碱性去活柱反相高效液相色谱法分析红霉素肟及相关化合物

采用碱性去活（BDS）C18柱分离测定了红霉素肟及相关化合物。以0．02mol／L磷酸氢二钾（用磷酸调pH7．2）-乙腈-甲醇（体积比为50：40：10）为流动相，检测波长为210nm，柱温为35℃。红霉素肟E、Z异构体及相关化合物红霉素A、红霉素A8，9-脱水-6，9-半缩酮和红霉素A6，9-9，12-螺缩酮五种组分分离完全，检测限（S/N=3）为6．0～24．0ng，线性关系良好，方法准确可靠，用于实际样品分析时取得较好的效果。

Synthesis and Antibacterial Activities of Erythromycin Derivatives

Aim To synthesize 4″-carbamate derivatives of erythromycin and test their antibacterial activities in vitro. Methods New erythromycin antibacterial agents containing 4″-carbamate group were designed and synthesized from azithromycin via protection, aminoformylation, amination and deprotection. Their antibacterial activities against Staphylococcus aureus strains were tested. Results Nine compounds were synthesized. Their structures were confirmed by MS, IR, ~ 1 H NMR and ~ 13 C NMR, and the synthetic conditi...

Expression of motilin in the hypothalamus and the effect of central eryth-romycin on gastric motility in diabetic rats

Objective To investigate the expression of motilin-immunoreactive neurons in the hypothalamus and the effect of central administration of erythromycin （EM） on the regulation of gastric motility in diabetic rats. Methods The motilin immunoreactive neurons in the hypothalamus and the hippocampus were detected by immunohistochemistry with rabbit anti-motilin polyclonal antibody. To measure the gastric motility, force transducers were surgically affixed to the gastric serosa. A microinjection syringe was connected via a plastic tube to an injection cannula, which was connected with a stainless steel guide cannula. The syringe was inserted into the right lateral cerebral ventricle for microinjecting the chemicals. Results Diabetic mellitus was successfully induced in cohorts of rats. Motilin-immunoreactive neurons significantly increased in the paraventricular （PVN） and supraoptic nuclei （SON） of the hypothalamus in the diabetic rats. Intracerebroventricular （i.c.v.） administration of EM, a motilin receptor agonist, stimulated the gastric motility of diabetic rats. EM （91.56 nmol, i.c.v.） dose-dependently increased the amplitude by （174.82±48.62）% （P 〈 0.05）, and increased the frequency by （70.43±27.11）% （P 〈 0.05） in 5 min. The stimulatory effect lasted more than 15 min to the end of the measurement, and can be blocked partially by the prior treatment of motilin receptor antagonist GM-109. Conclusion Motilin-immunoreactive neurons are increased in the PVN and SON of the hypothalamus in diabetic rats. Centrally administered EM may regulate gastric motility by binding to the central motilin receptors, and central motilin might be involved in regulation of gastric motility in diabetic rats.

Capsule endoscopy: Improving transit time and image view

AIM： To evaluate the effect of various methods of small bowel preparation on the transit time and the quality of visualization of the entire small bowel mucosa. METHODS： Ninety-five patients underwent capsule endoscopy （CE） by easily swallowing the capsule. They were divided into three study groups according to the preparation used： group A （n = 26） by polyethylene glycol （PEG） liter or with sodium phosphate （SP） 12 h prior to the CE study; group B （n = 29） by erythromycin 1 h prior to the CE study; and group C （n = 40） without any preparation. Visualization ranged from good to satisfactory to poor. RESULTS： The gastric emptying time in the group prepared with erythromycin was shorter but without statistical significance and the small bowel transit time was unaffected. In elderly subjects prepared by PEG or SP, the gastric emptying time was significantly longer （163.7 rain, P = 0.05）. The transit times of the three sub-groups were not affected by gender or pathology. The grade of cleaning of the entire study group was 3.27±1.1. The erythromycin group presented significantly the worst quality of images （P = 0.05） compared to the other sub-groups. Age, gender, and pathology had no effect on the quality of the cleaning of the small bowel in the sub-groups. One （1.05%） case had no natural excretion. CONCLUSION： Erythromycin markedly reduces gastric emptying time, but has a negative effect on the quality of the image in the small bowel. The preparation of elderly subjects with PEG or SP has a negative effect on the small bowel transit time.

Mechanisms underlying feed intolerance in the critically ill: Implications for treatment

Malnutrition is associated with poor outcomes in critically ill patients. Although nutritional support is yet to be proven to improve mortality in non-malnourished critically ill patients, early enteral feeding is considered best practice. However, enteral feeding is often limited by delayed gastric emptying. The best method to clinically identify delayed gastric emptying and feed intolerance is unclear. Gastric residual volume （GRV） measured at the bedside is widely used as a surrogate marker for gastric emptying, but the value of GRV measurement has recently been disputed. While the mechanisms underlying delayed gastric emptying require further investigation, recent research has given a better appreciation of the pathophysiology. A number of pharmacological strategies are available to improve the success of feeding. Recent data suggest a combination of intravenous metoclopramide and en/thromycin to be the most successful treatment, but novel drug therapies should be explored. Simpler methods to access the duodenum and more distal small bowel for feed delivery are also under investigation. This review summarises current understanding of the factors responsible for, and mechanisms underlying feed intolerance in critical illness, together with the evidence for current practices. Areas requiring further research are also highlighted.

Effect of oral erythromycin on gastric and small bowel transit time of capsule endoscopy

AIM： To determine the effect of oral erythromycin on gastric and small bowel transit time of capsule endoscopy. METHODS： Consecutive patients who underwent capsule endoscopy during the 16-mo study period were either given 250 mg oral erythromycin, 1 h prior to swallowing the capsule endoscope or nothing. The gastric and small bowel transit time, and the small bowel image quality were compared. RESULTS： Twenty-four patients received oral erythromycin whereas 14 patients were not given any prokinetic agent. Patients who received erythromycin had a significantly lower gastric transit time than control （16 min vs70 min, P= 0.005）, whereas the small bowel transit time was comparable between the two groups （227 rain vs 183 min, P= 0.18）. Incomplete small bowel examination was found in three patients of the control group and in one patient of the erythromycin group. There was no significant difference in the overall quality of small bowel images between the two groups. A marked reduction in gastric transit time was noted in two patients who had repeat capsule endoscopy after oral erythromycin. CONCLUSION： Use of oral erythromycin significantly reduces the gastric transit time of capsule endoscopy.

Effect of erythromycin on image quality and transit time of capsule endoscopy: A two-center study

AIM: To compare the effect of oral erythromycin vs no preparation with prokinetics on the transit time and the image quality of capsule endoscopy (CE) in evaluating small bowel (SB) pathology. METHODS: We conducted a retrospective, blinded (to the type of preparation) review of 100 CE studies, 50 with no preparation with prokinetics from one medical center (Group A) and 50 from another center with administration of a single dose of 200 mg oral erythromycin 1 h prior to CE (Group B). Gastric, SB and total transit times were calculated, the presence of bile in the duodenum was scored, as was cleanliness within the proximal, middle and distal intestine. RESULTS: The erythromycin group had a slightly shorter gastric transit time (21 min vs 28 min, with no statistical significance). SB transit time was similar for both groups (all P > 0.05). Total transit time was almost identical in both groups. The rate of incomplete examination was 16% for Group A and 10% for Group B (P = 0.37). Bile and cleanliness scores in different parts of the intestine were similar for the two groups (P > 0.05). CONCLUSION: Preparation for capsule endoscopy with erythromycin does not affect SB or total transit time. It tends to reduce gastric transit time, but it does not increase the cecum-reaching rate. Erythromycin does not adversely affect image quality. We consider the routine use of oral erythromycin preparation as being unjustified, although it might be considered in patients with known prolonged gastric emptying time.

Metabolism of Praziquantel in Erythromycin, Acetylspi-ramycin and Dexamethasone Induced Rat Liver Micro-somes

Our results show that in liver microsomes from erythromycin,acetylspiramycin and dexamethsone pretreated rats,the rate of praziquantel( PQT)disappearence was increased as compared with control rat When microsomes from erythromycin-treated rats were exposed to PQT in the presence of potassium ferricyanide which broke down the cytochrome P-450 Fe(Ⅱ)-metabolite complexes and restored the functional cytochrome P-450,PQT metabolism was further increased. Acetylspiramycin did not form the complexes, so potassium ferricyanide showed no effect on the PQT metabolism in microsomes from acetylspiramycin-treated rats. Triacetyloleandomycin,a specific inhibitor of cytochrome P-450ⅢAI, inhibited PQT metabolism by 53% in liver microsomes from dexamethasone-treated rats.These results indicate the cytochrome P-450ⅢA seems to be involved in metabolism of PQT in rat liver microsomes.

Relative efficacy of some prokinetic drugs in morphine-induced gastrointestinal transit delay in mice

AIM:To study the relative efficacy of cisapride, metoclopramide,domperidone,erythromycin and mosapride on gastric emptying(GE)and small intestinal transit(SIT) in morphine treated mice. METHODS:Phenol red marker meal was employed to estimate GE and SIT in Swiss albino mice of either sex.The groups included were control,morphine 1 mg/kg(s.c.15 rain before test meal)alone or with(45 rain before test meal p.o.)cisapride 10 mg/kg,metoclopramide 20 mg/kg, domperidone 20 mg/kg,erythromycin 6 mg/kg and mosapride 20 mg/kg. RESULTS:Cisapride,metoclopramide and mosapride were effective in enhancing gastric emptying significantly(P<0.001) whereas other prokinetic agents failed to do so in normal mice.Metoclopramide completely reversed morphine induced delay in gastric emptying followed by mosapride. Metoclopramide alone was effective when given to normal mice in increasing the SIT.Cisapride,though it did not show any significant effect on SIT in normal mice,was able to reverse morphine induced delay in SIT significantly(P<0.001) followed by metoclopramide and mosapride. CONCLUSION:Metoclopramide and cisapride are most effective in reversing morphine-induced delay in gastric emptying and small intestinal transit in mice respectively.

EFFECT OF ERYTHROMYCIN ON GASTRIC DYSMOTILITY AND NEUROENDOCRINE PEPTIDES IN RATS WITH DIABETES MELLITUS

Objective To investigate the effect of erythromycin on the contractive activity of the isolated gastric antrum smooth muscle and somatostatin （SS）, vasoactive intestinal peptide （VIP）, motilin （MTL）, and substance P （SP） in plasma and isolated gastric antrum tissue of diabetes mellitus （DM） rat models. Methods Thirty male Sprague-Dawley rats were divided into three groups： control group （n = 10）, DM group （n = 10）, and erythromycin group （DM models with erythromycin treatment, n = 10）. A single dose of streptozotocin （100 mg/kg, dissolved in 0. I mol/L citric acid buffer, pH4.5） was injected intraperitoneally. After 48 to 72 hours, rats with blood glucose above 16.7 mmol/L and urine glucose level to be （＋＋＋ ） to （＋＋＋＋） over one week were considered successful DM models. The resting tension, mean contractile amplitude and fi＇equency of spontaneous change in isolated longitudinal and circular gastric antrum smooth muscle strips were measured. SS, VIP, MTL, and SP levels in plasma and gastric antrum tissue were measured using radioimmunoassay. Results （1） In the isolated gastric antrum smooth muscle strips, the gastric motility parameters were lower in DM group than those in control group except circular smooth muscle contractile amplitude and longitudinal smooth muscle contractile fi＇equency. The gastric motility parameters were significantly strengthened in erythromycin group, compared with DM group except longitudinal smooth muscle resting tension （P 〈 0.01 ）. （2） Plasma SS, VIP, and MTL concentrations in DM group were higher than those in control （P 〈 0.05）, while the SP level decreased （P 〈 0.05）. In the gastric antrum, SS of DM group was significantly higher than that of control group （P 〈 0.01 ）, while SP and MTL levels were lower than those of control group （P 〈 0.05 and P 〈 0.01, respectively）. However, the level of VIP in gastric antrum tissue did not change among three groups. The plasma level of SS in erythromycin group was higher than that of DM group （P 〈 0.05）. （3） The blood glucose was lower in erythromycin group than DM group （P 〈 0.01 ）. Conclusions Erythromycin has direct effects on contractive activity of gastric smooth muscle in diabetic rats, but there are few effects on neuroendocrine peptides. Gastric-motility disorders in diabetic rats have a correlation with the changes of neuroendocrine peptide levels in plasma and gastric antrum tissue.

Myasthenia gravis exacerbation and diarrhea associated with erythromycin treatment

An important problem in management of the case with myasthenia gravis (MG) is the control of exacerbation. There are several possible causes of exacerbation of MG including the use of drug. Here, the authors report a case of MG exacerbation and diarrhea associated with erythromycin treatment.

Molecular Epidemiological Analysis of Group A Streptococci Isolated from Children in Chaoyang District of Beijing, 2011:emm Types, Virulence Factor Genes and Erythromycin Resistant Genes

Group A streptococcus （GAS） causes a wide range of diseases in the human population. GAS diseases are more common in children than in adults, with clinical manifestations ranging from pharyngitis and impetigo to invasive infections and post streptococcal sequelae, such as acute rheumatic fever and acute post-streptococcal glomerulonephritis[1]. GAS harbors a host of virulence factors that contribute to its complex pathogenicity and differences in the disease severity and frequency. M protein, one of the major virulence factors, is encoded by the emm gene induces a type of specific host immune response and confers antiphagocytic properties.

Efficacy of different antibiotics in treatment of children with respiratory mycoplasma infection

BACKGROUND Respiratory infections in children are common pediatric diseases caused by pathogens that invade the respiratory system.Children are considerably susceptible to Mycoplasma pneumoniae infection.There has been widespread clinical attention on treatment strategies for this disease.AIM To analyze the clinical efficacy of different antibiotics in treating pediatric respiratory mycoplasma infections.METHODS We included 106 children with a confirmed diagnosis of respiratory mycoplasma infection who were admitted to our hospital from April 2017 to July 2019 and grouped them using a random number table.Among them,53 children each received clarithromycin or erythromycin.The clinical efficacy of both drugs was evaluated and compared.We performed the multiplex polymerase chain reaction(MP-PCR)test and determined the MP-PCR negative rate in children after the end of the treatment course.We compared the incidence of toxic and side effects,including nausea,diarrhea,and abdominal pain;further,we recorded the length of hospitalization,antipyretic time,and drug costs.Additionally,we evaluated and compared the compliance of the children during treatment.RESULTS The erythromycin group showed a significantly higher total effective rate of clinical treatment than the clarithromycin group.MP-PCR test results showed that the clarithromycin group had a significantly higher MP-PCR negative rate than the erythromycin group.Moreover,children in the clarithromycin group had shorter fever time,shorter hospital stays,and lower drug costs than those in the erythromycin group.The clarithromycin group had a significantly higher overall drug adherence rate than the erythromycin group.The incidence of toxic and side effects was significantly lower in the clarithromycin group than in the erythromycin group(P<0.05).CONCLUSION Our findings indicate that clarithromycin has various advantages over erythromycin,including higher application safety,stronger mycoplasma clearance,and higher medication compliance in children;therefore,it can be actively promoted.

A report on infection dynamics of inducible clindamycin resistance of Staphylococcus aureus isolated from a teaching hospital in India

Objective:To investigate the infection of hospital-and community-acquired"erythromycininduced clindamycin resistant"strains or D-test positives of clinical isolates of Staphylococcus aureus(S.aureus)(with and without methicillin resistance)in a hospital.Methods:Strains of S.aureus isolated from clinical specimens were subjected to D-test and antibiotic profiling.Results:Of the total 278 isolates,140(50.35%)were D-test positives and the rest were D-test negatives.Further,of 140(100%)pesitives,87(62.14%)and 53(37.85%)strains were from males and females,respectively.Of 140(100%)pesitives,117(83.57%)were methicillin resistant S.aureus and23(16.42%)were methicillin sensitive S.aureus;of 140 strains,103(73.57%)strains front persons with and 37(26.42%)were without related infections;of 140 strains,91(65%)and 49(35%)were from hospital-and community-acquired samples,respectively.In 140 strains,118(84.28%)with comorbidities and 22(15.71%)without comorbidities cases were recorded;similarly,persons with prior antibiotic uses contributed 108(77.14%)and without 32(22.85%)positive strains.These binary data of surveillance were analyzed by a univariate analysis.It was evident that the prior antibiotic uses and comorbidities due to other ailments were the determinative factors in D-test positivity,corroborated by low P values,P=0.001 1 and 0.0024,respectively.All isolates(278)were resistant to17 antibiotics of nine groups,in varying degrees;the minimum of 28%resistance for vancomycin and the maximum of 97%resistance for gentamicin were recorded.Further,of 278 strains,only42(15.1%)strains were resistant constitutively to both antibiotics,erythromycin resistant and clindamycin resistant,while 45(16.2%)strains were constitutively sensitive to both antibiotics(erythromycin sensitive,and clindamycin sensitive).Further,of the rest 191(68.7%)strains were with erythromycin resistant and clindamycin resistant,of which only 140(50.35%)strains were D-test positives,while the rest 51(18.34%)strains were D-test negatives.Conclusions:In view of high prevalence of D-test positive S.aureus strains,and equally high prevalence of multidrug resistant strains both in community and hospital sectors,undertaking of D-test may be routinely conducted for suppurative infections.

Preparation, Characterization, and in vitro Release of Biodegradable Erythromycin-gelatin Microspheres

Blank and erythromycin-loaded gelatin microspheres were successfully fabricated via emulsion chemical- crosslinking technique. The surface morphology of the microspheres was characterized by scanning electron microscope（SEM） and optical microscope. The results show that the microspheres were spherical and smooth. The particle average size of erythromycin-loaded microspheres was found to be 20.6 μm, with a high purity of more than 90% and with a good dispersibility. The microspheres could be obtained in a high yield. Erythromycin released from the microspheres was monitored in buffer and artificial body fluid at 37 ℃. Average drug content was 27.2%, and erythromycin-loaded gelatin microspheres showed good release profiles with a nearly constant release during 4-8 h in artificial body fluid in vitro degradation studies. These gelatin microspheres are useful for studying and developing various drug-delivery systems.

Beckmann Rearrangement of Erythromycin A 9(E)-Oxime

Deoxo 6 deoxy 6,9 epoxy 9,9 a didehydro 9 a aza 9 a homoerythromycin A (1), 9 deoxo 11 deoxy 9,11 epoxy 9,9 a didehydro 9 a aza 9 a homoerythromycin A (2) and 9 a aza 9 a homoerythromycin cyclic lactam (3) were synthesized by the Beckmann rearrangement of erythromycin A 9 (E) oxime (4). The structures of compounds (1), (2) and (3) have been identified by their spectral data. The reaction mechanism was also discussed. The yield of the Beckmann rearrangement of compounds (4) was better than that reported in literatures.

Chiral Separation of Erythromycin as a New Chiral Selector on CE

Erythromycin as a new chiral selector was first used for chrial separation of four derivatives of biphenyldimethylester enantiomers on CE. The influence of pH, the chiral selector concentration and organic modifiers were preliminarily studied. Experiments show that the erythromycin as chiral selector is useful to CE.

Neutral Complex Extraction and Synergistic Extraction of Macrolide Antibiotics

Based on the theory of reactive extraction, new solvent systems were developed to replace butylacetate for extraction of macrolide antibiotics (erythromycin, kitasamycin, spiramycin meleumycin etc.). A new neutral complex solvent extraction system, fatty alcohol-kerosene (marked by El), was used for extraction of erythromycin, one of the macrolide antibiotics. The extraction equilibrium equation is obtained, and the extraction distribution is as followsD = exp (-36.33×103/RT + 18.77)[B](o)1.1/(1 + 108.07-PH)The effects of several parameters on extraction equilibrium were investigated. Furthermore, a new synergistic extraction system (marked by E2) was developed, in which another solvent was used as synergistic agent to replace the diluent kerosene in the neutral complex extraction system. Based on these new extraction systems, an improved process for extraction of erythromycin was developed, showing remarkable advantages in technology and economics owing to its low solvent consumption of 3kg per billion unit compared with 9—10 for butylacetate. The recovery process of solvent from raffinate may be eliminated.

Synthesis and Antibacterial Activities of Erythromycin Derivatives

Ten new erythromycin antibacterial agents containing amidino group were designed and synthesized from erythromycin via oximation, reduction and condensation. Their structures were confirmed by MS and 13C NMR; the synthetic condition(reaction medium)was explored; and their in vtiro antibacterial activities were tested. Compound HMA-3 showed antibacterial activity against staphylococcus aureus, which is equivalent to that of erythromycin A. Compounds HMA-8 and HMA-4 also showed an antibacterial activitiy. But no compound showed bactericidal activity.

Effects of erythromycin on pressure in pyloric antrum and plasma motilin and somatostatin content in dogs

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