Evaluation of Antihypertensive Effect of Aqueous Methanol Extract of Caralluma tuberculata N.E.Br in Sprauge Dawley Rats

Purpose: To evaluate the phytochemical profile and antihypertensive effect of Caralluma tuberculata N.E.Br (AMECT).Methods: The antihypertensive effect of the aqueous methanol extract of (AMECT) was evaluated in both normotensive and hypertensive rats. In normotensive rats, various doses (100, 300 and 500 mg/kg body weight, p.o.) were administered at 0, 1, 3 and 6 hr intervals. Anti-hypertensive activity of the crude extract was investigated in three experimental hypertensive models, viz, egg-fed diet, glucose-induced and cadmium-induced hypertensive rats. Cardiovascular parameters, including systolic blood pressure (SBP), diastolic blood pressure (DBP), mean blood pressure (MBP) and heart rate (HR) were measured by tail cuff method using non-invasive blood pressure apparatus (NIBP) attached. AMECT was also investigated for its phytochemical profile.Results: The results indicate that AMECT produced a dose-dependent, significant (p < 0.05) decrease in SBP, DBP, MBP, and HR (p < 0.01) of normotensive rats, when compared to control groups, at all test doses. The 500 mg/kg dose produced a highly significant effect (mm Hg, p < 0.001) in SBP (85.9 ± 7.2), DBP (71.86 ± 12.1), MBP (75.1 ± 11.7) and HR (238.08 ± 8.3 beats/min), in comparison to 100 and 300 mg/kg doses; therefore, 500 mg/kg was selected for antihypertensive test in egg-fed, glucose-induced and cadmium-treated hypertensive rats. Significant (p < 0.05) antihypertensive and negative chronotropic effects were observed in hypertensive models compared to their respective normal controls. Phytochemical analysis revealed the presence of tannins, alkaloids, phenolic compounds, cardiac glycosides and flavonoids.Conclusion: The findings indicate that Caralluma tuberculata possesses significant anti-hypentensive activity in rats.Keywords: Phytochemical profile, Antihypertensive, Cardiovascular, Caralluma tuberculata N.E.Br, Blood pressur

Antihypertensive Activity of Aqueous-Methanol Extract of Berberis Orthobotrys Bien Ex Aitch in Rats

Purpose: To investigate the hypotensive potential of Berberis orthobotrys Bien Ex Aitch (Family: Berberidaceae) in both normotensive and hypertensive rats.Methods: Aqueous-methanol (70:30) extract of Berberis orthobotrys at doses of 25, 50, 75 and 100 mg/kg was evaluated for its effect on blood pressure and heart rate using non-invasive blood pressure measuring apparatus. After initial screening, 100 mg/kg dose that produced a maximum effect was selected for the antihypertensive study. Median lethal dose (LD50) and sub-chronic toxicity of the extract were also determined. Various biochemical parameters and organ weight were measured usingstandard procedures.Results: The extract produced a significant (p < 0.01) decrease in systolic blood pressure (SBP), mean blood pressure (MBP), diastolic blood pressure (DBP) and heart rate of normotensive rats at all test doses with maximum effect at 100 mg/kg. Similarly, a significant antihypertensive and negative chronotropic effect was observed in both hypertensive models. LD50 of the extract was 200 mg/kg in mice. The extract also exhibited a reduction (p < 0.05) in serum alanine transaminase (ALT), aspartate aminotransaminase (AST), alkaline phosphatase (ALP), triglycerides and low density lipoprotein (LDL) levels while a significant (p < 0.05) increase in high density lipoproteins (HDL) level was observed.Conclusion: It seems that the aqueous-methanol extract of Berberis orthobotrys possesses active compounds which may be responsible for the antihypertensive and negative chronotropic effects in rats.Keywords: Berberis orthobotrys, Antihypertensive, Egg feed diet, Blood lipid

Pathoadaptive mutations of Escherichia coli K1 in experimental neonatal systemic infection

Although Escherichia coli K1 strains are benign commensals in adults, their acquisition at birth by the newborn may result in life-threatening systemic infections, most commonly sepsis and meningitis. Key features of these infections, including stable gastrointestinal (GI) colonization and age-dependent invasion of the bloodstream, can be replicated in the neonatal rat. We previously increased the capacity of a septicemia isolate of E. coli K1 to elicit systemic infection following colonization of the small intestine by serial passage through two-day-old (P2) rat pups. The passaged strain, A192PP (belonging to sequence type 95), induces lethal infection in all pups fed 2–6 x 106 CFU. Here we use whole-genome sequencing to identify mutations responsible for the threefold increase in lethality between the initial clinical isolate and the passaged derivative. Only four single nucleotide polymorphisms (SNPs), in genes (gloB, yjgV, tdcE) or promoters (thrA) involved in metabolic functions, were found: no changes were detected in genes encoding virulence determinants associated with the invasive potential of E. coli K1. The passaged strain differed in carbon source utilization in comparison to the clinical isolate, most notably its inability to metabolize glucose for growth. Deletion of each of the four genes from the E. coli A192PP chromosome altered the proteome, reduced the number of colonizing bacteria in the small intestine and increased the number of P2 survivors. This work indicates that changes in metabolic potential lead to increased colonization of the neonatal GI tract, increasing the potential for translocation across the GI epithelium into the systemic circulation

Prognostic model to predict postoperative acute kidney injury in patients undergoing major gastrointestinal surgery based on a national prospective observational cohort study.

Background: Acute illness, existing co-morbidities and surgical stress response can all contribute to postoperative acute kidney injury (AKI) in patients undergoing major gastrointestinal surgery. The aim of this study was prospectively to develop a pragmatic prognostic model to stratify patients according to risk of developing AKI after major gastrointestinal surgery. Methods: This prospective multicentre cohort study included consecutive adults undergoing elective or emergency gastrointestinal resection, liver resection or stoma reversal in 2-week blocks over a continuous 3-month period. The primary outcome was the rate of AKI within 7 days of surgery. Bootstrap stability was used to select clinically plausible risk factors into the model. Internal model validation was carried out by bootstrap validation. Results: A total of 4544 patients were included across 173 centres in the UK and Ireland. The overall rate of AKI was 14·2 per cent (646 of 4544) and the 30-day mortality rate was 1·8 per cent (84 of 4544). Stage 1 AKI was significantly associated with 30-day mortality (unadjusted odds ratio 7·61, 95 per cent c.i. 4·49 to 12·90; P < 0·001), with increasing odds of death with each AKI stage. Six variables were selected for inclusion in the prognostic model: age, sex, ASA grade, preoperative estimated glomerular filtration rate, planned open surgery and preoperative use of either an angiotensin-converting enzyme inhibitor or an angiotensin receptor blocker. Internal validation demonstrated good model discrimination (c-statistic 0·65). Discussion: Following major gastrointestinal surgery, AKI occurred in one in seven patients. This preoperative prognostic model identified patients at high risk of postoperative AKI. Validation in an independent data set is required to ensure generalizability