon caused a rightward shift in the rocuronium concentration–twitch tension curve (IC₅₀, 15.48 [15.24-15.72] μM). The rightward shift was completely inhibited by previous copretreatment (IC₅₀, 9.98 [9.77-10.20] μM) and partially inhibited by simultaneous copretreatment (IC₅₀, 11.68 [11.45-11.91] μM) with PAM but was not inhibited by subsequent copretreatment (IC₅₀, 13.69 [13.39-13.99] μM) with PAM (P < .01, n = 6). Atropine did not influence the rightward shift (P < .01, n = 6).

Discussion

Paraoxon depressed rocuronium-induced neuromuscular block by inhibiting ChEs, and the action of Pox was inhibited by PAM. Pralidoxime acts more intensely when applied earlier. The time-dependent effect of PAM indicates that the preceding presence of PAM in proximity to ChEs before Pox is necessary for definite suppression of the Pox-induced ChE inhibition.     

Severe intrinsic acute kidney injury associated with therapeutic doses of acetaminophen

Acetaminophen is a commonly used medication to manage fever and pain in children and the drug is generally considered to be safe when used at appropriate therapeutic dosages. Recently, we encountered the case of a 3‐year‐old Japanese girl who suffered from severe intrinsic acute kidney injury (AKI) after therapeutic doses of acetaminophen for a fever due to viral infection. Renal biopsy indicated severe acute tubular necrosis with a significant striped interstitial fibrosis and mild interstitial inflammation. Unfortunately, she developed chronic kidney disease thereafter. This is the youngest case of biopsy‐proven severe intrinsic AKI associated with therapeutic doses of acetaminophen. Acetaminophen, even if administered at therapeutic dosages, may be dangerous in selected children, especially with possible pre‐existing volume depletion.     

Successful resuscitation for cardiac arrest due to severe accidental hypothermia accompanied by mandibular rigidity: a case of cold stiffening mimicking rigor mortis

Background

In cases of severe accidental hypothermia, it was recommended that resuscitation should be continued until the patient has rewarmed, as hypothermia itself can preserve cerebral function, and hypothermic cardiac arrest is reversible. During cardiopulmonary resuscitation for normothermic patients, muscle rigidity suggests the initiation of postmortem changes such as rigor mortis and can lead to the termination of resuscitation. Currently, the prognosis of cardiac arrest due to severe accidental hypothermia accompanied by rigidity is unknown.

Case presentation

A 29-year-old woman was found unresponsive near a snowy mountain trail. Upon discovery, she was found to be in cardiac arrest with an initial asystole rhythm and exhibited mandibular rigidity. On admission, her core temperature was 22 °C. Although cardiac arrest continued, and she showed no response to normal resuscitation, blood gas analysis revealed that her initial serum potassium level was 5.4 mmol/L. Extracorporeal membrane oxygenation (ECMO) for systemic perfusion and rewarming was initiated. After ECMO was introduced, return of spontaneous circulation was achieved. She showed no neurological impairments at discharge.

Conclusions

Muscle rigidity does not rule out the possibility of resuscitation in patients with severe accidental hypothermia under cardiac arrest. Serum potassium levels may assist in deciding whether ECMO should be introduced, even if a patient is in asystole. This knowledge may help emergency physicians to save the lives of such patients.

     

Ultrasound-guided supraclavicular central venous catheterization in patients with malignant hematologic diseases

We present two cases of central venous catheterization (CVC) in which an ultrasound-guided in-plane approach was used. Case 1 was a 60-year-old man with acute myelogenous leukemia in whom a right supraclavicular CVC was performed. He had pancytopenia (leukocytes 2,000/μL; erythrocytes 350 × 10⁴/μL; platelets 5.6 × 10⁴/μL), and abnormal coagulability (prothrombin time–international normalized ratio 1.35). A linear array transducer was positioned cephalad to the right clavicle and rotated 30° clockwise. The 21-gauge needle was manipulated from outside of the transducer. A CV catheter (CV legaforce EX^®; Terumo Co., Japan) was placed and stitched near the right clavicle. The patient felt no discomfort caused by the catheter. Case 2 was a 64-year-old women with malignant lymphoma whose right internal jugular vein was surrounded by abnormally enlarged lymph nodes. CVC was performed by the in-plane supraclavicular approach, avoiding puncture of the lymph node. This novel CVC technique is useful to minimize the risk of complications and patient discomfort by indwelling catheter.     

Development of an algorithm to predict comfort of wheelchair fit based on clinical measures

[Purpose] The purpose of this study was to develop an algorithm to predict the comfort of a subject seated in a wheelchair, based on common clinical measurements and without depending on verbal communication. [Subjects] Twenty healthy males (mean age: 21.5 ± 2 years; height: 171 ± 4.3 cm; weight: 56 ± 12.3 kg) participated in this study. [Methods] Each experimental session lasted for 60 min. The clinical measurements were obtained under 4 conditions (good posture, with and without a cushion; bad posture, with and without a cushion). Multiple regression analysis was performed to determine the relationship between a visual analogue scale and exercise physiology parameters (respiratory and metabolism), autonomic nervous parameters (heart rate, blood pressure, and salivary amylase level), and 3D-coordinate posture parameters (good or bad posture). [Results] For the equation (algorithm) to predict the visual analogue scale score, the adjusted multiple correlation coefficient was 0.72, the residual standard deviation was 1.2, and the prediction error was 12%. [Conclusion] The algorithm developed in this study could predict the comfort of healthy male seated in a wheelchair with 72% accuracy.Key words: Wheelchair seating, Posture maintenance, Multivariate analysis