The involvement of KATP channels in morphine‐induced antinociception and hepatic oxidative stress in acute and inflammatory pain in rats

This study investigated the role of K_ATP channels in morphine‐induced antinociception and hepatic oxidative stress in acute and inflammatory pain. The K_ATP channel modulators (K_ATP channel opener, diazoxide 100 mg/kg, p.o, and K_ATP channel blocker, glibenclamide, 3 mg/kg i.p.) were administered with morphine (80 mg/kg, i.p.). Antinociception was assessed by the tail‐flick and formalin tests in rats and measured by the area under the curve values and the maximum percent effect for 3 h. The indices of hepatic oxidative stress: glutathione, glutathione peroxidase, and malondialdehyde were then determined in the liver homogenates obtained from the treated animals. In both tests, glibenclamide antagonized morphine‐induced antinociception, whereas diazoxide augmented it in the tail‐flick test only. In the formalin test, glibenclamide alone has a significant hyperalgesic effect, whereas diazoxide decreased the number of flinches. Coadministration of glibenclamide with morphine antagonized the hepatotoxic effect of morphine in both animal models. In the tail‐flick test, glibenclamide administered alone significantly increased malondialdehyde's level. Coadministration of diazoxide with morphine increased glutathione level in the formalin test. Diazoxide administered alone exacerbated the hepatic oxidative stress in both animal models. These findings suggest a role of K_ATP channel modulators on morphine‐induced antinociception and hepatic oxidative stress. The administration of glibenclamide may prevent morphine‐induced hepatotoxicity. The effectiveness of diazoxide in the management of pain is limited due to its deleterious effect on the liver. However, the interaction of the K_ATP channel modulators with morphine depends on the differential sensitivity to the pain stimulus.     

An enzyme-linked immunosorbent assay for detection of IgG1 antibodies specific to human cystic echinococcosis in Egypt

Human cystic hydatidosis (cystic echinococcosis) is a chronic zoonotic disease that results from infection with the dog tapeworm Echinococcus granulosus. In Egypt, cystic echinococcosis (CE) is recognized in slaughtered livestock by veterinarians, however, there is little information about human CE infection rates. We describe an immunological assay useful for the diagnosis of human cystic hydatidosis. Sera were collected from surgically confirmed hydatid cases (34), nonendemic subjects free from parasitic infection (20) and from subjects (109) infected with other helminths (Hymenolepis nana, Schistosoma mansoni, Fasciola hepatica and Ancylostoma duodenale). Hydatid cyst fluid (HCF) of camel origin was used as antigen in an ELISA format to measure total E. granulosus specific IgG antibodies and IgG subclasses. Sensitivity measurements of total IgG, and IgG1-4 were 100, 100, 79.4, 61.8 and 55.9%, respectively, whereas respective specificity reached 65.1, 97.7, 98.4, 96.1 and 83. 7%. The diagnostic value of measuring IgG1 (97.7%), as assessed by a rating index (J) for combined sensitivity and specificity, was superior to total IgG (65.1%) and IgG2-4 (77.8, 57.9 and 39.6%, respectively). These findings set the stage for field evaluation of the IgG1 assay in areas endemic with human cystic hydatidosis.     

Agreement of tricuspid annular systolic excursion measurement between transthoracic and transesophageal echocardiography in the perioperative setting

Objective

The aim of our study was to evaluate the level of agreement between tricuspid annular plane systolic excursion (TAPSE) measured by transthoracic echocardiography (TTE) and TAPSE measured using transesophageal echocardiography (TEE) in anesthetized patients.

Materials and methods

Thirty patients scheduled for elective cardiac surgery were prospectively studied. Shortly after induction of anesthesia before the operation, TAPSE was measured by TTE using M-mode in apical 4chamber view (4CH) and by TEE in six different views: using 2D echocardiography in midesophageal (ME) 4CH view, using M-mode in deep transgastric right ventricle (dTG RV) view at 0° and dTG RV longaxis view (LAX) as well as using anatomical M-mode (AM-mode) in ME 4CH, dTG RV at 0° and dTG RV LAX views.

Results

Bland–Altman analysis showed a good agreement for TAPSE measured using M-mode in TTE and using AM-mode in TEE in the ME 4CH and dTG RV at 0° views (?2.5?±?18 and ?2.2?±?14% respectively). The agreement between TAPSE measured in TTE and TEE using 2D in ME 4CH, using M-mode in dT GRV 0° and using M-mode and AM-mode in dTG RV LAX view showed a significant systematic underestimation of the measurements (?8.8?±?21, ?8.8?±?24, ?17.8?±?28 and ?6.4?±?20%).

Conclusion

Our study showed that the right ventricular function can be accurately and precisely estimated using TAPSE measurement by TEE in the midesophageal four chamber and deep transgastric right ventricle view at 0° using anatomical M-mode.

     

The importance of correctly timing cancer immunotherapy

Introduction: The treatment options for cancer—surgery, radiotherapy and chemotherapy—are now supplemented with immunotherapy. Previously underappreciated but now gaining strong interest are the immune modulatory properties of the three conventional modalities. Moreover, there is a better understanding of the needs and potential of the different immune therapeutic platforms. Key to improved treatment will be the combinations of modalities that complete each other’s shortcomings.

Area covered: Tumor-specific T-cells are required for optimal immunotherapy. In this review, the authors focus on the correct timing of different types of chemotherapeutic agents or immune modulators and immunotherapeutic drugs, not only for the activation and expansion of tumor-specific T-cells but also to support and enhance their anti-tumor efficacy.

Expert opinion: At an early phase of disease, clinical success can be obtained using single treatment modalities but at later disease stages, combinations of several modalities are required. The gain in success is determined by a thorough understanding of the direct and indirect immune effects of the modalities used. Profound knowledge of these effects requires optimal tuning of immunomonitoring. This will guide the appropriate combination of treatments and allow for correct sequencing the order and interval of the different therapeutic modalities.     

Prednisone dosing per body weight or body surface area in children with nephrotic syndrome—is it equivalent?

The current guidelines recommend a dosage of prednisone of 60 mg/m² body surface area per day (BSA PRED) for the initial therapy of nephrotic syndrome (NS). Alternatively, a dosage of 2 mg/kg body weight per day (W PRED) can be used. We hypothesized that the BSA PRED and W PRED are not equivalent and analyzed the differences between BSA PRED calculated with various formulas for body surface area (BSA), W PRED and the dose of prednisone prescribed for our patients. We performed a retrospective chart review of the patients at their initial presentation of NS. Thirty-three children were included, of median age 3.34 years at presentation. The W PRED was significantly lower than BSA PRED (P < 0.05), with a median W PRED:BSA PRED ratio of 0.85 [interquartile range (IQR) 0.8 to 0.9]. The difference between W PRED and BSA PRED decreased proportionally to patients’ weights up to 30 kg. No differences were noted between the various BSA formulas using both weight and height for the calculation of BSA. The Bland–Altman analysis showed a proportional error between W PRED and BSA PRED up to the average daily dose of 60 mg, with a mean bias of 0.86 (95% limits of agreement = 0.68 to 1.05). Ten out of the 33 patients (30%) were given a lower than recommended BSA PRED dose by more than 5 mg/day. In conclusion, the dosage of prednisone at 2 mg/kg per day versus 60 mg/m² per day is not equivalent for patients with weights <30 kg and/or dose <60 mg/day.