5-aminoimidazole-4-carboxamide-1-beta-4-ribofuranoside (AICAR) attenuates the expression of LPS- and Aβ peptide-induced inflammatory mediators in astroglia

Background  

Alzheimer's disease (AD) pathology shows characteristic 'plaques' rich in amyloid beta (Aβ) peptide deposits. Inflammatory process-related proteins such as pro-inflammatory cytokines have been detected in AD brain suggesting that an inflammatory immune reaction also plays a role in the pathogenesis of AD. Glial cells in culture respond to LPS and Aβ stimuli by upregulating the expression of cytokines TNF-α, IL-1β, and IL-6, and also the expression of proinflammatory genes iNOS and COX-2. We have earlier reported that LPS/Aβ stimulation-induced ceramide and ROS generation leads to iNOS expression and nitric oxide production in glial cells. The present study was undertaken to investigate the neuroprotective function of AICAR (a potent activator of AMP-activated protein kinase) in blocking the pro-oxidant/proinflammatory responses induced in primary glial cultures treated with LPS and Aβ peptide.     

Antitumor AHMA linked to DNA minor groove binding agents: synthesis and biological evaluation

DNA minor groove binder hybrid molecules, netropsin derivatives such as N-[2-(dimethylamino)ethyl]-1-methyl-4-aminopyrrolo-2-carboxamide (MePy) or its derivatives containing two units of N-methylpyrrolecarboxamide (diMePy) and bisbenzimidazole (Ho33258), were linked to the NH(2) function of AHMA or to the CH(2)OH group of AHMA-ethylcarbamate to form AHMA-N-netropsins (13-16) and AHMA-ethylcarbamate-O-netropsins (19-22), and AHMA-bisbenzimidazole (AHMA-Ho33258, 25), respectively. These conjugates' in vitro antitumor activity, inhibition of a variety of human tumor cell growth, revealed that AHMA-ethylcarbamate-O-netropsin derivatives were more cytotoxic than AHMA-N-netropsin compounds. In the same studies, all compounds bearing MePy were more potent than those compounds linked with diMePy. Moreover, AHMA-netropsin derivatives bearing a succinyl chain as the linking spacer were more potent than those compounds having a glutaryl bridge. Among these hybrid molecules, AHMA-ethylcarbamate-O-succinyl-MePy (19) was 2- to 6-fold more cytotoxic than the parent compound AHMA (5) in various cell lines, whereas compound 25 had very poor solubility and was inactive. Studies on the inhibitory effect against topoisomerase II (Topo II) and DNA interaction of these conjugates showed no correlation between the potency of DNA binding and inhibitory activity against Topo II.     

Mannose-binding lectin gene polymorphisms in a cohort study of ANCA-associated small vessel vasculitis

OBJECTIVE: To investigate whether single nucleotide polymorphisms (SNPs) within the mannose-binding lectin (MBL) gene are associated with small vessel vasculitis (SVV) and are a risk factor for intercurrent infection, as described previously in other autoimmune diseases. METHODS: Six SNPs in the MBL promoter and coding region were genotyped by sequence-specific polymerase chain reaction or restriction fragment length polymorphism assay in 170 white Caucasians with SVV and 372 ethnically matched controls in a case-control association study. Serum MBL levels were measured by ELISA. The genotype and protein concentrations were correlated to clinical details retrieved from hospital records. RESULTS: No differences in allelic and genotypic frequencies were detected between patients with SVV and control subjects. MBL deficiency did not increase the susceptibility to infection (P = 0.6, Fisher's exact test) or the duration of hospital stay. CONCLUSION: Our data suggest that MBL polymorphisms are not associated with SVV and do not influence the incidence of concomitant infections. These results raise doubts about the usefulness of MBL polymorphisms as a predictive marker for infection in SVV.     

Antihypercholesterolemic effect of Bacopa monniera linn. on high cholesterol diet induced hypercholesterolemia in rats

ObjectiveTo explore the effect of alcoholic extract of Bacopa monniera (AEBM) on high cholesterol diet-induced rats.MethodsThe shade-dried and coarsely powdered whole plant material (Bacopa monniera) was extracted with 90% ethanol, finally filtered and dried in vacuum pump. The experimental rats were divided into 4 groups: control (group-I), Rats fed with hypercholesterolemic diet (HCD) for 45 days [4% cholesterol (w/w) and 1% cholic acid], Rats fed with HCD for 45 days+AEBM (40mg/kg, body weight/day orally) for last 30 days (group-III) and AEBM alone (group-IV). Blood and tissues (Aorta) were removed to ice cold containers for various biochemical and histological analysis.ResultsAEBM treatment significantly decreased the levels of TC, TG, PL, LDL, VLDL, atherogenic index, LDL/HDL ratio, and TC/HDL ratio but significantly increased the level of HDL when compared to HCD induced rats. Activities on liver antioxidant status (SOD, CAT, GPx, GR, GST) were significantly raised with concomitant reduction in the level of LPO were obtained in AEBM treated rats when compared to HCD rats. Treatment with AEBM significantly lowered the activity of SGOT, LDH and CPK. Histopathology of aorta of cholesterol fed rat showed intimal thickening and foam cell deposition were noted.ConclusionsThese results suggests that AEBM extended protection against various biochemical changes and aortic pathology in hypercholesterolemic rats. Thus the plant may therefore be useful for therapeutic treatment of clinical conditions associated hypercholesterolemia.     

Hypocholesterolemic efficacy of royal jelly in healthy mild hypercholesterolemic adults

Context: Royal jelly (RJ) has been reported for its health promoting factors such as antioxidant, anti-inflammatory and lipid lowering activities.

Objective: The present randomized, placebo-controlled study examines the hypolipidemic beneficial effect of RJ through evaluating anthropometric measurements, lipid profile and various hormone levels in mildly hypercholesterolemic participants.

Materials and methods: Forty subjects with mild hypercholesterolemia (180–200?mg/dL) were randomly selected and divided into two groups as experimental or placebo, who requested to intake nine capsules (350?mg/capsule) of RJ or placebo/day, respectively, for three months with one month of follow-up without any supplementation.

Results: No significant changes were noted in any of the anthropometric parameters like body weight, waist and body fat. The serum total cholesterol (TC; 207.05–183.15?mg/dL) and low-density lipoprotein cholesterol (LDL-c; 126.44–120.31?mg/dL) levels were reduced significantly (p?p?Discussion and conclusion: Intervention with RJ for three months considerably lowered the TC and LDL-c levels through improving the levels of DHEA-S and thus alleviates the risk of cardiovascular disease (CVD).     

Nephroprotective potential of Bacopa monniera on hypercholesterolemia induced nephropathy via the NO signaling pathway

Context: Bacopa monniera L. (Scrophulariaceae) is used as a traditional medicine in India for various ailments such as epilepsy, mental disorders, and also as a cardio-tonic. However, its nephroprotective role is still unknown.

Objective: The present study assesses the modulatory impact of the alcoholic (ethanol) extract of Bacopa monniera (AEBM) on renal oxido-lipidemic stress in hypercholesterolemic rats.

Materials and methods: B. monniera (1?kg) was extracted with 90% ethanol, filtered, and dried (52?g). Group-I rats as control, Group-II rats fed with a hypercholesterolemic diet (HCD) for 45?d [4% cholesterol and 1% cholic acid], Group-III rats fed with HCD for 45?d?+?AEBM (40?mg/kg, body weight) for last 30?d, and Group-IV AEBM alone rats. Blood and kidney were removed to analyze lipid, antioxidant status, and histological analysis.

Result: The levels of total cholesterol (TC), triacylglycerol (TG), phospholipids (PLs), renal functional parameters (urea, creatinine, and uric acid), and lipid peroxidation (LPO) products were significantly attenuated (p?S-transferase (GST), and glutathione reductase (GR)) and non-enzymic antioxidant (GSH, Vit-C, and Vit-E) were significantly increased (p?p?Discussion and conclusion: From this study, we hypothesized that AEBM can act as renoprotective agent by attenuating the renal oxido-lipidemic stress via regulating NOS level and thereby protects the nephron in hypercholesterolemic rats.     

Are urological procedures in tetraplegic patients safely performed without anesthesia? a report of three cases

Background

Some tetraplegic patients may wish to undergo urological procedures without anaesthesia, but these patients can develop autonomic dysreflexia if cystoscopy and vesical lithotripsy are performed without anaesthesia.

Case presentation

We describe three tetraplegic patients, who developed autonomic dysreflexia when cystoscopy and laser lithotripsy were carried out without anesthesia. In two patients, who declined anaesthesia, blood pressure increased to more than 200/110 mmHg during cystoscopy. One of these patients developed severe bleeding from bladder mucosa and lithotripsy was abandoned. Laser lithotripsy was carried out under subarachnoid block a week later in this patient, and this patient did not develop autonomic dysreflexia. The third patient with C-3 tetraplegia had undergone correction of kyphoscoliotic deformity of spine with spinal rods and pedicular screws from the level of T-2 to S-2. Pulmonary function test revealed moderate to severe restricted curve. This patient developed vesical calculus and did not wish to have general anaesthesia because of possible need for respiratory support post-operatively. Subarachnoid block was not considered in view of previous spinal fixation. When cystoscopy and laser lithotripsy were carried out under sedation, blood pressure increased from 110/50 mmHg to 160/80 mmHg.

Conclusion

These cases show that tetraplegic patients are likely to develop autonomic dysreflexia during cystoscopy and vesical lithotripsy, performed without anaesthesia. Health professionals should educate spinal cord injury patients regarding risks of autonomic dysreflexia, when urological procedures are carried out without anaesthesia. If spinal cord injury patients are made aware of potentially life-threatening complications of autonomic dysreflexia, they are less likely to decline anaesthesia for urological procedures. Subrachnoid block or epidural meperidine blocks nociceptive impulses from urinary bladder and prevents occurrence of autonomic dysreflexia. If spinal cord injury patients with lesions above T-6 decline anaesthesia, nifedipine 10 mg should be given sublingually prior to cystoscopy to prevent increase in blood pressure due to autonomic dysreflexia.