Amelioration of cisplatin-induced neurodegenerative changes in rats and restoration of mitochondrial biogenesis by 6-bromoindirubin-3'-oxime: The implication of the GSK-3ß/PGC1-α axis.

BACKGROUND: The cognitive deficits observed after treatment with chemotherapeutic drugs are obvious clinical problems. For treating chemotherapy-induced cognitive deficits (CICD), the treatment modalities must target its underlying mechanisms. Specifically, cisplatin may activate glycogen synthase kinase-3ß (GSK-3ß), thereby enhancing neuronal apoptosis. 6-bromoindirubin-3'-oxime (6BIO) was not investigated previously in a model of CICD. Therefore, this investigation aimed to address the impacts of GSK3 inhibition on regulating cell signaling, which contributes to neurodegeneration and cognitive impairment. METHODS: Thirty adult male Wistar rats were randomly allocated into control groups, while two experimental groups were exposed to repeated cisplatin injections (2 mg/kg intraperitoneally (ip), twice weekly, nine injections), termed chemobrain groups. The rats in the two experimental groups were equally divided into the chemobrain group (untreated) and the chemobrain-6BIO group (treated with 6BIO at a dose of 8.5 µg/kg ip every two days, started after the last dose of cisplatin and continued for two weeks). RESULTS: Repeated exposure to cisplatin led to a marked decline in cognitive functions. GSK3 inhibition exerted neuroprotection by decreasing the expression of p-tau and amyloid ß, thereby improving cognition. 6BIO, the GSK-3ß inhibitor, restored mitochondrial biogenesis by augmenting the protein levels of PGC1-α and increasing the number of mitochondria in the cerebral cortex and hippocampus. CONCLUSION: 6BIO provided neuroprotection and exhibited anti-apoptotic and anti-oxidative effects in a rat model of chemobrain.

Associations of measured resting energy expenditure with predictive equations, NUTRIC score, and patient outcomes.

BACKGROUND: Indirect calorimetry is the reference method for measuring resting energy expenditure (REE), but the necessary equipment and technical expertise are not always available. Meanwhile, the NUTrition Risk in the Critically ill (NUTRIC) scale is designed to identify patients who would benefit from nutrition therapy, but no data are available regarding the association of NUTRIC scores with REE. Several predictive formulas are available as alternatives to indirect calorimetry for calculation of energy requirements, but they have not been compared in a homogeneous group of critically ill patients. The purpose of the study is to examine the correlations between energy expenditure and NUTRIC scores or patient outcomes, and to compare measured REE with estimations of energy expenditure. METHODS: In this observational, prospective study, indirect calorimetry was performed on 50 mechanically ventilated patients. Energy expenditure was also estimated with the bodyweight-based, Faisy-Fagon, and Penn-State PSUm equations. RESULTS: REE was higher in patients who survived treatment than in those who died, and was positively correlated with length of stay and duration of ventilation. NUTRIC scores did not correlate with REE. The Faisy-Fagon equation overestimated expenditure, whereas PSUm was unbiased and accurate. Calculations based on 25 kcal/kg bodyweight/day overestimated expenditure, whereas 23 kcal/kg/day produced unbiased estimates with greater accuracy than PSUm. CONCLUSION: REE was positively associated with patient outcomes. Energy expenditure was accurately predicted by calculations of 23 kcal/kg bodyweight/day.

Resveratrol suppresses cholestasis-induced liver injury and fibrosis in rats associated with the inhibition of TGFß1-Smad3-miR21 axis and profibrogenic and hepatic injury biomarkers.

Cholestasis caused by slowing or blockage of bile flow is a serious liver disease that can lead to liver fibrosis and cirrhosis. The link between transforming growth factor beta 1 (TGFß1), Smad family member 3 (Smad3), and microRNA 21 (miR21) in bile duct ligation (BDL)-induced liver fibrosis in the presence and absence of the anti-inflammatory and antioxidant compound, resveratrol (RSV), has not been previously studied. Therefore, we tested whether RSV can protect against BDL-induced liver fibrosis associated with the inhibition of the TGFß1-Smad3-miR21 axis and profibrogenic and hepatic injury biomarkers. The model group of rats had their bile duct ligated (BDL) for 3 weeks before being killed, whereas, the BDL-treated rats were separated into three groups that received 10, 20, and 30 mg/kg RSV daily until the end of the experiment. Using light microscopy and ultrasound examinations, we documented in the BDL group, the development of hepatic injury and fibrosis as demonstrated by hepatocytes necrosis, bile duct hyperplasia, collagen deposition, enlarged liver with increased echogenicity, irregular nodular border and dilated common bile duct, which were more effectively inhibited by the highest used RSV dosage. In addition, RSV significantly (p ≤ 0.0027) inhibited BDL-induced hepatic TGFß1, Smad3, miR21, the profibrogenic biomarker tissue inhibitor of metalloproteinases-1 (TIMP-1), malondialdehyde (MDA), interleukin-17a (IL-17a), and blood levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), and bilirubin. These findings show that RSV at 30 mg/kg substantially protects against BDL-induced liver injuries, which is associated with the inhibition of TGFß1-Smad3-miR21 axis, and biomarkers of profibrogenesis, oxidative stress, and inflammation.

Omega-3 attenuates high fat diet-induced kidney injury of female rats and renal programming of their offsprings.

Context: Maternal diet composition could influence fetal organogenesis. Objective: We investigated effects of high fat diet (HFD) intake alone or combined with omega 3 during pregnancy, lactation and early days of weaning on nephrogenesis of pups and maternal renal function and morphology. Material and methods: Mothers and their pups included in each group were supplied with the same diet composition. Rats were divided into group I, II and III supplied with chow of either 10 kcal%, 45 kcal% or 45 kcal% from fat together with omega-3 respectively. Results: Group II showed increased serum urea and creatinine, renal TNF-α, IL1ß. Structural injury was observed in mothers and their pups as Bowman's capsule and tubular dilatation and increased expression of PCNA that were decreased following omega-3 supplementation added to down regulation of Wnt4, Pax2 gene and podocin expression. Discussion and conclusion: Omega-3 supplementation improves lipid nephrotoxicity observed in mothers and their pups.

C2 pars/pedicle screws in management of craniocervical and upper cervical instability.

STUDY DESIGN: A retrospective study. PURPOSE: To evaluate the efficacy and the safety of craniocervical and upper cervical stabilization by using C2 pars/pedicle screw fixations. OVERVIEW OF LITERATURE: The management of craniocervical and upper cervical instability has progressed over the past two decades due to good achievements in the instrumentation and the increased awareness on spinal anatomy and biomechanics. However, there is insufficient studies or solid conclusions on this topic, thus, we tried to investigate and present our findings. METHODS: Twenty-two patients were operated upon and were followed up from March 2008 to October 2010. One patient had craniocervical instability (post-surgical), 15 patients had atlantoaxial instability of different etiologies (trauma, tumors, inflammatory and degenerative) and 6 patients had hangman fractures. Patients' ages ranged from 18 to 52 years old. with 5 female patients and 17 male patients. RESULTS: Radiological follow ups performed immediately post-operation showed good screw positioning and complete reductions in nearly all the cases. All patients were followed up for more than one year. Sound fusions were observed among all patients. CONCLUSIONS: The use of pars/pedicle screws is a very effective, sound, safe and easy surgical modality for treating craniocervical, atlantoaxial and upper cervical instabilities. Increasing studies for the biomechanics of this important region and longer periods of follow-ups are necessary to document the usefulness of this modality when treating such patients.