To evaluate the effect of proteolytic enzymes on the absorption of insulin in the buccal mucosa, the trichloroacetic acid (TCA) method was used to estimate the degradation of insulin under different conditions in the ...To evaluate the effect of proteolytic enzymes on the absorption of insulin in the buccal mucosa, the trichloroacetic acid (TCA) method was used to estimate the degradation of insulin under different conditions in the buccal mucosal homogenates. In vivo experiments estimating the enhancement of hypoglycaemic effect by enzyme inhibitors were also conducted. The results showed that proteolytic enzymes in the buccal mucosa were less active than in the intestine. Bacitracin, aprotinin and sodium deoxycholate could inhibit the degradation of insulin in the buccal mucosal homogenates. The degradation of insulin in buccal mucosal homogenates of normal hamsters was smaller than that of diabetic hamsters. In vivo experiments of hypoglycaemia supported the in vitro results. When given buccally, bacitracin, aprotinin and sodium deoxycholate could increase the relative pharmacological bioavailability of insulin. When co-administered with aprotinin(0.1%), bacitracin(0.5%) and sodium deoxycholate(5%), the relative pharmacological bioavailabilities of insulin were 4.84%, 6.60% and 14.95% respectively. The in vitro and in vivo results suggest that proteolytic enzymes are present in the buccal mucosa, which limit absorption of insulin. Co-administration with some enzyme inhibitors can improve the bioavailability of insulin via buccal delivery and sodium deoxycholte is more efficient than some enzyme inhibitors used for improving buccal absorption.展开更多
Irritable bowel syndrome (IBS) is a functional gut disorder with high prevalence.Because of various factors involved in its pathophysiology and disappointing results from conventional IBS medications,the treatment of ...Irritable bowel syndrome (IBS) is a functional gut disorder with high prevalence.Because of various factors involved in its pathophysiology and disappointing results from conventional IBS medications,the treatment of IBS is challenging and use of complementary and alternative medicines especially herbal therapies is increasing.In this paper,electronic databases including PubMed,Scopus,and Cochrane library were searched to obtain any in vitro,in vivo or human studies evaluating single or compound herbal preparations in the management of IBS.One in vitro,3 in vivo and 23 human studies were included and systematically reviewed.The majority of studies are about essential oil of Menta piperita as a single preparation and STW 5 as a compound preparation.Some evaluated herbs such as Curcuma xanthorriza and Fumaria officinalis did not demonstrate any benefits in IBS.However,it seems there are many other herbal preparations such as those proposed in traditional medicine of different countries that could be studied and investigated for their efficacy in management of IBS.展开更多
AIM： To investigate in vitro and in vivo therapeutic effects of histone deacetylase inhibitors NVP-LAQ824 and NVP-LBH589 on biliary tract cancer. METHODS： Cell growth inhibition by NVP-LAQ824 and NVP-LBH589 was stud...AIM： To investigate in vitro and in vivo therapeutic effects of histone deacetylase inhibitors NVP-LAQ824 and NVP-LBH589 on biliary tract cancer. METHODS： Cell growth inhibition by NVP-LAQ824 and NVP-LBH589 was studied in vitro in 7 human biliary tract cancer cell lines by MTT assay. In addition, the antitumoral effect of NVP-LBH589 was studied in a chimeric mouse model. Anti-tumoral drug mechanism was assessed by immunoblotting for acH4 and p21^WAFl/CIP-1, PARP assay, cell cycle analysis, TUNEL assay, and immunhistochemistry for MIB-1. RESULTS： In vitro treatment with both compounds significantly suppressed the growth of all cancer cell lines [mean IC50 （3 d） 0.11 and 0.05 μmol/L, respectively], and was associated with hyperacetylation of nucleosomal histone H4, increased expression of p21^WAF-1/CIP-1, induction of apoptosis （PARP cleavage）, and cell cycle arrest at G2/M checkpoint. After 28 d, NVP- LBH589 significantly reduced tumor mass by 66% （bile duct cancer） and 87% （gallbladder cancer） in vivo in comparison to placebo, and potentiated the efficacy of gemcitabine. Further analysis of the tumor specimens revealed increased apoptosis by TUNEL assay and reduced cell proliferation （MIB-1）. CONCLUSION： Our findings suggest that NVP-LBH589 and NVP-LAQ824 are active against human biliary tract cancer in vitro. In addition, NVP-LBH589 demonstrated significant in vivo activity and potentiated the efficacy of gemcitabine. Therefore, further clinical evaluation of this new drug for the treatment of biliary tract cancer is recommended.展开更多
Objective： To observe the therapeutic effect of medicine-separated moxibustion for primary dysmenorrhea and its influence on plasma hormone level. Methods. Ninety-six patients suffering from primary dysmenorrhea were...Objective： To observe the therapeutic effect of medicine-separated moxibustion for primary dysmenorrhea and its influence on plasma hormone level. Methods. Ninety-six patients suffering from primary dysmenorrhea were randomly and evenly divided into trealment group treated with medicine-separated moxibustion of Shenque （神阙 CV 8, 3-5 cones every time, beginning 1 week before onset of menstruation and stopping on the 3^rd day after onset, with 10 sessions being a therapeutic oourse, 3 courses all together）, and control group treated with oral administration of Yueyueshu （月月舒 menstruation-smoothing granule, 10 g/time, b.i.d, 3 courses altogether）. Menses prostaglandin E2（PGF2α） and plasma oxytocin （OT） during menstruation were determined by radioimmunoassay. Results; After the treatment, of the two 48 cases in treatment and control groups, 18 and 5 were cured, 24 and 9 had marked improvement in their symptoms, 6 and 26 had improvement, 0 and 8 failed in the treatment, with the total effective rates being 100. 096 and 83.3% respectively, the therapeutic effect of treatment group was markedly superior to that of control group （P〈0.05）. After the treatment, the contents of menses PGF2α in treatment group and plasma OT in both groups were significantly lower than those of pre-treatment （ P〈 0.01 ）. The therapeutic effect of moxibustion was significant- ly better than that of medication in lowering plasma OT. Conclusion： Medicine-separated moxibustion works well in treating primary dysmenorrhea, and moxibustion induced decrease of menses PGF2α and plasma OT may contribute to its effect in relieving dysmenorrhea.展开更多
This article reviews the pathogenic mechanism of nonsteroidal anti-inflammatory drug(NSAID)-induced gastric damage,focusing on the relation between cyclooxygenase(COX) inhibition and various functional events.NSAIDs,s...This article reviews the pathogenic mechanism of nonsteroidal anti-inflammatory drug(NSAID)-induced gastric damage,focusing on the relation between cyclooxygenase(COX) inhibition and various functional events.NSAIDs,such as indomethacin,at a dose that inhibits prostaglandin(PG) production,enhance gastric motility,resulting in an increase in mucosal permeability,neutrophil infiltration and oxyradical production,and eventually producing gastric lesions.These lesions are prevented by pretreatment with PGE 2 and antisecretory drugs,and also via an atropine-sensitive mechanism,not related to antisecretory action.Although neither rofecoxib(a selective COX-2 inhibitor) nor SC-560(a selective COX-1 inhibitor) alone damages the stomach,the combined administration of these drugs provokes gastric lesions.SC-560,but not rofecoxib,decreases prostaglandin E 2(PGE 2) production and causes gastric hypermotility and an increase in mucosal permeability.COX-2 mRNA is expressed in the stomach after administration of indomethacin and SC-560 but not rofecoxib.The up-regulation of indomethacin-induced COX-2 expression is prevented by atropine at a dose that inhibits gastric hypermotility.In addition,selective COX-2 inhibitors have deleterious influences on the stomach when COX-2 is overexpressed under various conditions,including adrenalectomy,arthritis,and Helicobacter pylori-infection.In summary,gastric hypermotility plays a primary role in the pathogenesis of NSAID-induced gastric damage,and the response,causally related with PG deficiency due to COX-1 inhibition,occurs prior to other pathogenic events such as increased mucosal permeability;and the ulcerogenic properties of NSAIDs require the inhibition of both COX-1 and COX-2,the inhibition of COX-1 upregulates COX-2 expression in association with gastric hypermotility,and PGs produced by COX-2 counteract the deleterious effect of COX-1 inhibition.展开更多
It is challenging for many drugs to be transported across various biological membranes. Furthermore, development of many drugs gets thwarted owing to their hydrophilic nature. The bioavailability of such drugs, which ...It is challenging for many drugs to be transported across various biological membranes. Furthermore, development of many drugs gets thwarted owing to their hydrophilic nature. The bioavailability of such drugs, which is the function of their ability to cross the membrane, tends to be low and exhibit high intra and inter subject variability. At present, formulation scientists are pursuing many projects for transdermal, nasal, target delivery of many active compounds, and it is prudent to explore alternative possibilities. Cubosomes offer transportation and tailoring of active compounds intended for both systemic and dermal delivery. Cubosomes are dispersed, self-assembled nanoparticles of bicontinuous cubic liquid crystalline phase formed from lipid and surfactant systems. Monoolein, poloxamer 407 and polyvinyl alcohol are the mostly used ingredients in the formulation of cubosomes. The adjustment in lipid composition can control the internal and structural changes of cubosomes. Based on the nodal surfaces, three structures of cubosomes proposed are Pn3m, Ia3d and Im3m. Top-down and bottom-up techniques are widely considered in the formulation process of extreme viscous bulk phase and aggregate from a precursor respectively. This article gives a bird's eye view about the engineering, characterization and evaluation of cubosomes, covering researches and applications of cubosomes done till date.展开更多
文摘To evaluate the effect of proteolytic enzymes on the absorption of insulin in the buccal mucosa, the trichloroacetic acid (TCA) method was used to estimate the degradation of insulin under different conditions in the buccal mucosal homogenates. In vivo experiments estimating the enhancement of hypoglycaemic effect by enzyme inhibitors were also conducted. The results showed that proteolytic enzymes in the buccal mucosa were less active than in the intestine. Bacitracin, aprotinin and sodium deoxycholate could inhibit the degradation of insulin in the buccal mucosal homogenates. The degradation of insulin in buccal mucosal homogenates of normal hamsters was smaller than that of diabetic hamsters. In vivo experiments of hypoglycaemia supported the in vitro results. When given buccally, bacitracin, aprotinin and sodium deoxycholate could increase the relative pharmacological bioavailability of insulin. When co-administered with aprotinin(0.1%), bacitracin(0.5%) and sodium deoxycholate(5%), the relative pharmacological bioavailabilities of insulin were 4.84%, 6.60% and 14.95% respectively. The in vitro and in vivo results suggest that proteolytic enzymes are present in the buccal mucosa, which limit absorption of insulin. Co-administration with some enzyme inhibitors can improve the bioavailability of insulin via buccal delivery and sodium deoxycholte is more efficient than some enzyme inhibitors used for improving buccal absorption.
文摘Irritable bowel syndrome (IBS) is a functional gut disorder with high prevalence.Because of various factors involved in its pathophysiology and disappointing results from conventional IBS medications,the treatment of IBS is challenging and use of complementary and alternative medicines especially herbal therapies is increasing.In this paper,electronic databases including PubMed,Scopus,and Cochrane library were searched to obtain any in vitro,in vivo or human studies evaluating single or compound herbal preparations in the management of IBS.One in vitro,3 in vivo and 23 human studies were included and systematically reviewed.The majority of studies are about essential oil of Menta piperita as a single preparation and STW 5 as a compound preparation.Some evaluated herbs such as Curcuma xanthorriza and Fumaria officinalis did not demonstrate any benefits in IBS.However,it seems there are many other herbal preparations such as those proposed in traditional medicine of different countries that could be studied and investigated for their efficacy in management of IBS.
文摘AIM： To investigate in vitro and in vivo therapeutic effects of histone deacetylase inhibitors NVP-LAQ824 and NVP-LBH589 on biliary tract cancer. METHODS： Cell growth inhibition by NVP-LAQ824 and NVP-LBH589 was studied in vitro in 7 human biliary tract cancer cell lines by MTT assay. In addition, the antitumoral effect of NVP-LBH589 was studied in a chimeric mouse model. Anti-tumoral drug mechanism was assessed by immunoblotting for acH4 and p21^WAFl/CIP-1, PARP assay, cell cycle analysis, TUNEL assay, and immunhistochemistry for MIB-1. RESULTS： In vitro treatment with both compounds significantly suppressed the growth of all cancer cell lines [mean IC50 （3 d） 0.11 and 0.05 μmol/L, respectively], and was associated with hyperacetylation of nucleosomal histone H4, increased expression of p21^WAF-1/CIP-1, induction of apoptosis （PARP cleavage）, and cell cycle arrest at G2/M checkpoint. After 28 d, NVP- LBH589 significantly reduced tumor mass by 66% （bile duct cancer） and 87% （gallbladder cancer） in vivo in comparison to placebo, and potentiated the efficacy of gemcitabine. Further analysis of the tumor specimens revealed increased apoptosis by TUNEL assay and reduced cell proliferation （MIB-1）. CONCLUSION： Our findings suggest that NVP-LBH589 and NVP-LAQ824 are active against human biliary tract cancer in vitro. In addition, NVP-LBH589 demonstrated significant in vivo activity and potentiated the efficacy of gemcitabine. Therefore, further clinical evaluation of this new drug for the treatment of biliary tract cancer is recommended.
文摘Objective： To observe the therapeutic effect of medicine-separated moxibustion for primary dysmenorrhea and its influence on plasma hormone level. Methods. Ninety-six patients suffering from primary dysmenorrhea were randomly and evenly divided into trealment group treated with medicine-separated moxibustion of Shenque （神阙 CV 8, 3-5 cones every time, beginning 1 week before onset of menstruation and stopping on the 3^rd day after onset, with 10 sessions being a therapeutic oourse, 3 courses all together）, and control group treated with oral administration of Yueyueshu （月月舒 menstruation-smoothing granule, 10 g/time, b.i.d, 3 courses altogether）. Menses prostaglandin E2（PGF2α） and plasma oxytocin （OT） during menstruation were determined by radioimmunoassay. Results; After the treatment, of the two 48 cases in treatment and control groups, 18 and 5 were cured, 24 and 9 had marked improvement in their symptoms, 6 and 26 had improvement, 0 and 8 failed in the treatment, with the total effective rates being 100. 096 and 83.3% respectively, the therapeutic effect of treatment group was markedly superior to that of control group （P〈0.05）. After the treatment, the contents of menses PGF2α in treatment group and plasma OT in both groups were significantly lower than those of pre-treatment （ P〈 0.01 ）. The therapeutic effect of moxibustion was significant- ly better than that of medication in lowering plasma OT. Conclusion： Medicine-separated moxibustion works well in treating primary dysmenorrhea, and moxibustion induced decrease of menses PGF2α and plasma OT may contribute to its effect in relieving dysmenorrhea.
文摘This article reviews the pathogenic mechanism of nonsteroidal anti-inflammatory drug(NSAID)-induced gastric damage,focusing on the relation between cyclooxygenase(COX) inhibition and various functional events.NSAIDs,such as indomethacin,at a dose that inhibits prostaglandin(PG) production,enhance gastric motility,resulting in an increase in mucosal permeability,neutrophil infiltration and oxyradical production,and eventually producing gastric lesions.These lesions are prevented by pretreatment with PGE 2 and antisecretory drugs,and also via an atropine-sensitive mechanism,not related to antisecretory action.Although neither rofecoxib(a selective COX-2 inhibitor) nor SC-560(a selective COX-1 inhibitor) alone damages the stomach,the combined administration of these drugs provokes gastric lesions.SC-560,but not rofecoxib,decreases prostaglandin E 2(PGE 2) production and causes gastric hypermotility and an increase in mucosal permeability.COX-2 mRNA is expressed in the stomach after administration of indomethacin and SC-560 but not rofecoxib.The up-regulation of indomethacin-induced COX-2 expression is prevented by atropine at a dose that inhibits gastric hypermotility.In addition,selective COX-2 inhibitors have deleterious influences on the stomach when COX-2 is overexpressed under various conditions,including adrenalectomy,arthritis,and Helicobacter pylori-infection.In summary,gastric hypermotility plays a primary role in the pathogenesis of NSAID-induced gastric damage,and the response,causally related with PG deficiency due to COX-1 inhibition,occurs prior to other pathogenic events such as increased mucosal permeability;and the ulcerogenic properties of NSAIDs require the inhibition of both COX-1 and COX-2,the inhibition of COX-1 upregulates COX-2 expression in association with gastric hypermotility,and PGs produced by COX-2 counteract the deleterious effect of COX-1 inhibition.
文摘It is challenging for many drugs to be transported across various biological membranes. Furthermore, development of many drugs gets thwarted owing to their hydrophilic nature. The bioavailability of such drugs, which is the function of their ability to cross the membrane, tends to be low and exhibit high intra and inter subject variability. At present, formulation scientists are pursuing many projects for transdermal, nasal, target delivery of many active compounds, and it is prudent to explore alternative possibilities. Cubosomes offer transportation and tailoring of active compounds intended for both systemic and dermal delivery. Cubosomes are dispersed, self-assembled nanoparticles of bicontinuous cubic liquid crystalline phase formed from lipid and surfactant systems. Monoolein, poloxamer 407 and polyvinyl alcohol are the mostly used ingredients in the formulation of cubosomes. The adjustment in lipid composition can control the internal and structural changes of cubosomes. Based on the nodal surfaces, three structures of cubosomes proposed are Pn3m, Ia3d and Im3m. Top-down and bottom-up techniques are widely considered in the formulation process of extreme viscous bulk phase and aggregate from a precursor respectively. This article gives a bird's eye view about the engineering, characterization and evaluation of cubosomes, covering researches and applications of cubosomes done till date.
