Biological activity of synthesized 5-{1-[(4-chlorophenyl)sulfonyl]piperidin-4-yl}-2-mercapto-1, 3, 4-oxadiazole derivatives demonstrated by in silico and BSA binding studies

We synthesized a series of compounds bearing pharmacologically important 1,3,4-oxadiazole and piperidine moieties. Spectral data analysis by 1H-NMR, 13C-NMR, IR and EI-MS was used to elucidate the structures of the synthesized molecules. Docking studies explained the different types of interaction of the compounds with amino acids, while bovine serum albumin (BSA) binding interactions showed their pharmacological effectiveness. Antibacterial screening of these compounds demonstrated moderate to strong activity against Salmonella typhi and Bacillus subtilis but only weak to moderate activity against the other three bacterial strains tested. Seven compounds were the most active members as acetyl cholinesterase inhibitors. All the compounds presented displayed strong inhibitory activity against urease. Compounds 7l, 7m, 7n, 7o, 7p, 7r, 7u, 7v, 7x and 7v were highly active, with respective IC50 values of 2.14±0.003, 0.63±0.001, 2.17±0.006, 1.13±0.003, 1.21±0.005, 6.28±0.003, 2.39±0.005, 2.15±0.002, 2.26±0.003 and 2.14±0.002 µM, compared to thiourea, used as the reference standard (IC50 = 21.25±0.15 µM). These new urease inhibitors could replace existing drugs after their evaluation in comprehensive in vivo studies.

Functional roles of sodium-calcium exchange in autorhythmicity and action potential of murine fetal cardiomyocytes at early developmental stage / 生理学报

The aim of the present paper was to study the role of sodium calcium exchanger (NCX) in the generation of action potentials (APs) in cardiomyocytes during early developmental stage (EDS). The precisely dated embryonic hearts of C57 mice were dissected and enzymatically dissociated to single cells. The changes of APs were recorded by whole-cell patch-clamp technique before and after administration of NCX specific blockers KB-R7943 (5 μmol/L) and SEA0400 (1 μmol/L). The results showed that, both KB-R7943 and SEA0400 had potent negative chronotropic effects on APs of pacemaker-like cells, while such effects were only observed in some ventricular-like cardiomyocytes. The negative chronotropic effect of KB-R7943 on ventricular-like cardiomyocytes was accompanied by shortening of AP duration (APD), whereas such an effect of SEA0400 was paralleled by decrease in velocity of diastolic depolarization (Vdd). From embryonic day 9.5 (E9.5) to E10.5, the negative chronotropic effects of KB-R7943 and SEA0400 on ventricular-like APs of embryonic cardiomyocytes gradually disappeared. These results suggest that, in the short-term development of early embryo, the function of NCX may experience developmental changes as evidenced by different roles of NCX in autorhythmicity and APs generation, indicating that NCX function varies with different conditions of cardiomyocytes.

SPA0355 prevents ovariectomy-induced bone loss in mice

Estrogen withdrawal in post-menopausal women leads to overactivation of osteoclasts, which contributes to the development of osteoporosis. Inflammatory cytokines are known as one of mechanisms of osteoclast activation after estrogen deficiency. SPA0355 is a thiourea derivative that has been investigated for its antioxidant and anti-inflammatory activities. However, its efficacy in bone resorption has not been previously investigated. The aim of this study was to investigate the impact of SPA0355 on the development of osteoporosis and to explore its mode of action. In vitro experiments showed that SPA0355 inhibited receptor activator of NF-κB ligand (RANKL)-induced osteoclastogenesis in primary bone marrow-derived macrophages. This effect appears to be independent of estrogen receptor activation as ICI 180,782 failed to abrogate its effects on osteoclasts. Further signaling studies revealed that SPA0355 suppressed activation of the MAPKs, Akt, and NF-κB pathways. SPA0355 also increased osteoblastic differentiation, as evidenced by its effects on alkaline phosphatase activity and mineralization nodule formation. Intraperitoneal administration of SPA0355 to ovariectomized mice prevented bone loss, as verified by three-dimensional images and bone morphometric parameters derived from µCT analysis. Noticeably, SPA0355 did not show hepatotoxicity and nephrotoxicity and also had little effect on hematological parameters. Taken together, the results indicate that SPA0355 may protect against bone loss in ovariectomized mice by stimulation of osteoblast differentiation and by inhibition of osteoclast resorption. Therefore, SPA0355 is a safe and potential candidate for management of postmenopausal osteoporosis.

Synthesis, characterization, antioxidant and brine shrimp cytotoxic activity of novel 3-benzothioyl-l-[3-hydroxy-3-phenyl -3-propyl]-l-methylthiourea

In the present research work novel ephedrine based thiourea derivative, 3-benzothioyl-l-[3-hydroxy-3-phenyl -3-propyl]-l-methylthiourea 4is synthesized and then characterized elemental analyzed via various techniques i.e., Proton NMR, carbon13 NMR and fatherly confirmed via X-ray crystallography. Compound 4 was then screened for their possible antioxidant and cytotoxic potentials. Benzoyl chloride was treated with an equimolar potassium thiocyanate in acetone to achieve benzoyl isothiocyantes. It was then treated with an equimolar [1R, 2*S]-[-]-Ephedrine to obtain the 3-benzothioyl-l-[3-hydroxy-3-phenyl-3-propyl]-l-methyl thiourea4. It was then screened for antioxidant and cytotoxic potentials. The compound 4 showed excellent antioxidant activity almost comparable to ascorbic acid [standard] and have significant cytotoxic activity with LC[50] value 05+/-0.58 ppm

Effect of S-methyl-l-thiocitrulline dihydrochloride on rat micturition reflex

ABSTRACT Objective: To evaluate the effect of neuronal nitric oxide synthase on the striated urethral sphincter and the urinary bladder. Materials and Methods: A coaxial catheter was implanted in the proximal urethra and another one in the bladder of female rats, which were anesthetized with subcutaneous injection of urethane. The urethral pressure with saline continuous infusion and bladder isovolumetric pressure were simultaneously recorded. Two groups of rats were formed. In group I, an intrathecal catheter was implanted on the day of the experiment at the L6-S1 level of the spinal cord; in group II, an intracerebroventricular cannula was placed 5-6 days before the experiment. Results: It was verified that the group treated with S-methyl-L-thio-citrulline, via intrathecal pathway, showed complete or partial inhibition of the urethral sphincter relaxation and total inhibition of the micturition reflexes. The urethral sphincter and the detrusor functions were recovered after L-Arginine administration. When S-methyl-L-thio-citrulline was administered via intracerebroventricular injection, there was a significant increase of urethral sphincter tonus while preserving the sphincter relaxation and the detrusor contractions, at similar levels as before the use of the drugs. Nevertheless there was normalization of the urethral tonus when L-Arginine was applied. Conclusions: The results indicate that, in female rats anaesthetized with urethane, the nNOS inhibitor administrated through the intrathecal route inhibits urethral sphincter relaxation, while intracerebroventricular injection increases the sphincter tonus, without changing bladder function. These changes were reverted by L-Arginine administration. These findings suggest that the urethral sphincter and detrusor muscle function is modulated by nitric oxide.

Protective effects of salubrinal on liver injury in rat models of brain death / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Previous studies have indicated that endoplasmic reticulum stress participates in and mediates liver injury and apoptosis in brain-dead (BD) rats. In this study, we observed the effect of salubrinal (Sal, Sigma, USA) on liver cells in BD rats and explored its relevant mechanisms.</p><p><b>METHODS</b>Thirty Sprague-Dawley rats were equally randomized into three groups: BD group, Sal group, and DMSO group. The BD models were established by increasing intracranial pressure in a modified, slow, and intermittent way. In the drug groups, Sal was administered 1 h before the induction of BD. After modeling was completed, the blood and liver samples were harvested. CHOP and Caspase-12 mRNA expression was detected using quantitative polymerase chain reaction. PKR-like ER kinase (PERK), P-eukaryotic translation initiation factor 2α (eIF2α), eIF2α, CHOP and caspase-12 expression was detected using western blotting (WB). CHOP and caspase-12 distribution and expression in liver tissues were determined using immunohistochemistry (IHC). Alanine aminotransferase and aspartate aminotransferase level were detected using an automatic biochemical analyzer. Hepatic cell apoptosis was detected using TUNEL. The results were analyzed using Quantity-one v4.62 software (Bio-Rad, USA).</p><p><b>RESULTS</b>CHOP and caspase-12 expression and PERK, eIF2α, and P-eIF2α protein expression showed no significant difference between BD group and DMSO group. Compared with BD group, Sal group had a significantly higher P-eIF2C level and a lower P-PERK level 2 h and 6 h after BD (P < 0.05). However, eIF2α expression showed no significant difference (P > 0.05). After the Sal treatment, CHOP and caspase-12 mRNA expression significantly decreased 4 h after BD (P < 0.05). WB and IHC indicated that CHOP and caspase-12 expression also significantly decreased after Sal treatment. Sal was associated with improved liver function and decreased hepatic cell apoptosis.</p><p><b>CONCLUSIONS</b>Sal can significantly reduce apoptosis in hepatic cells of BD rats. This protective effect may be achieved via the PERK-eIF2α signaling pathway.</p>

SPA0355 attenuates ischemia/reperfusion-induced liver injury in mice

Hepatic ischemia/reperfusion (I/R) injury leads to oxidative stress and acute inflammatory responses that cause liver damage and have a considerable impact on the postoperative outcome. Much research has been performed to develop possible protective techniques. We aimed to investigate the efficacy of SPA0355, a synthetic thiourea analog, in an animal model of hepatic I/R injury. Male C57BL/6 mice underwent normothermic partial liver ischemia for 45 min followed by varying periods of reperfusion. The animals were divided into three groups: sham operated, I/R and SPA0355 pretreated. Pretreatment with SPA0355 protected against hepatic I/R injury, as indicated by the decreased levels of serum aminotransferase and reduced parenchymal necrosis and apoptosis. Liver synthetic function was also restored by SPA0355 as reflected by the prolonged prothrombin time. To gain insight into the mechanism involved in this protection, we measured the activity of nuclear factor-kappaB (NF-kappaB), which revealed that SPA0355 suppressed the nuclear translocation and DNA binding of NF-kappaB subunits. Concomitantly, the expression of NF-kappaB target genes such as IL-1beta, IL-6, TNF-alpha and iNOS was significantly downregulated. Lastly, the liver antioxidant enzymes superoxide dismutase, catalase and glutathione were upregulated by SPA0355 treatment, which correlated with the reduction in serum malondialdehyde. Our results suggest that SPA0355 pretreatment prior to I/R injury could be an effective method to reduce liver damage.

A QSAR study on a series of thiourea derivatives acting as anti-hepatitis C virus agents.

A quantitative structure-activity relationship (QSAR) study was performed on a large series of thiourea derivatives reported by Kang et al. [Bioorg Med Chem Lett (2009), 19, 1950-55 & 6063-68], acting as anti-hepatitis C virus (anti-HCV) agents. The activity of the compounds was found to be significantly correlated with their hydrophobic property and three indicator variables I1, I2 and I3, the first two specifying a negative effect of an alkyl and an aromatic group, respectively on their R-moiety and the third one specifying a negative effect of their Ar-moiety having a nitrogen-containing heterocyclic ring. The whole set containing 85 compounds was divided into two subsets: the training set and the test set containing 61 and 24 compounds, respectively. For the training set, the correlation coefficient (r) and the square of cross-validated correlation coefficient (r2cv) were found to be 0.926 and 0.83, respectively. The correlation obtained suggested that anti-HCV activity of the compounds would depend on their hydrophobic property, conformational flexibility and the steric effects of an alkyl or an aromatic group on the R-moiety. This suggested that the molecules might have significant hydrophobic interactions with the receptor which might be aided by their conformational flexibility, but hindered sterically by an alkyl or an aromatic group on their R-moiety. Using the correlation obtained, some new compounds having activity higher (>8.0) than the most active compound in the existing series were predicted.

The efficacy of SPA0355 in protecting beta cells in isolated pancreatic islets and in a murine experimental model of type 1 diabetes

Cytokines activate several inflammatory signals that mediate beta-cell destruction. We recently determined that SPA0355 is a strong anti-inflammatory compound, thus reporting its efficacy in protecting beta cells from various insults. The effects of SPA0355 on beta-cell survival were studied in RINm5F cells and primary islets. The protective effects of this compound on the development of type 1 diabetes were evaluated in non-obese diabetic (NOD) mice. SPA0355 completely prevented cytokine-induced nitric oxide synthase (iNOS) expression and cytotoxicity in RINm5F cells and isolated islets. The molecular mechanism of SPA0355 inhibition of iNOS expression involves the inhibition of nuclear factor kappaB and Janus kinase signal transducer and activator of transcription pathways. The protective effects of SPA0355 against cytokine toxicity were further demonstrated by normal insulin secretion and absence of apoptosis of cytokine-treated islets. In experiments with NOD mice, the occurrence of diabetes was efficiently reduced when the mice were treated with SPA0355. Therefore, SPA0355 might be a valuable treatment option that delays the destruction of pancreatic beta cells in type 1 diabetes.

Inhibitory Effect of SPA0355, a Thiourea Analogue, on Inflammation and Alveolar Bone Loss in Rats with Ligature-Induced Periodontitis

It has been documented that SPA0355 exerts anti-inflammatory effects via the inhibition of nuclear factor-kappaB activation. In present study, we investigated the inhibitory effects of SPA0355 on periodontitis in an animal model. Periodontitis was induced by ligation of the cervix of the 1st molar in the left mandible in rats. After ligature, the rats were randomly divided into four groups and topically applied with SPA0355 (0.5, 1, and 2%) or the vehicle alone once daily for 10 days. Body weight and food intake were measured daily throughout the experimental period. At day 10 post-ligature, the infiltration of inflammatory cells and distance of the cementoenamel junction (CEJ) to the alveolar bone crest (ABC) in the distal area of ligatured tooth were estimated histopathologically. No changes in body weight or food intake were found between the control and SPA0355 groups. The degree of inflammation was decreased in all three SPA0355 application groups. A decrease CEJ-ABC distance was observed in the 0.5% and 1% SPA0355 groups. These results indicate that SPA0355 inhibits the infiltration of inflammatory cells and alveolar bone resorption and suggests its potential as a therapeutic agent for periodontitis.

Synthesis and biological evaluation of sorafenib thiourea derivatives / 药学学报

Basing on the market multi-target antitumor agent sorafenib, a series of sixteen 4-[4-(2-methyl-aminoacyl-pyridyl)]oxylphenyl aryl thiourea derivatives were designed and synthesized. Their structures were identified by the spectra of 1H NMR, MS and elemental analysis. The evaluation of antitumor bioactivities in vitro was done by MTT method. It was shown that the synthesized compounds had antitumor activities and compounds 1a, 1d, 1i and 1j showed better or equal antitumor activity on sorafenib.

[Effects of the activation of histamine H3 receptors on the locomotor activity induced by dopaminergic treatment in the reserpine-treated rat model of Parkinson's disease]

The present study was designed to investigate the effects of the activation of histamine H3 receptors, by selective agonist, on dopaminergic treatment-induced locomotor behavior in a rat model of Parkinson's disease and L-DOPA-induced dyskinesia. Imetit, histamine H3 receptor agonist reduced the enhanced locomotor activity induced by L-DOPA 100 and 200 mg/kg, in a dose-dependent manner. The number of horizontal counts, following the injection of Imetit 7 mg/kg in combination with L-DOPA 200 mg/kg in reserpinised rats, was 1040 +/- 274 count/2h, which was significantly reduced compared to the horizontal activity following the injection of L-DOPA 200 mg/kg alone in reserpinised rats. The vertical count was significantly reduced by injection of imetit 7 mg/kg in combination with L-DOPA 200 mg/kg [560 +/- 110 count/2h]. The highest dose of Imetit 7 mg/kg that extensively reduced all locomotor parameters tested, did not significantly modify the increase in horizontal or vertical activity produced by quinpirole dopamine D2 agonist. The data suggest that histamine H3 receptor agonists can modulate the behavioural effects of L-DOPA, and may be useful for the treatment of the dyskinesia associated with long-term L-DOPA treatment of Parkinson's disease

Effect of H3R agonist, IMETIT on allergic rhinitis in guinea pigs / 临床耳鼻咽喉头颈外科杂志

OBJECTIVE@#To discuss the treatment of H3R agonist, IMETIT, on the allergic rhinitis(AR) ,and the influence to mRNA of Substance P(SP) and Substance P Receptor (SP-R) in AR model of guinea pigs.@*METHOD@#The severity of AR was assessed by allergic symptoms (sneezing, nasal rubbing and nose blocking). The changes in the nasal mucosa were studied by pathological methods. The expression of SP positive cell was detected by immunohistochemistry, and the expression of SP-R mRNA was detected by reverse transcriptive polymerase chain reaction (RT-PCR).@*RESULT@#Histamine H3R agonists, IMETIT can effectively improve the AR symptoms, sneezing, nasal itching, nasal congestion, reduce the pathological changes in the nasal mucosa, cut down the SP secretion and SP-R mRNA expression.@*CONCLUSION@#Histamine H3R agonist, IMETIT can effectively relieve the symptoms of AR in guinea pigs, which is related to reducing SP secretion and SP-R mRNA expression.

Substance P and its receptors are involved in the effect of histamine H3 receptor agonist, IMETIT on nasal allergic symptoms in guinea pigs / 中华耳鼻咽喉头颈外科杂志

<p><b>OBJECTIVE</b>To explore the influence of histamine H3 receptor agonist, IMETIT and simultaneous use of IMETIT and H1-receptor antagonist, Loratadine, on the symptoms of allergic rhinitis (AR) and substance P(SP) secretion and expression of SP receptor (SP-R) mRNA in AR model in guinea pigs.</p><p><b>METHODS</b>Guinea pigs were divided randomly into 4 groups: AR group (group A), IMETIT group (group B), Loratadine group (group C) and IMETIT+Loratadine group (group D). The severity of AR was assessed by determining the extent of three markers of allergic symptoms (sneezing, nasal rubbing and nose blocking). The changes in the nasal mucosa were studied by pathological methods. The expression of positive cell of SP was detected by immunohistochemistry. SP-R mRNA expression in nasal mucosa was used to do reverse transcriptive-polymerase chain reaction (RT-PCR). Statistical analysis was performed using a SPSS 13.0 software.</p><p><b>RESULTS</b>In Group B, the mean (x ± s) number of sneeze [(15.0 ± 1.3) times], scratching nose [(16.5 ± 2.3) times] and respiratory frequency [(76.3 ± 4.1) times/min] were significantly improved than those in group A [(23.5 ± 2.6) times, (26.1 ± 4.1) times and (66.5 ± 5.8) times/min, respectively), P value were 0.000, 0.000 and 0.001, respectively]. The numbers of SP-positive cells [(11.6 ± 3.6)/HP] and SP-R mRNA expression (0.64 ± 0.04) in group B were reduced significantly compared to group A [(27.1 ± 9.7)/HP, (0.83 ± 0.03), P value were 0.000, 0.000, respectively]. Sneeze [(10.0 ± 2.3) times], scratching nose [(11.8 ± 1.7) times] and respiration [(90.0 ± 5.0) times/min] in Group D were improved significantly than those in group B (P value were 0.000, 0.002 and 0.000, respectively). SP-positive cells [(2.0 ± 1.7)/HP] and SP-R mRNA expression (0.52 ± 0.06) in Group D compared with group B were also significantly reduced (P value were 0.012 and 0.000, respectively). Pathological changes in guinea pig nasal mucosa in group B, group D were alleviated than those in group A. The combination of IMETIT and Loratadine had a synergistic effect on these effects (F value were 11.59, 8.28, 5.61, 5.48, 6.50, respectively, P value were 0.002, 0.008, 0.025, 0.027, 0.017).</p><p><b>CONCLUSIONS</b>IMETIT and the combination of IMETIT with Loratadine can effectively relieve the symptoms of AR in guinea pigs, its mechanism may be relevant to reduce SP secretion and the expression of SP-R mRNA, and the two has a synergistic effect. It may be useful as a novel therapeutic approach in nasal allergy.</p>

Cytotoxic Activity and Structure Activity Relationship of Ceramide Analogues in Caki-2 and HL-60 Cells

B13, a ceramide analogue, is a ceramidase inhibitor and induces apoptosis to give potent anticancer activity. A series of thiourea B13 analogues was evaluated for their in vitro cytotoxic activities against human renal cancer Caki-2 and leukemic cancer HL-60 in the MTT assay. Some compounds (12, 15, and 16) showed stronger cytotoxicity than B13 and C6-ceramide against both tumor cell lines, and compound (12) gave the most potent activity with IC50 values of 36 and 9 microM, respectively. Molecular modeling of thiourea B13 analogues was carried out by comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA). We obtained highly reliable and predictive CoMSIA models with cross-validated q2 values of 0.707 and 0.753 and CoMSIA contour maps to show the structural requirements for potent activity. These data suggest that the amide group of B13 could be replaced by thiourea, that the stereochemistry of 1,3-propandiol may not be essential for activity and that long alkyl chains increase cytotoxicity.

Hyperplastic thyroid gland; vascular and follicular changes produced by dexamethasone during involution

The study was conducted to see the vascular and follicular changes induced by dexamethasone [synthetic corticosteroid] during involution of hyperplastic thyroid gland in albino rats. A comparative histological study done in Post Graduate Medical Institute Lahore in 1998. 54 adult rats were taken and divided at random into two control groups having 27 rats and experimental groups containing 27 rats. Control group was given normal diet along with 2 microgram of Potassium iodide intraperitonealy for 21 days while experimental groups further subdivided into group A having 3 rats and group B and C containing 12 rats each. All the experimental groups were treated with Thiourea for 21 days. Group A was sacrificed on day 22 after withdrawal of thiourea. Group B was given Potassium iodide intraperitonealy after stoppage of TU on day 21 and were sacrificed on days 22, 26, 30 and 50 in 4 sub groups [B1-B4] to study the involution process. Group C was injected dexamethasone from 22 to 50 days after withdrawal of TU and sacrificed on same days in 4 subgroups [C1-C4] as sub groups B. The results of experimental group. A showed increase in thyroid and relative tissue weight. Histologically this group exhibited significant increase in stromal congestion with tall follicular cells lining the small sized follicles having scanty colloid. The results of experimental groups B and C demonstrated increase in thyroid and relative tissue weight but microscopically subgroups B revealed early and complete involution whereas subgroups C showed significantly persistent hyperplastic changes in the form of stromal congestion, vessels wall remained well defined and tall follicular cells lining small empty follicles. It was concluded that dexamehasone did retain hyperplastic changes during involution evident by stromal congestion and small sized regular follicle lined by tall follicular cells, so it should be carefully used in thyroid diseases

Effects of clobenpropit and histidine on reinstatement of morphine-induced conditioned place preference / 浙江大学学报·医学版

<p><b>OBJECTIVE</b>To investigate the effects of clobenpropit and histidine on reinstatement of morphine-induced conditioned place preference (CPP) in rats.</p><p><b>METHODS</b>The persistence, extinction and reinstatement of morphine-induced CPP were established.In clobenpropit group three different doses of clobenpropit (2, 5 and 10 microg/rat, i.c.v.) were administered 15 min after morphine (1 mg/kg, i.p.) was injected. In histidine group histidine (100, 200, 500 mg/kg) was given 1 h prior to morphine treatment (1 mg/kg i.p).</p><p><b>RESULT</b>The CPP was reinstated by priming injection of 1 mg/kg morphine. Clobenpropit (5, 10 microg/rat) significantly inhabited the reinstatement by a priming dose of morphine-induced CPP compared with the morphine control group; histidine (100, 200, 500 mg/kg) significantly inhibited the reinstatement in a dose-dependent manner.</p><p><b>CONCLUSION</b>Clobenpropit and histidine inhibit the revival of morphine-induced CPP in a dose dependent manner, indicating that endogenous histamine may inhibit relapse of morphine to some extent.</p>

Protective effects of Peganum harmala extracts on thiourea-induced diseases in adult male rat.

Cancers and hepatoprotective prevention using traditional medicines have attracted increasing interest. The aim of our study was to characterize the putative protective effects of ethanol and chloroform extracts of Peganum harmala on thiourea-induced diseases in adult male rat. We seek to determine the effects of these plant extracts on body weight, thyroid and endocrine cancer parameters. In addition the putative hepatoprotective effect was checked by the determination of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) activities and the bilirubin level in the blood. Our data show that ethanol and chloroform extracts of Peganum harmala protected the animal against the carcinogenic effects induced by thiourea since neuron-specific enolase (NSE) and thyroglobulin (TG) levels were back to the normal range. In addition, the observed-hepatocytotoxicity after thiourea treatment was greatly reduced (AST and ALT activities were respectively 270 IU/l and 60 IU/l and in the same order of magnitude as in the untreated rats) as well as the bilirubin levels (6 micromol/l) especially for animals receiving the choroform preparation. Therefore we may suggest that extracts of Peganum harmala are efficient to reduce the toxicity induced by thiourea in male rat as far as the above parameters are concerned.

Effects of Astragalus membranaceus on atrial dynamics and ANP secretion / 中国中药杂志

<p><b>OBJECTIVE</b>To define the effects of Astragalus membranaceus on the atrial dynamics and ANP secretion in the perfused beating rabbit atria.</p><p><b>METHOD</b>The experiments have been done in isolated perfused beating rabbit atria. ANP was measured by radioimmunoassay in the atrial perfusate in real-time base.</p><p><b>RESULT</b>A. membranaceus (2.0, 2.5, 3.0 g L(-1)) could increase atria stroke volume from (694.70 +/- 0.01) microL g(-1) (P<0.05) to (1,003.00 +/- 8.80) microL g(-1) (P<0.001); (1,120.00 +/- 17.71) microL g(-1) and (1,195.00 +/- 8.21) microL g(-1) (P<0.001), respectively, and its could difference increase atrial pulse pressure from (0.82 +/- 0.01) kPa to (0.86 +/- 0.01) kPa (P<0.01); (0.96 +/- 0.01) kPa (P<0.001) and (1.02 +/- 0.01) kPa (P<0.001), respectively; A. membranaceus obviously increased rabbit atrial dynamics with dose-dependent manner. Simultaneously, A. membranaceus inhibited ANP secretion. Nifedipine (1.0 micromol L(-1)), a L-type Ca2+ channel inhibitor, and KB-R 7943 (10.0 micromol L(-1)), an inhibitor of reversed Na+ -Ca2+ exchanger, blocked the effects of A. membranaceus-induced augmentation of atrial dynamics but failed to modulation the inhibition of A. membranaceus on ANP secretion.</p><p><b>CONCLUSION</b>A. membranaceus increases the atrial dynamics via Na+ -Ca2+ exchanger and L-type Ca2+ channel and negatively modulates ANP secretion in beating rabbit atria.</p>

Conveninent synthesis and antimicrobial activity of pyrazolo [3,4-d] pyrimidine derivatives

Pyrazole derivatives 3a,b were formed upon reacting phenylhydrazine with ketene S, S-acetal or tetracyanoethylene. The pyrazole derivatives 3a, b were in turn used as precursors for the preparation of pyrazolo [3,4-d] pyrimidines which are expected to possess considerable chemical and pharmacological activities. The antimicrobial activity of the prepared compounds was tested