Carbocisteine as a Modulator of Nrf2/HO-1 and NFκB Interplay in Rats: New Inspiration for the Revival of an Old Drug for Treating Ulcerative Colitis.

Ulcerative colitis (UC), an inflammatory bowel disease, is a chronic condition of a multifaceted pathophysiology. The incidence of UC is increasing internationally. The current therapies for UC lack relative effectiveness and are associated with adverse effects. Therefore, novel therapeutic options should be developed. It has been well documented that modulating the Nrf2/NFκB is a promising therapeutic target in inflammation. Carbocisteine is a mucoregulatory medication and its efficacy in COPD was found to be more closely related to its antioxidant and anti-inflammatory properties. Carbocisteine has not yet been examined for the management of UC. Hence, our approach was to investigate the potential coloprotective role of carbocisteine in acetic acid-induced colitis in rats. Our results revealed that carbocisteine improved colon histology and macroscopic features and subdued the disease activity as well. Additionally, carbocisteine attenuated colon shortening and augmented colon antioxidant defense mechanisms via upregulating catalase and HO-1 enzymes. The myeloperoxidase activity was suppressed indicating inhibition of the neutrophil infiltration and activation. Consistent with these findings, carbocisteine boosted Nrf2 expression along with NFκB inactivation. Consequently, carbocisteine downregulated the proinflammatory cytokines IL-6 and TNF-α and upregulated the anti-inflammatory cytokine IL-10. Concomitant to these protective roles, carbocisteine displayed anti-apoptotic properties as revealed by the reduction in the Bax: BCL-2 ratio. In conclusion, carbocisteine inhibited oxidative stress, inflammatory response, and apoptosis in acetic acid-induced UC by modulating the Nrf2/HO-1 and NFκB interplay in rats. Therefore, the current study provides a potential basis for repurposing a safe and a commonly used mucoregulator for the treatment of UC.

ß-lactamases (bla TEM, bla SHV, bla CTXM-1, bla VEB, bla OXA-1 ) and class C ß-lactamases gene frequency in Pseudomonas aeruginosa isolated from various clinical specimens in Khartoum State, Sudan: a cross sectional study.

Background:Pseudomonas aeruginosa is a pathogenic bacterium, causing nosocomial infections with  intrinsic and acquired resistance mechanisms to a large group of antibiotics, including ß-lactams. This study aimed to determine the susceptibility pattern to selected antibiotics and to index the first reported ß-lactamases genes frequency in Ps. aeruginosa in Khartoum State, Sudan. Methods: 121 Ps. aeruginosa clinical isolates from various clinical specimens were used in this cross sectional study conducted in Khartoum State. Eighty isolates were confirmed as Ps.aeruginosa through conventional identification methods and species specific primers. The susceptibility pattern of the confirmed isolates to selected antibiotics was done following the Kirby Bauer disk diffusion method. Multiplex PCR was used for detection of seven ß-lactamase genes ( blaTEM, blaSHV, blaCTXM-1, blaVEB, blaOXA-1, blaAmpC and blaDHA). Results: Of the 80 confirmed Ps. aeruginosa isolates, 8 (10%) were resistant to Imipenem while all isolates were resistant to Amoxicillin and Amoxyclav (100%). A total of 43 (54%) Ps. aeruginosa isolates were positive for blaTEM, blaSHV, blaCTXM-1, blaVEB and blaOXA-1 genes, while 27 (34%) were positive for class C ß- Lactamases, and 20 (25%) were positive for both classes. Frequency of beta-lactamases genes was as follows: blaTEM, 19 (44.2%); blaSHV, 16 (37.2%); bla CTX-M1, 10 (23.3%); blaVEB, 14 (32.6%); blaOXA-1, 7 (16.3%). blaAmpC 22 (81.5%) and bla DHA 8 (29.6%).  In total, 3 (11.1%) isolates were positive for both bla AmpC and blaDHA genes. Conclusion:Ps. aeruginosa isolates showed a high rate of ß- lactamases production, with co-resistance to other antibiotic classes. The lowest resistance rate of Ps. aeruginosa was to Imipenem followed by Gentamicin and Ciprofloxacin. No statistically significant relationship between production of ß-lactamases in Ps. aeruginosa and resistance to third generation cephalosporins was found.

Serum sclerostin level and its relation to subclinical atherosclerosis in subjects with type 2 diabetes.

BACKGROUND: Sclerostin, a Wnt-signalling inhibitor, is an established negative regulator of bone formation. However, data regarding its potential importance in vascular disease are less clear. Common carotid artery media thickness (CIMT) assessment and plaque identification using ultrasound imaging are well-recognized tools for identifying and monitoring atherosclerosis. The aim of the present study is to examine the relationship between serum sclerostin and subclinical atherosclerosis (as evidenced by CIMT). METHODS: This cross-sectional study included 50 subjects with T2DM and 20 subjects as a control group. Multivariable linear regression models were used to assess the association of sclerostin with subclinical atherosclerosis. RESULTS: Serum sclerostin levels in T2DM patients were significantly higher compared to the control group (167.16 ±â€¯63.60 versus 85.98 ±â€¯23.74 pg/ml, P < 0.0001). A concentration of ≥162.5 pg/ml showed a sensitivity of 90% and a specificity of 86.67% to detect an increased risk of subclinical atherosclerosis. Univariate analysis revealed a significant positive correlation between serum sclerostin and CIMT (r = 0.635, P < 0.001). Sclerostin concentrations remained independently associated with CIMT (ß = 63.188 [6.919-119.456], P = 0.017) after adjusting for age and gender. CONCLUSION: Our data suggest a positive correlation between serum sclerostin level and subclinical atherosclerosis in subjects with type 2 diabetes mellitus.