Propofol pharmacokinetics in infants

Infant and children differ markedly from adult patients. Since the production of propofol, it has gained popularity as an agent for both induction and maintenance of anaesthesia for adults and children. There has been a lack of pharmacokinetic studies in children less than 3 years. Was to determine the complete pharmacokinetic profile of propofol in infants [2-24 months]. Forty eight patients were randomly assigned into 4 groups, each group has 12 patients. They were scheduled to undergo superficial body surgery of I hour expected duration. Venous blood samples were collected and analyzed used high performance liquid chromatography [HPLC].Non linear mixed effects modelling [NONMEM] software program was used to analyze the pharmacokinetic data. The pharmacokinetic of propofol in infants followed two compartement model with systemic clearance -[Cl] 29.77 +/- 9.46 ml kg[-1] min[-1], central volume of distribution [Vc] 0.62 +/- 0.24 l kg[-1], and the volume at steady state [Vss] 1.67 +/- 0.26 l kg[-1]. The context sensitive half life [HL] was 0.24 +/- 0.02 h. The infants have a larger volume of distribution and a higher clearance of propofol. Therefore, the induction and maintenance doses should be increased in this young age with using population based pharmacokinetic parameters for accurate propofol dosing strategy

Do desipramine and fluoxetine ameliorate the extent of colonic damage induced by acetic acid in rats?

The present study was aimed to compare the anti-inflammatory and antioxidant effects of two antidepressant drugs; desipramine and fluoxetine, administered in two different doses, on experimentally induced colitis in rats. Two doses for each drug [10, 20 mg/kg/d] were injected intraperitoneally in forty eight adult male albino rats for 2 weeks after induction of colitis by intra-colonic administration of 2ml 3% acetic acid. Several parameters including, macroscopic [ulcer score index], microscopic [histological] and biochemical such as myeloperoxidase [MPO], reduced glutathione [GSH], tumor necrosis factor alpha [TNF-alpha] and interleukin-1 Beta [IL-1beta] were measured using standard assay procedures. The study demonstrated that both desipramine and fluoxetine significantly attenuated the extent and the severity of the macroscopic and microscopic histological signs of cell damage. Both drugs significantly reduced tissue MPO activity in a dose dependent manner. Both desipramine and fluoxetine at either dose increased significantly the GSH in colonic tissue. On the contrary, both desipramine and fluoxetine significantly reduced TNF-alpha and IL-beta in a dose dependent manner. However, desipramine at the dose of 20 mg/kg produced more decrease in the level of TNF-alpha compared to the effect of the smaller dose, and on the contrary, fluoxetine at the dose of 10 mg/kg showed more decrease in the level of IL-beta compared to the effect of the larger dose. The available data indicate that both desipramine and fluoxetine have anti-inflammatory and antioxidants effects in experimentally induced colitis in rats opening the avenue to their possible protective role in patients with inflammatory bowel disease

Role of modulation of vascular endothelial growth factor and tumor necrosis factor-alpha in gastric ulcer healing in diabetic rats

To assess the role of modulation of vascular endothelial growth factor and tumor necrosis factor-alpha in gastric ulcer healing in streptozotocin [STZ]- induced diabetic rats. forty male rats were made diabetic by intraperitoneal [i.p] STZ infection and ten rats were injected i.p. by a single dose of saline and served as a control for group II Six weeks following STZ or saline injection, gastric ulcers were induced by serosal application of acetic acid. Three days after acetic acid application, rats were divided into: group I[normal control], group II [STZ-injected rats], groups III. IV and V [STZ-injected rats treated with insulin, insulin and phosphodiesterase [PDE] inhibitor [pentoxifylline] [PTX] and insulin and Hydroxymethylglutaryl Coenzyme A [HMG-CoA] reductase inhibitor [simvastatin] respectively, for seven days following acetic acid application. At the end of the experimental period, plasma glucose was measured. Gastric ulcer area as well as gastric tumor necrosis factor- alpha [TNF-alpha], vascular endothelial growth factor [VEGF] and haemoglobin [Hb] concentrations were determined. STZ-injection induced diabetes, evidenced by significant higher mean value in plasma glucose concentration in group II compared to that of the control group [I] Significant delay in ulcer healing could be observed, in the form of significant increase in gastric ulcer area in group II compared to the control group I. STZ-injection resulted in significant increase in gastric TNF-alpha as well as a significant decrease in gastric VEGF concentrations together with a significant decrease in gastric angiogenic response evidenced by a significant decrease in gastric Hb concentration in group II compared to the control group I. The use of insulin, as well as combinations of insulin and PTX or simvastatin caused a significant decrease in plasma glucose concentration as well as a significant increase in gastric ulcer healing [evidenced by a significant decrease in ulcer area], gastric VEGF and gastric Hb concentration as well as significant decrease in gastric TNF-alpha compared to group II. A significant difference in gastric ulcer area and gastric TNF-alpha could be observed between rat that received combinations of insulin and PTX or simvastatin compared to rats that received insulin only. A significant difference in gastric VEGF and Hb was also found between the group that received combination of insulin and simvastatin compared to the group that received insulin only. Experimental DM impairs ulcer healing, depending upon the increased release of proinflammatory cytokines [e.g. TNF-alpha] and the attenuation of angiogenesis Insulin reversed this impairment of ulcer healing in diabetic rats, mainly due to the enhancement of angiogenesis and reduction in expression of TNF-alpha in the ulcer area. Phosphodiesterase [PDE] inhibitor [pentoxifylline], via suppressing TNF-alpha and hydroxymethylglutaryl coenzyme A [HMG-CoA] reductase inhibitor [simvastatin]. via suppressing TNF-alpha and increasing VEGF, are beneficial in enhancing gastric ulcer healing. These findings support the notion that impairment of healing of gastric ulcers in DM results from impairment of angiogenic response of the gastric mucosa to injury together with upregulotion of gastric TNF-alpha and suggest the feasibility of a novel treatment strategy for patients in whom impairment of ulcer healing complication of DM

ACE inhibitors or ATI antagonists protect against an experimental model of pulmonary fibrosis in rats?

A common side effect to cytotoxic antibiotic bleomycin [BLM] is interstitial pneumonitis with progressive pulmonary fibrosis. At the same time, some of the angiotensin renin system [RAS] inhibitors are reported to have anti-inflammatory in addition to their antihypertensive effects. This study investigated the potential anti-inflammatory effect of angiotensin converting enzyme inhibitors captopril and enalapril and angiotensin receptor blockers losartan and candesartan on experimental BLM-induced acute lung injury in rats. BLM-induced lung injury was assessed by the total white cell count, neutrophil count and interleukin-8 [IL-8] in bronchoalveolar lavage [BAL] fluid and serum level of tumor necrosis factor-alpha [TNF- alpha]. In addition, oxidative stress in lung tissue was measured by tissue contents of malondialdehyde [MDA] and reduced glutathione [GSH], enzymatic activity of superoxide dismutase [SOD] and catalase [CAT] in lung homogenate. A single intravenous dose of BLM was given on day 14[th] of the study. The four investigated RAS inhibitors [Captopril, enalapril, losartan and candesartan] were examined in two different regimens. The first regimen [a] was to start the RAS inhibitor on day 14[th] of the study with BLM and to continue for one week after BLM. In the second regimen [b], the RAS was started 2 weeks prior to BLM and continued for one week thereafter. Administration of candesartan was accompanied with significant decrease in the total white cell and neutrophil counts. Further, significantly lower counts were found when the drug was started two weeks prior to induction of BLM-lung injury [regimen b] compared to its introduction with BLM on day 14[th] [regimen a] [p<0.001]. The associated lower level of IL-8 in BAL in all RAS inhibitors groups failed to reach level of statistical significance compared to BLM control injury [p>0.05]. However, the level of TNF-alpha in serum was decreased significantly in all RAS inhibitors-treated groups. Significant higher lung tissue content of GSH with all RAS treated groups - especially with captopril, there was a significant difference between regimen a and b- compared to BLM-injury control group. There was a significant lower activation of SOD and CAT and less MDA content with all RAS inhibitors treated groups than BLM-injury control group [p<0.001]. All the investigated drugs exhibited significant anti-inflammatory and antioxidant effect especially the prophylactic regimen with captopril. Candesartan was the only drug that affects the macrophage mobility and its chemotactic activity

Study of possible effects of hormonal therapy on experimentally induced colitis in rats

Both beneficial and detrimental effects have been ascribed to sex steroids. In relation to gut inflammation, data is relatively limited. This study was designed to examine the influence of hormonal environment on severity of mucosal injury, level of interleukin 10 and oxidative stress in experimental colitis in ovariectomized rats. Sixty female albino rats were used in this work; 40 rats were bilaterally ovariectomized [Ovx] and 2 weeks thereafter; colitis was induced by intra-colonic administration of 2ml 3% acetic acid. Ten rats were sham-operated and served as a control normal group. The remaining 10 rats underwent colitis only and served as acetic acid-induced [AAI] colitis control untreated group. The Ovx rats were randomly divided into 4 groups [n=10 each] as follows: Ovx-AAI colitis, estrogen-, progesterone- and tamoxifen- treated Ovx-AAI colitis. The colitis, Ovx-AAI colitis and tamoxifen groups showed grossly and microscopically evident colon mucosal injury [significantly increased ulcer score index], oedema [increased weight of distal colon], inflammatory cell infiltration, increased activity of myeloperoxidase enzyme [MPO], increased tissue malondialdehyde [MDA] and reduced glutathione [GSH] depletion compared to sham group. The Ovx-AAI colitis group showed more significant impairment in all the fore mentioned parameters as compared to the colitis group. The estrogen and progesterone treated Ovx-AAI colitis groups showed less impairment of all parameters used to assess colon mucosal injury, inflammatory response and oxidative stress compared to the non-treated counterpart. A significant decrease in the level of IL-10 was found in the colitis, Ovx-AAI colitis and Tamoxifen groups compared to sham operated group. The level of this cytokine in the estrogen and progesterone groups was comparable to that of the sham-operated group. Decline of IL-10 level may underlie the currently observed enhancement of colon inflammation and oxidative stress in female rats deprived from endogenous and exogenous female sex steroids. Estrogen and progesterone replacement therapy has been associated with restored level of this cytokine and decreased susceptibility to colon inflammation while the anti-estrogen analog tamoxifen lacks such effects