Phosphorylation of rat aquaporin‐4 at Ser111 is not required for channel gating

Aquaporin 4 (AQP4) is the predominant water channel in the mammalian brain and is mainly expressed in the perivascular glial endfeet at the brain‐blood interface. AQP4 has been described as an important entry and exit site for water during formation of brain edema and regulation of AQP4 is therefore of therapeutic interest. Phosphorylation of some aquaporins has been proposed to regulate their water permeability via gating of the channel itself. Protein kinase (PK)‐dependent phosphorylation of Ser¹¹¹ has been reported to increase the water permeability of AQP4 expressed in an astrocytic cell line. This possibility was, however, questioned based on the crystal structure of the human AQP4. Our study aimed to resolve if Ser¹¹¹ was indeed a site involved in phosphorylation‐mediated gating of AQP4. The water permeability of AQP4‐expressing Xenopus oocytes was not altered by a range of activators and inhibitors of PKG and PKA. Mutation of Ser¹¹¹ to alanine or aspartate (to prevent or mimic phosphorylation) did not change the water permeability of AQP4. PKG activation had no effect on the water permeability of AQP4 in primary cultures of rat astrocytes. Molecular dynamics simulations of a phosphorylation of AQP4.Ser¹¹¹ recorded no phosphorylation‐induced change in water permeability. A phospho‐specific antibody, exclusively recognizing AQP4 when phosphorylated on Ser¹¹¹, failed to detect phosphorylation in cell lysate of rat brain stimulated by conditions proposed to induce phosphorylation of this residue. Thus, our data indicate a lack of phosphorylation of Ser¹¹¹ and of phosphorylation‐dependent gating of AQP4.     

Pharmacologic management of neuropathic pain: evidence-based recommendations

Patients with neuropathic pain (NP) are challenging to manage and evidence-based clinical recommendations for pharmacologic management are needed. Systematic literature reviews, randomized clinical trials, and existing guidelines were evaluated at a consensus meeting. Medications were considered for recommendation if their efficacy was supported by at least one methodologically-sound, randomized clinical trial (RCT) demonstrating superiority to placebo or a relevant comparison treatment. Recommendations were based on the amount and consistency of evidence, degree of efficacy, safety, and clinical experience of the authors. Available RCTs typically evaluated chronic NP of moderate to severe intensity. Recommended first-line treatments include certain antidepressants (i.e., tricyclic antidepressants and dual reuptake inhibitors of both serotonin and norepinephrine), calcium channel alpha2-delta ligands (i.e., gabapentin and pregabalin), and topical lidocaine. Opioid analgesics and tramadol are recommended as generally second-line treatments that can be considered for first-line use in select clinical circumstances. Other medications that would generally be used as third-line treatments but that could also be used as second-line treatments in some circumstances include certain antiepileptic and antidepressant medications, mexiletine, N-methyl-D-aspartate receptor antagonists, and topical capsaicin. Medication selection should be individualized, considering side effects, potential beneficial or deleterious effects on comorbidities, and whether prompt onset of pain relief is necessary. To date, no medications have demonstrated efficacy in lumbosacral radiculopathy, which is probably the most common type of NP. Long-term studies, head-to-head comparisons between medications, studies involving combinations of medications, and RCTs examining treatment of central NP are lacking and should be a priority for future research.     

Aetiological risk factors are associated with distinct imaging findings in patients with chronic pancreatitis: A study of 959 cases from the Scandinavian Baltic Pancreatic Club (SBPC) imaging database

ObjectivesThe relation between aetiology and structural changes of the pancreas in patients with chronic pancreatitis (CP) is not fully understood. Earlier studies are limited by focusing on selected factors in studies of limited sample size. We aimed to use a large dataset to explore associations between aetiology and pancreatic morphology in CP.MethodsSubjects with definite or probable CP according to the M-ANNHEIM diagnostic criteria were included in this multicentre cross-sectional observational study and assessed using a standardized and validated CP imaging system. We performed multivariate logistic regression to analyse if aetiological factors adjusted for covariates were independently associated with morphological pancreatic features.ResultsWe included 959 patients (66% males). Mean (SD) age was 55 (14) years. Pancreatic structural changes were found in 94% of the subjects: 67% had calcifications, 59% main pancreatic duct dilatation, 33% pseudo-cysts and 22% pancreatic atrophy. Alcohol abuse was independently associated with pancreatic calcifications (odds ratio (OR, [95% CI]); 1.61, [1.09, 2.37]) and focal acute pancreatitis (OR; 2.13, [1.27, 3.56]), whereas smoking was independently associated with more severe calcifications (OR; 2.09, [1.34, 3.27]) and involvement of the whole gland (OR; 2.29, [1.61, 3.28]). Disease duration was positively associated with calcifications (OR; (per year) 1.05 [1.02, 1.08]) and pancreatic atrophy (OR; 1.05 [1.02, 1.08]) and negatively associated with focal acute pancreatitis (OR 0.91, [0.87, 0.95] and pseudo cysts (OR; 0.96, [0.93, 0.98]).ConclusionIn this large-scale study, etiological risk factors and disease duration in CP were independently associated with specific structural pancreatic imaging changes.     

消栓通脉颗粒逆转Th1／Th2亚群失衡治疗大鼠深静脉血栓

目的探讨Th1／Th2亚群失衡在大鼠深静脉血栓形成（DVT）中的作用及中药复方消栓通脉颗粒逆转Th1／Th2亚群失衡治疗DVT的作用机制。方法80只DVT大鼠随机分为消栓通脉颗粒组、DVT组、假手术组、正常组,分离大鼠脾脏单个核细胞,流式细胞术检测各组大鼠Thl亚群（CD4＋TNF—α）、Th2亚群（CD4＋IL-4＋）比例,ELISA法检测大鼠外周血TNF—α、IL-4水平。结果与正常组及假手术组比较,DVT大鼠脾脏Th1亚群比例显著升高（P=0．022）,Th2亚群比例显著降低（P=0．015）;血清TNF-α水平显著升高（P=0．005）;IL-4水平显著降低（P=0．012）。消栓通脉颗粒作用后,大鼠脾脏Thl亚群比例显著降低（P=0．008）,Th2亚群比例显著升高（P=0．011）,血清TNF-α水平降低（P=0．036）,IL-4水平升高（P=0．018）。结论Th1／Th2亚群失衡参与了大鼠DVT发病过程,消栓通脉颗粒诱导T细胞向Th2亚群偏移,抑制炎性因子表达进而减轻炎症反应,保护血管内皮细胞,促进血栓再通。     

Internal transcardiac pericardiocentesis for acute tamponade

If the catheter is still in the pericardium when tamponade is recognized during catheterization or electrophysiologic procedures, it can be used for definitive aspiration and relief of tamponade. This is physiologically beneficial to the patient, and psychologically beneficial to both patient and medical staff.     

High vitamin A content in some small indigenous fish species in Bangladesh: perspectives for food-based strategies to reduce vitamin A deficiency

Recognising the importance of fish in the Bangladeshi diet, the objective of the present study was to screen commonly consumed fish species for vitamin A content to evaluate the potential of fish as a vitamin A source in food-based strategies to combat vitamin A deficiency. Samples of 26 commonly consumed fish species and one crustacean were collected in Kishoreganj and Mymensingh, Bangladesh. To obtain edible parts, the fish were cleaned by Bangladeshi women according to traditional practices. Distribution of vitamin A in parts of the fish and the effect of the cleaning practices on the vitamin A content in#10; edible parts were assessed. The content of vitamin A compounds was analysed by high-performance liquid chromatography. The vitamin A content in small fish ranged from 2680 retinol equivalents (RE)/100 g raw edible parts in mola (Amblypharyngodon mola) to 20 RE/100 g raw edible parts in chata (Colisa lalia; an alternative scientific name is Colisa lalius). The vitamin A content in cultured species, silver carp (Hypophthalmichthys molitrix), rui (Labeo rohita), mrigal (Cirrhinus mrigala) and tilapia (Oreochromis niloticus) was low, <30 RE/100 g raw edible parts. In mola, 90% of the vitamin A was found in the eyes and viscera. The vitamin A content in the screened fish species was highly variable, by more than a factor of 100. The existence of commonly consumed fish in Bangladesh belonging to the categories of very high and high vitamin A content offers a great unexploited potential for food-based strategies to improve the vitamin A intake by promoting the production and consumption of these species.