Olive (Olea europaea L.) leaf extract attenuates early diabetic neuropathic pain through prevention of high glucose-induced apoptosis: in vitro and in vivo studies

Aim of study

Since the leaves of olive have been recommended in the literature as a remedy for the treatment of diabetes and they also contain antioxidant agents, we decided to investigate the possible effects of olive leaf extract (OLE) on in vitro and in vivo models of diabetic pain neuropathy.

Materials and methods

The high glucose-induced cell damage in naive and NGF-treated Pheochromocytoma (PC12) cells and streptozotocin-induced diabetic rats were used. Tail-flick test was used to access nociceptive threshold. Cell viability was determined by MTT assay. Biochemical markers of neural apoptosis were evaluated using immunoblotting.

Results

We found that elevation of glucose (4 times of normal) sequentially increases functional cell damage and caspase-3 activation in NGF-treated PC12 cells. Incubation of cells with OLE (200, 400 and 600 μg/ml) decreased cell damage. Furthermore, the diabetic rats developed neuropathic pain which was evident from decreased tail-flick latency (thermal hyperalgesia). Activated caspase 3 and Bax/Bcl2 ratio were significantly increased in spinal cord of diabetic animals. OLE treatment (300 and 500 mg/kg per day) ameliorated hyperalgesia, inhibited caspase 3 activation and decreased Bax/Bcl2 ratio. Furthermore, OLE exhibited potent DPPH free radical scavenging capacity.

Conclusion

The results suggest that olive leaf extract inhibits high glucose-induced neural damage and suppresses diabetes-induced thermal hyperalgesia. The mechanisms of these effects may be due, at least in part, to reduce neuronal apoptosis and suggest therapeutic potential of olive leaf extract in attenuation of diabetic neuropathic pain.     

Autoimmune thyroid disease is associated with a diagnosis of secondary Sjögren's syndrome in familial systemic lupus

BACKGROUND: Autoimmune thyroid disease is common in systemic lupus erythematosus (SLE). About 20% of patients with SLE have secondary Sj?gren's syndrome. METHODS: Families with more than one patient with SLE were identified. All patients met the revised classification criteria, although SLE-unaffected relatives were confirmed not to satisfy these criteria. Diagnosis of autoimmune thyroid disease and Sj?gren's syndrome was made on the basis of a review of medical records, interview and questionnaire administered to patients with SLE, and by a questionnaire administered to SLE-unaffected subjects. RESULTS: Of a total of 1138 patients with SLE, 169 had a diagnosis of Sj?gren's syndrome. Of these 50 (29.6%) patients also had autoimmune thyroid disease. Of the 939 patients with SLE with no diagnosis of Sj?gren's syndrome, 119 (12.7%) had autoimmune thyroid disease (chi2 = 20.1, p = 0.000009). There was no association of a diagnosis of hypertension with secondary Sj?gren's syndrome (42% vss 47%). Among 2291 SLE-unaffected relatives, 44 had diagnosed primary Sj?gren's syndrome and 16 (36.3%) of these also had autoimmune thyroid disease. 265 of 2247 (11.8%) subjects had autoimmune thyroid disease but no Sj?gren's syndrome (chi2 = 24.2, p<0.001). CONCLUSIONS: Autoimmune thyroid disease is found in excess among patients with SLE with a diagnosis of secondary Sj?gren's syndrome, as well as among their SLE-unaffected relatives with a diagnosis of primary Sj?gren's syndrome.     

A large population-based study on the prevalence of electrocardiographic abnormalities: A result of Mashhad stroke and heart atherosclerotic disorder cohort study

Background

Twelve-lead electrocardiogram (ECG) is a common and inexpensive tool for the diagnostic workup of patients with suspected cardiovascular disease, both in clinical and epidemiological settings. The present study was designed to evaluate ECG abnormalities in Mashhad population.

Methods

ECGs were taken as part of MASHAD cohort study (phase1) and were coded according to the Minnesota coding criteria. Data were analyzed using SPSS.

Results

Total 9035 ECGs were available for final analysis including 3615 (40.0%) male and 5420 (60.0%) female. Among ECG abnormalities precordial Q wave, major T-wave abnormalities, inferior Q wave, sinus bradycardia, and left axis deviation were the most prevalent abnormalities. The frequency of precordial and inferior Q wave, inferior QS pattern, major and minor ST abnormalities, major and minor T abnormalities, Wolff-Parkinson-White and Brugada pattern, sinus bradycardia, sinus tachycardia, left axis deviation, ST elevation, and tall T wave were significantly different between two genders. Moreover, the frequency of Q wave in precordial and aVL leads, QS pattern in precordial and inferior leads, major and minor T-wave abnormalities, Wolff-Parkinson-White, atrial fibrillation, sinus bradycardia, left axis deviation, and ST elevation were significantly different in different age groups. A comparison of the heart rate, P-wave duration, and QRS duration between men and women indicated that there was a significant difference.

Conclusions

Our finding indicated that the prevalence ECG abnormalities are different between men and women and also it varied in different age groups.     

QSAR study of Phenoxypyrimidine Derivatives as Potent Inhibitors of p38 Kinase using different chemometric tools

Selective inhibition of the CSBP/p38 mitogen-activated protein kinase pathway may be an attractive target for the development of therapeutic agents to treat chronic inflammatory disease. A series of Phenoxypyrimidine Derivatives as Potent Inhibitors of p38 Kinase was subjected to quantitative structure-activity relationship (QSAR) analysis to find the structural requirements for ligand binding. A collection of chemometrics methods including multiple linear regression (MLR), factor analysis-based multiple linear regression (FA-MLR), principal component regression and partial least squared combined with genetic algorithm for variable selection (GA-PLS) were employed to make connections between structural parameters and enzyme inhibition. The results revealed the significant roles of steric effect, hydrogen bonding and electronic properties on the p38 inhibitory activity of the studied molecules. The most significant QSAR model, obtained by GA-PLS, could explain and predict 98% and 87% of variances in the pIC(50) data, respectively.     

Rotational dislocation of the thoracolumbar spine. Case report and review of the literature

The authors report a rare case of rotational dislocation of the thoracolumbar spine in a 12-year-old girl with neurofibromatosis Type 1. The patient had progressive spinal kyphoscoliosis with acute-onset paraplegia. She was treated with corrective traction preoperatively, followed by spinal decompression and circumferential spinal fusion without instrumentation. She had complete neurological recovery after a solid fusion of her spine.     

Effect of the duration of immunomodulatory therapy on the clinical features of recurrent episodes in Vogt–Koyanagi–Harada disease

Purpose: To evaluate the duration of immunomodulatory therapy (corticosteroids, immunosuppressive drugs) with regard to the rate of relapses and clinical features (exudative retinal detachment or anterior uveitis) in inflammatory episodes of Vogt–Koyanagi–Harada disease. Methods: Data of all 42 patients diagnosed with acute uveitis associated with VKH disease during the period of January 2005 to December 2008 at the Pitié‐Salpêtrière Hospital or at the Lariboisière Hospital in Paris, France were extracted by chart review. Results: There were 31 patients (73.8%) with episodes of recurrence and were included in the study. At the first recurrence, 81% (13 patients) of exudative retinal detachments (ERD) were associated with an initial immunomodulatory treatment conducted ≤6 months (3.76 months ± 2.67). Conversely, an initial treatment duration of >6 months was associated with anterior uveitis signs for 66% of patients (eight patients) with anterior first recurrence (p = 0.0061). On second episode of recurrence, 75% of patients (three patients) who developed exudative retinal detachment had been managed by immunomodulatory therapy for ≤6 months with the total duration of immunomodulatory treatment ≤6 months during previous inflammatory episodes. Conversely, all 16 patients who presented anterior uveitis with additional manifestations (optic disc oedema, macular oedema, vitritis and/or ‘Sunset glow’ fundus) have been treated for more than 6 months or treated during the initial occurrence lasting more than 9 months (p = 0.0035). Conclusions: The duration of systemic corticosteroids (and/or immunosuppressive drug therapy) for ≤6 months at first and second recurrence was associated with features of further exudative retinal detachment instead of anterior uveitis in VKH disease.