Artesunate effect on schistosome thioredoxin glutathione reductase and cytochrome c peroxidase as new molecular targets in schistosoma mansoni-infected mice / 生物医学与环境科学（英文）

<p><b>OBJECTIVE</b>To investigate the possible effect of artesunate (ART) on schistosome thioredoxin glutathione reductase (TGR) and cytochrome c peroxidase (CcP) in Schistosoma mansoni-infected mice.</p><p><b>METHODS</b>A total of 200 laboratory bred male Swiss albino mice were divided into 4 groups (50 mice in each group). Group I: infected untreated group (Control group) received a vehicle of 1% sodium carbonyl methylcellulose (CMC-Na); Group II: infected then treated with artesunate; Group III: infected then treated with praziquantel, and group IV: infected then treated with artesunate then praziquantel. Adult S. mansoni worms were collected by Animal Perfusion Method, tissue egg counted, TGR, and CcP mRNA Expression were estimated of in S. mansoni adult worms by semi-quantitative rt-PCR.</p><p><b>RESULTS</b>Semi-quantitative rt-PCR values revealed that treatment with artesunate caused significant decrease in expression of schistosome TGR and CcP in comparison to the untreated group. In contrast, the treatment with praziquantel did not cause significant change in expression of these genes. The results showed more reduction in total worm and female worm count in combined ART-PZQ treated group than in monotherapy treated groups by either ART or PZQ. Moreover, complete disappearance (100%) of tissue eggs was recorded in ART-PZQ treated group with a respective reduction rate of 95.9% and 68.4% in ART- and PZQ-treated groups.</p><p><b>CONCLUSION</b>The current study elucidated for the first time that anti-schistosomal mechanisms of artesunate is mediated via reduction in expression of schistosome TGR and CcP. Linking these findings, addition of artesunate to praziquantel could achieve complete cure outcome in treatment of schistosomiasis.</p>

Modulating effect of [Atorvastatin] on paraoxonasel [PON1] activity in type 2 diabetic Egyptian patients with or without nephropathy

The aim of this study was to investigate modulating effect of atorvastatin on serum paraoxonasel enzyme [PON1] activity in type 2 diabetic Egyptian patients with or without nephropathy. The present study was carried out on the following groups: thirty healthy persons were enrolled as [Control group], group I: twenty type 2 diabetic patients without nephropathy, group II: twenty type 2 diabetic patients with nephropathy. All the patients were selected to be under the antidiabetic regimen by insulin, and patients received antihypertensive agents were excluded from the follow up study to avoid drug interaction fallacies. Twenty two patients [15 without nephropathy and 7 with nephropatuy] received [atorvastatin] in individually adjusted oral dosage [range 10-20 mg] once/day for 12 weeks, All cases were subjected to thorough clinical examination and history taking and measurement of serum levels of: PON1 activity, malondialdehyde [MDA], glutathione reductase activity, fasting glucose, total cholesterol, triglycerides, high-density lipoprotein [HDL], low-density lipoprotein [LDL], urea and creatinine. Urine samples were collected for determination of proteinuria. The obtained results showed that PON1 activity and HDL significantly decreased and fasting glucose significantly increased in patients without [group I] and with nephropathy [group II] when compared to the control group, with significant difference in their levels between group II and group I MDA, total cholesterol and LDL levels significantly increased and glutathione reductase activity significantly decreased in group I and group II when compared to the control group. Urea, creatinine and proteinuria levels showed significant increase in patients with diabetic nephropathy [group II] when compared to control group and patients without nephropathy [group I], with non significant difference between control group and group I [Atorvastatin] therapy caused significant increase in PON1 activity and serum levels of MDA and glutathione reductase activity were significantly decreased and increased, respectively. Also, total cholesterol, triglycerides and LDL-cholesterol levels were significantly reduced with significant increase in HDL-cholesterol levels. There was significant modest reduction in serum urea and creatinine levels as well as proteinuria level. Fasting glucose level was significantly reduced under the antidiabetic regimen of insulin through the follow up period. PON1 activity showed significant negative correlation with glucose and LDL and significant positive correlation with HDL in the all studied groups. It could be concluded that [atorvastatin] by its pleiotropic effects could provide optimal therapeutic intervention to control not only dyslipidemia, but also oxidative stress status with consequent improvement in the course of type 2 diabetes and diabetic nephropathy. More specifically, restoration of PONl activity by [atorvastatin] open a window to investigate other drugs that could provide a new adjuvant therapeutic line for more control of diabetes and diabetic nephropathy. Further studies is also recommended to study distribution of PON1 genetic polymorphism among Egyptian population to explain variability in its activity and its relationship with other factors that associate diabetes and its complications

Role Of alpha- chymotrypsin and colchicine as adjuvant therapy in experimental muscular trichinellosis : parasitological, biochemical and immunohistochemical study

Muscular trichinellosis is a crippling disease, and it is not satisfactorily treated by the anti-parasitic drug albendazole. Trichinella spiralis larvae can survive for long time in muscle phase by formation of fibrous [collagenous] capsule around it, for their protection from host immune system. Colchicine, is a well known antifibrotic that is used long time ago in different fibrotic diseases, and proved recently to be safe for use even in long durations. Also, alpha-chymotrypsin is one member of proteinase enzymes that were proved to cause degradation of extracellular matrix components. So, this study aimed to investigate the effect of adding these antifibrotic agents to albendazole during treatment of muscular trichinellosis. The study was performed on 175 albino mice comprising 7 equal groups 25 mice each. Mice from groups I to VI were infected by T.spiralis larvae orally [200larvae / mouse], group VII served as the healthy non infected group for comparison of biochemical and immunohistochemical results. Group II was treated by albendazole alone orally for three successive days, groups III, IV were given alpha-chymotrypsin intramuscularly and colchicine orally respectively, for four weeks. Groups V,VI were given combined therapy of albendazole and alpha-chymotrypsin and albendazole and colchicine respectively for four weeks. Assessment of results was achieved through; parasitological, biochemical and immunohistochemical studies. Total larval count was done to all studied infected groups, measurement of tissue markers of fibrosis'' muscle hydroxyproline and [MMP-2]'', and also immunohistochemical staining of collagen type IV and fibronectin was done to both infected groups and the non infected one for comparison. Statistical analysis was performed to determine differences between studied groups in different measured parameters. In groups treated with combination therapy [albendazole and alpha-chymotrypsin, ''group V'' and albendazole and colchicine'' group VI''], there was a marked reduction in total larval count, reduction of muscular hydroxyproline levels, elevation of muscular MMP-2 when compared to the group treated with albendazole alone ''group II'', the differences were found to be statistically significant [p<0.05]. At the same time, the differences in the previously mentioned parameters were proved to be non significant statistically between group V and group VI. There was also a decrease in staining intensity of collagen type IV and fibronectin in groups received the antifibrotics[groups III to VI] in comparison to both groups I and II and the, there was a statistical positive correlation between hydroxyproline biochemical mean value and staining intensity [p<0.05]. Addition of antifibrotic drugs [alpha- chymotrypsin and colchicine] as adjuvant therapy to antiparasitic drugs in treatment of muscular trichinellosis could be a beneficial measure to improve treatment outcome by decreasing both numbers of larvae in the muscle, and fibrous tissue formation, which form together the backbone of pathology and crippling to the patient

Urinary creatinine and serum cystatin C in asthmatic children treated with inhaled corticosteroid and beta 2 agonist

L-arginine, an amino acid involved in the production of urea, creatinine and nitric oxide [NO] that is known to play an important role as an inflammatory mediator in the airways. Inhaled corticosteroids and beta [2] agonists are the most frequently prescribed medications in the management of chronic asthma. Current guidelines emphasis their complementary role. Although many patients use both drugs, there is little information on the effectiveness of their combination. In the present study we investigated the effect of a combination of glucocorticoids and beta [2] -agonists inhaled by asthmatics on the metabolism of L-arginine. Sixty-six children with mild-to moderate asthma were enrolled in this study and treated with different regimens of inhaled drugs but fifty three children only completed the study [Twenty one with inhaled beta [2] agonist [salmeterol], 15 with inhaled corticosteroid [fluticasone propionate], and 17 with a combination of inhaled salmeterol and fluticasone propionate]. Fifteen healthy-matched children served as a control group. Pulmonary function tests [forced expiratory volume in one second [FEV[1]], peak expiratory flow rate [PEFR]], methacholine challenge tests, serum cystatin C, 24 hours urinary measurement of urea, creatinine, nitrates, and urinary osmolality were performed before and after three months of the inhaled drug therapy. The results of this study demonstrated: [1] Non significant differences in serum cystatin C and urinary urea, creatinine, nitrates, osmolality were noted in asthmatic children vs control group. [2] non significant differences in serum cystatin C level and urine osmolality were observed in different groups before and after therapy. [3] compared to that before therapy, children treated by the combination of corticosteroid and beta [2] agonist had a significant higher level of urinary creatinine [p=0.0001] and a higher creatinine/urea ratio [c/u ratio] [p=0.0001] with significantly lower levels of urinary urea [p=0.002], and urinary nitrates [p=0.0001]. [4] in children treated by the combination of corticosteroid and beta [2] -agonist, there were a significant positive correlations between urinary creatinine and both FEV[1] [r= +0.699, p<0.01] and methacholine provocative dose causing a 20% fall in FEV[1] [R= +0.695, P< 0.01]. Also there were significant positive correlations between c/u ratio and both FEV[1] [r= +0.821, p = <0.01] and methacholine provocative dose causing a 20% fall in FEV[1] [r= +0.850, p< 0.01]. [5] in children treated with corticosteroid alone, only urinary nitrates was significantly lower after treatment as compared to that before treatment. [6] in children treated with beta [2] agonist alone, no significant differences in urinary urea, creatinine, nitrates and c/u ratio as compared to that before therapy. In asthmatic children, treatment with a combination of inhaled corticosteroid and beta [2] -agonist had a beneficial augmenting influence on the metabolism of L-arginine with better improvement of lung functions and bronchial hyperreactivity than treatment with either corticosteroid or beta [2] -agonist alone. Also creatininuria and urinary c/u ratio can be used as a simple and noninvasive parameters for assessment of response to treatment in these children. Also our results demonstrated normal serum cystatin C concentrations in asthmatic children in between attacks and remained unaffected by a therapy with inhaled corticosteroid, beta [2] agonist or a combination of both