Impact of Aortic Cross-Clamping Time on Peripheral Nerves: Experimental Model

Purpose: The present study investigated the correlation between extend aortic cross-clamping time and peripheral nerve injury on rats.Methods: 24 male, Sprague Dawley rats were divided into 3 groups; (a) control group: abdomen was directly closed after reached aorta, and followed by 72 hours, (b) short-term ischaemia-reperfusion group: peripheral nerve ischemia was induced in rats by supraceliac aortic occlusion for 20 min followed by 72 h of reperfusion, (c) long-term ischaemia-reperfusion group: peripheral nerve ischemia was induced for 30 min followed by 72 h of reperfusion. Preoperative and postoperative, electromyography (EMG) recordings were done. End of 72 h, the sciatic nerves were harvested from each animal for histopathological and biochemical analysis.Results: The mean compound muscle action potential (CMAP) amplitude of long-term ischaemia-reperfusion group was statically significant reduced when compared to the control group (p <0.01). However, the mean distal latency value of long-term ischaemia-reperfusion group was statically significant increased (p <0.01). On the other hand, there were statically significant differences between the results of malondialdehyde, edema and ischemia fiber degeneration grades on control and long-term ischaemia-reperfusion group (p <0.001).Conclusion: This study demonstrated that the extending cross clamping time directly harms the peripheral nerve of rats.     

Lifestyle Management for Enhancing Outcomes after Bariatric Surgery

Bariatric surgery has been safe and effective for treatment of severe obesity and comorbidities like type 2 diabetes mellitus (T2D). Nonetheless, weight loss and health outcomes vary considerably across individuals. Although the factors associated with outcomes are not fully understood, postoperative weight loss following any type of bariatric surgery is largely dependent on the extent to which patients can make and sustain changes in eating and activity. Therefore, lifestyle management including diet, exercise, and behavior modification is critical to helping patients achieve long-term weight loss. Pharmacotherapy and reoperation may also play a role after bariatric surgery. In this article, we highlight recent research findings in all of these areas to provide suggestions for how to enhance outcomes following bariatric surgery. Research on the mechanisms for weight loss and improvements in T2D following the different surgical procedures is needed to support the development of more personalized approaches to the multidisciplinary management of severe obesity.     

Identification of neuronal substrates implicates Pak5 in synaptic vesicle trafficking

Synaptic transmission is mediated by a complex set of molecular events that must be coordinated in time and space. While many proteins that function at the synapse have been identified, the signaling pathways regulating these molecules are poorly understood. Pak5 (p21-activated kinase 5) is a brain-specific isoform of the group II Pak kinases whose substrates and roles within the central nervous system are largely unknown. To gain insight into the physiological roles of Pak5, we engineered a Pak5 mutant to selectively radiolabel its substrates in murine brain extract. Using this approach, we identified two novel Pak5 substrates, Pacsin1 and Synaptojanin1, proteins that directly interact with one another to regulate synaptic vesicle endocytosis and recycling. Pacsin1 and Synaptojanin1 were phosphorylated by Pak5 and the other group II Paks in vitro, and Pak5 phosphorylation promoted Pacsin1-Synaptojanin1 binding both in vitro and in vivo. These results implicate Pak5 in Pacsin1- and Synaptojanin1-mediated synaptic vesicle trafficking and may partially account for the cognitive and behavioral deficits observed in group II Pak-deficient mice.     

Type II p21-activated kinases (PAKs) are regulated by an autoinhibitory pseudosubstrate

The type II p21-activated kinases (PAKs) are key effectors of RHO-family GTPases involved in cell motility, survival, and proliferation. Using a structure-guided approach, we discovered that type II PAKs are regulated by an N-terminal autoinhibitory pseudosubstrate motif centered on a critical proline residue, and that this regulation occurs independently of activation loop phosphorylation. We determined six X-ray crystal structures of either full-length PAK4 or its catalytic domain, that demonstrate the molecular basis for pseudosubstrate binding to the active state with phosphorylated activation loop. We show that full-length PAK4 is constitutively autoinhibited, but mutation of the pseudosubstrate releases this inhibition and causes increased phosphorylation of the apoptotic regulation protein Bcl-2/Bcl-X_L antagonist causing cell death and cellular morphological changes. We also find that PAK6 is regulated by the pseudosubstrate region, indicating a common type II PAK autoregulatory mechanism. Finally, we find Src SH3, but not β-PIX SH3, can activate PAK4. We provide a unique understanding for type II PAK regulation.     

Polyarteritis nodosa and Henoch–Schönlein purpura nephritis in a child with familial Mediterranean fever: a case report

Familial Mediterranean fever is an autosomal recessive disease characterized by recurrent self-limited attacks of fever accompanied by peritonitis, pleuritis, and arthritis. Approximately 5% of individuals with familial Mediterranean fever have been reported to have Henoch–Schonlein purpura and about 1% to have polyarteritis nodosa. A 7-year-old girl presenting with complaints of purpuric rash, abdominal pain, arthritis, hematuria, and proteinuria and having IgA depositions on renal biopsy was diagnosed as Henoch–Schönlein nephritis. She had a history of recurrent fever, abdominal and joint pain and M694 V compound homozygote mutation. Colchicine treatment was started for the diagnosis of FMF. When constitutional symptoms such as myalgia, weight loss, fatigue, fever, and hypertension were added to the clinical picture, the diagnosis of polyarteritis nodosa HSP was thought and confirmed by the demonstration of microaneurisms on renal arteries. There was no response to corticosteroid and cyclophosphamide treatments; however, the symptoms were rapidly and dramatically reduced after the administration of intravenous immunoglobulin. In conclusion, polyarteritis nodosa and Henoch–Schonlein purpura can be seen together with familial Mediterranean fever. It is also suggested that IVIG might be an important adjunct therapy in selected patients with polyarteritis nodosa, especially in the lack of response to steroids and immunsuppressive drugs.     

Low frequency of filaggrin null mutations in Croatia and their relation with allergic diseases

Filaggrin gene (FLG) null mutations are considered associated with atopic dermatitis. This study was conducted to determine the prevalence of FLG null mutations R501X, 2282del4, R2447X and S3247X in the Croatian population and their role in the occurrence of allergic diseases including atopic dermatitis, allergic rhinitis, asthma and allergic contact dermatitis (ACD). Study enrolled 440 freshmen with defined allergic diseases by means of both present symptoms in International Study of Asthma and Allergies in Childhood questionnaire (relevant respiratory and/or skin symptoms) and markers of allergic sensitization (positive skin prick and/or patch test). FLG null mutations were successfully genotyped in 423 students of which 11 (2.6%) were carriers of FLG null mutation: 1/423 (0.2%) was heterozygous for R501X and 10/423 (2.4%) were heterozygous for 2282del4. No carriers of R2447X and S3247X mutations were identified. In wild‐type FLG carriers (412 subjects), atopic dermatitis was present in 45 (11%), allergic rhinitis in 70 (17%) and allergic asthma in 29 (7%) students. Twenty‐five of 393 (7%) patch‐tested wild‐type FLG carriers had ACD. Among 11 FLG null mutation carriers, four had one or more allergic diseases, and five had reported skin symptoms without defined allergic sensitization (positive skin prick test and/or patch test). FLG null mutations were not confirmed as a predictor of analysed allergic diseases, but were confirmed as an independent predictor of skin symptoms (OR 17.19, 95% CI 3.41–86.6, P < 0.001). Our results in general indicate a low frequency of FLG null mutations in the studied Croatian population supporting a theory of a latitude‐dependent distribution of FGL null mutations in Europe, with a decreasing north–south gradient of R501X and 2282del4 mutation frequency. The relation between FLG null mutations and skin disorders was confirmed.     

Multiple co-infections of rodents with hantaviruses, Leptospira, and Babesia in Croatia

Hantaviruses, Leptospira spp., and Babesia spp. are rodent-borne pathogens present worldwide. We studied multiple co-infections of small rodents in Croatia with all three pathogens. Twenty-eight Apodemus flavicollis and 16 Myodes glareolus were tested for the presence of hantavirus RNA by real-time RT-PCR, Leptospira strains by renoculture method and Babesia DNA by PCR. Anti-hantavirus antibodies and anti-Leptospira antibodies were detected by serological methods. Very high infection rates with each pathogen were found in A. flavicollis: 20 of 28 rodents (71%) were infected with Dobrava virus, 13 rodents (46%) were infected with Leptospira, and 5 rodents (18%) were infected with Babesia. Multiple co-infections with all three pathogens were found in 3 of 28 (11%) A. flavicollis animals, suggesting that the same rodent host can be infected with several pathogens at the same time. Dual infections with both hantaviruses and Leptospira were found in 7 of 44 rodents (16%), with hantaviruses and Babesia in 2 rodents (5%), and double infection with both Leptospira and Babesia were found in 1 rodent (2%). Since hantaviruses, Leptospira, and Babesia have similar geographical distributions, it is to be expected that in other parts of the world multiple co-infections, representing a serious threat to public health, can be found.     

Digoxin intoxication: An old enemy in modern era

Objectives Although development of new treatment modalities limited digoxin usage, digoxin intoxication is still an important issue which could be easily overlooked. In this report we analyzed a case series definitively diagnosed as digoxin intoxication in the modern era. Methods We analyzed 71 patients hospitalized with digoxin intoxication confirmed by history, complaints, clinical and electrocardiograph (ECG) findings, and serum digoxin levels > 2.0 ng/mL, during a five year period. The demographic and clinical data, indications for digoxin use, digoxin dosage, concurrent medications, laboratory data, hospital monitoring, and ECG findings were obtained from all patients. Results Thirty-eight of 71 patients (53.5%) had symptoms of heart failure during admission or later. Sixty-four percent of patients were older than 75 years. The percentage of females was 67%. Atrial fibrillation, hypertension and gastrointestinal complaints were more frequent in the females (64% in females, 30% in males, P = 0.007; 81% in female, 52% in males, P = 0.01; 50% in female, 17.3% in males, P = 0.008, respectively). The mortality rate during the hospital course was 7%. Conclusion This report demonstrated the reduced mortality rates in patients with digoxin intoxication over the study period. Gastrointestinal complaints are the most common symptoms in this population.     

Tramadol and levobupivacaine wound infiltration at Cesarean delivery for postoperative analgesia

Purpose

The aim of the present study was to investigate whether levobupivacaine and tramadol wound infiltration decreases postoperative pain following Cesarean section and reduces the need for analgesics in the immediate post-delivery period.

Methods

Ninety patients (aged 18–40 years) scheduled for elective Cesarean section under general anesthesia were randomly allocated to one of the three groups: the placebo group (group P) received 20 mL local wound infiltration with 0.9 % saline solution; the levobupivacaine group (group L) received 20 mL local wound infiltration with levobupivacaine 0.25 %; and the tramadol group (group T) received 20 mL local wound infiltration with 1.5 mg/kg tramadol within 0.9 % saline solution. Following the closure of the uterine incision and the rectus fascia, 20 mL solution was infiltrated subcutaneously along the skin wound edges. The primary outcome was 24-h tramadol consumption. Secondary outcomes were recorded VAS scores, diclofenac requirement, fever, vomiting, and wound infection.

Results

At 15 min postoperatively, VAS values were lower in groups T and L than group P (P = 0.0001). The mean 24-h tramadol consumption was lowest in group T (P = 0.0001) and it was lower in the group L compared to group P (P = 0.007) (401.6, 483.3, and 557.5 mg for T, L, and P groups, respectively). There was no difference among groups regarding the need for supplemental analgesia (rescue diclofenac doses) (P > 0.05).

Conclusions

We conclude that wound infiltration with tramadol and levobupivacaine in patients having Cesarean section under general anesthesia may be a good choice for postoperative analgesia.