Pyridazine and its related compounds. Part 35 [1]: Synthesis, characterization and antimicrobial activity of some novel pyridazine and triazolopyridazine containing sulfonamides

The present study describes the chemical synthesis and antimicrobial evaluation of some new pyridazine and triazolopyridazine derivatives. The structure assignments of the new compounds are based on chemical and spectroscopic evidences. The Study results showed that derivatives 6a, 6b, 6g and 6i have promising inhibitory activity against (Micrococcus luteus). Compound 6i has also noticeable inhibition activity against (Escherichia coli) and compound 3g show remarkable activity against (Candida albicans). Rest of compounds showed moderate to low activity against the examined microorganisms

ESTROGENS IMPROVE THE CARDIOVASCULAR ALTERATIONS IN FRUCTOSE-INDUCED INSULIN RESISTANT OVARIECTOMIZED RATS

Objective: The present study aimed to investigate the possible improving effects of 17-β estradiol (EST) and genistein (GEN) on the cardiovascular changes associated with fructose (21% in drinking water for 8 weeks)-induced insulin resistance.Methods: Sham-operated and ovariectomized mature female rats were included in this study. Insulin-resistant ovariectomized animals were sc treated with EST (100 µg/kg) or GEN (1 mg/kg) on the daily basis for 21 consecutive days.Results: Induction of insulin resistance in both sham-operated and ovariectomized rats decreased the vascular responsiveness of isolated aortic rings towards the vasoconstrictor norepinephrine and the vasodilator acetylcholine (Ach) with no changes towards the vasodilator sodium nitroprusside. Fructose-induced insulin resistance was also associated with an elevation in the blood pressure (BP) with decreased serum level of nitric oxide (NO). Treatment of insulin-resistant ovariectomized rats with either EST or GEN improved the vascular responsiveness of isolated aortic rings towards Ach and succeeded to reduce the elevated BP. Moreover, both EST and GEN decreased the insulin resistance/compensatory hyper insulinaemia. Treatment with EST increased serum NO level.Conclusion: EST and GEN have the ability to improve the endothelium-dependent relaxation in insulin-resistant ovariectomized rats and modulate the elevated BP.Â

Impact of Using Emulsifier with Different Calcium and Soybean Oil Levels on Broilers Performance and Minerals Deposition

This study aimed to evaluate the effect of emulsifiers with different calcium and soybean oil levels on Ross 308 broiler performance, digestibility, carcass quality traits, and deposition of calcium, phosphorus, and manganese on the body and tibia of broilers. A total of 360 one-day-old chicks were randomly distributed into 24 treatment groups: three calcium to phosphorus ratios were used, 2:1, 1.8:1, and 1.6:1, and each ratio was divided into two positive control treatments with an emulsifier (Lipidol) and a negative control without an emulsifier; moreover, each treatment used four levels of soybean oil: 1%, 1.5%, 2%, and 2.5%. The results showed that emulsifier supplementation, low calcium levels (1.8:1 and 1.6:1), and high oil levels (2% and 2.5%) significantly elevated (P < 0.05) body weight and body weight gain and reduced (P < 0.05) feed intake and feed conversion ratio in all stages, except for body weight gain and feed conversion ratio during the finisher period, which showed a nonsignificant difference. Moreover, broilers fed the diet with emulsifier had higher dressing and abdominal fat percentage (P < 0.0001) and those fed low Ca level (1.6:1) significantly (P < 0.0001) showed the highest abdominal fat percentage. It can be concluded that an emulsifier with a low oil level could improve fat digestibility in broiler chickens. Furthermore, decreasing the level of calcium at a rate of 1.6:1 can improve fat digestibility and elevate (P < 0.0001) the level of cholesterol on day 10; however, on days 23 and 42, cholesterol level was elevated by high calcium level (2:1). Emulsifier also elevates the cholesterol level at days 10 and 42. Broilers fed emulsifier, low oil level (1%), and high calcium levels at rates of 1.8:1 and 2:1 significantly (P < 0.05) had elevating levels of calcium and phosphorus and decreased manganese levels on the broiler body and tibia

Design and Synthesis of Novel Pyrazole-Substituted Different Nitrogenous Heterocyclic Ring Systems as Potential Anti-Inflammatory Agents

With the aim of developing novel anti-inflammatory scaffolds, a new series of pyrazole-substituted various nitrogenous heterocyclic ring systems at C-4 position were synthesized through different chemical reactions and validated by means of spectral and elemental data. The new obtained compounds were investigated for their anti-inflammatory activity using the carrageenan-induced paw edema standard technique and revealed that, compound 6b showed increased potency with % inhibition of edema 85.23 ± 1.92 and 85.78 ± 0.99, respectively, higher than the standard reference drugs indomethacin and celebrex (72.99% and 83.76%). Molecular modeling studies were initiated herein to validate the attained pharmacological data and provide understandable evidence for the observed anti-inflammatory behavior

Streptozotocin-induced vascular and biochemical changes in rats: Effects of rosiglitazone vs. metformin

The aim was to investigate rosiglitazone and metformin effects on some vascular and biochemical changes associated with streptozotocin (55 mg/kg; i.p.)-induced hyperglycaemia in rats. Isolated aortas were used to evaluate their reactivity towards norepinephrine, acetylcholine, and sodium nitroprusside. Blood samples were used to assess the biochemical changes of some parameters viz., plasma lipid peroxides and nitric oxide levels and erythrocytic glutathione peroxidase activity. Hyperglycaemic animals orally received rosiglitazone (0.5 mg/kg) or metformin (150 mg/kg) daily for 2 weeks and their effects were determined 24 h after the last dose. Our results revealed that streptozotocin-induced hyperglycaemia is associated with impaired vascular reactivity towards various agents, increased lipid peroxides level, decreased glutathione peroxidise activity, and decreased nitric oxide level. Both drugs further decreased norepinephrine-induced contraction and improved acetylcholine- and sodium nitroprusside-induced relaxations. Rosiglitazone restored the alterations in all tested biochemical parameters while metformin restored only glutathione peroxidise activity. In conclusion both drugs show beneficial effects against the vascular dysfunction associated with hyperglycaemia which might be related to their euglycaemic activity in addition to anti-oxidant property of rosiglitazone and a direct effect of metformin on vascular smooth muscle

Detailed radiographic evaluation of articular damage.

<p>Data are presented as mean ± SEM.</p><p>n = 10.</p><p>a: significantly different from CIA-group at <i>p</i><0.05.</p><p>b: significantly different from LEF-group at <i>p</i><0.05.</p><p>Detailed radiographic evaluation of articular damage.</p

Intra-articular MPO activity.

<p>Mice with CIA were treated with leflunomide (LEF), nimesulide (NIM), or leflunomide+nimesulide (LEF+NIM) and compared to untreated arthritic and normal mice. Articular MPO activity was measured 40 days after treatment as a marker of leucocytic infiltration.</p

Symptomatic assessment of arthritis.

<p>Mice with CIA were treated with leflunomide (LEF), nimesulide (NIM), or leflunomide+nimesulide (LEF+NIM) and compared to untreated arthritic and normal mice. Hyperalgesia (A) and joint stiffness (B) were recorded at pre-arthritic, mid-arthritic and late arthritic phases of arthritis and compared to base line readings. Data are presented as mean ± SD. * Significantly different from normal mice; ** significantly different from CIA-mice.</p