[Skin needle embedding for obese impaired glucose tolerance].

OBJECTIVE: To explore the effect difference between the skin needle embedding therapy and western medication for obese impaired glucose tolerance (IGT). METHODS: A total of 300 cases of obese IGT were assigned into an embedding group and a western medication group by random number table, 150 cases in each one. Standardized diagnosis and treatment programs were applied to reduce blood pressure, lipid, weight, and exercise and scientific diet management were used. 0.25 g oral deltamine was prescribed three times a day in the western medication group. Thumb-tack needle for subcutaneous embedding was at bilateral Weiwanxiashu (EX-B 3), Ganshu (BL 18), Pishu (BL 20), Tianshu (ST 25) and Zusanli (ST 36) for 36 to 48 hours on Monday and Thursday, 3 months as a session, with other acupoints differentiated. All the treatment was given for 2 years. The indexes included the blood sugar indexes [fasting plasma glucose (FPG), 2 h postprandial blood glucose (2 h PG), glycosylated hemoglobin (HbA1c)], incidence of hypoglycemia, obesity indexes [waist circumference, body mass index (BMI)], blood lipid indexes [serum total cholesterol (TC), serum triacylglycerol (TG), low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C)], liver and kidney function indexes [serum creatinine (Scr), blood urea nitrogen (BUN) and blood uric acid (UA), glutamic-pyruvic transaminase (ALT)] and TCM symptom score. The effects and the incidence of type 2 diabetes were evaluated. RESULTS: After treatment, 2 h PG and HbA1c reduced in the two groups (P<0.01, P<0.05) and the results in the embedding group were better (both P<0.05). After treatment, the incidence of hypoglycemia in the embedding group was 0.7% (1/150), and that in the western medication group was 1.3% (2/150), without statistical difference (P>0.05). After treatment, waist circumference and BMI reduced in the two groups (both P<0.01) and the improvements in the embedding group were better (both P<0.05). TC, TG and LDL-C after treatment were lower than those before treatment, and HDL-C were higher in the two groups (all P<0.05), without statistical different values before and after treatment between the two groups (all P>0.05). Scr, BUN, UA and ALT before and after treatment in the two groups had no statistical difference (all P>0.05), without statistical difference after treatment between the two groups (all P>0.05). The TCM score after treatment was lower than that before treatment in the embedding group (P<0.05), and the difference was not statistical in the western medication group (P>0.05). The different value of TCM score in the embedding group was better than that in the western medication group (P<0.01). The total effective rate in the embedding group was 98.0% (147/150), which was superior to 92.7% (139/150) in the western medication group (P<0.05). The incidence of type 2 diabetes was 2.0% (3/150) in the embedding group, and that was better than 7.3% (11/150) in the western medication group (P<0.05). CONCLUSION: Thumb-tack needle for subcutaneous embedding for 2 years could apparent improve the indexes of IGT, which is better than western medication, without liver and kidney damage.

Macrolides for treatment of Haemophilus ducreyi infection in sexually active adults.

BACKGROUND: Chancroid is a genital ulcerative disease caused by Haemophilus ducreyi. This microorganism is endemic in Africa, where it can cause up to 10% of genital ulcers. Macrolides may be an effective alternative to treat chancroid and, based on their oral administration and duration of therapy, could be considered as first line therapy. OBJECTIVES: To assess the effectiveness and safety of macrolides for treatment of H ducreyi infection in sexually active adults. SEARCH METHODS: We searched the Cochrane STI Group Specialized Register, CENTRAL, MEDLINE, Embase, LILACS, WHO ICTRP, ClinicalTrials.gov and Web of Science to 30 October 2017. We also handsearched conference proceedings and reference lists of retrieved studies. SELECTION CRITERIA: Randomized controlled trials (RCTs) comparing macrolides in different regimens or with other therapeutic alternatives for chancroid. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trials for inclusion, extracted data and assessed risk of bias. We resolved disagreements through consensus. We used the GRADE approach to assess the quality of the evidence. MAIN RESULTS: Seven RCTs (875 participants) met our inclusion criteria, of which four were funded by industry. Five studies (664 participants) compared macrolides with ceftriaxone, ciprofloxacin, spectinomycin or thiamphenicol. Low quality evidence suggested there was no difference between the groups after treatment in terms of clinical cure (risk ratio (RR) 1.09, 95% confidence interval (CI) 0.97 to 1.21; 2 studies, 340 participants with syndromic approach and RR 1.06, 95% CI 0.98 to 1.15; 5 studies, 348 participants with aetiological diagnosis) or improvement (RR 0.89, 95% CI 0.52 to 1.52; 2 studies, 340 participants with syndromic approach and RR 0.80, 95% CI 0.42 to 1.51; 3 studies, 187 participants with aetiological diagnosis). Based on low and very low quality evidence, there was no difference between macrolides and any other antibiotic treatments for microbiological cure (RR 0.93, 95% CI 0.74 to 1.16; 1 study, 45 participants) and minor adverse effects (RR 1.34, 95% CI 0.24 to 7.51; 3 studies, 412 participants).Two trials (269 participants) compared erythromycin with any other macrolide type. Low quality evidence suggested that, compared with azithromycin or rosaramicin, long courses of erythromycin did not increase clinical cure (RR 1.00, 95% CI 0.91 to 1.10; 2 studies, 269 participants with syndromic approach and RR 1.04, 95% CI 0.93 to 1.16; 2 studies, 211 participants with aetiological diagnosis), with a similar frequency of minor adverse effects between the groups (RR 1.14, 95% CI 0.63 to 2.06; 1 trial, 101 participants). For this comparison, subgroup analysis found no difference between HIV-positive participants (RR 1.02, 95% CI 0.73 to 1.43; 1 study, 38 participants) and HIV-negative participants (RR 1.04, 95% CI 0.94 to 1.14; 1 study, 89 participants). We downgraded the quality of evidence to low, because of imprecision, some limitations on risk of bias and heterogeneity.None of the trials reported serious adverse events, cost effectiveness and participant satisfaction. AUTHORS' CONCLUSIONS: At present, the quality of the evidence on the effectiveness and safety of macrolides for treatment of H ducreyi infection in sexually active adults is low, implying that we are uncertain about the estimated treatment effect. There is no statistically significant difference between the available therapeutic alternatives for the treatment of sexually active adults with genital ulcers compatible with chancroid. Low quality evidence suggests that azithromycin could be considered as the first therapeutic alternative, based on their mono-dose oral administration, with a similar safety and effectiveness profile, when it is compared with long-term erythromycin use.Due to sparse available evidence about the safety and effectiveness of macrolides to treat H ducreyi infection in people with HIV, these results should be taken with caution.

[Experimental study of cardioprotective and endothelioprotective action of macrolides and azalides].

The cardioprotective and endothelioprotective effects of the macrolide antibiotics roxithromycin, azythromycin, and midecamycin have been studied on laboratory animals with models of the coronaro-occlusional myocardial infarction and endothelial dysfunction. The drugs led to a dose-dependent decrease in lethality, reduced the zone of necrosis of the left ventricle after coronary occlusion, and produced a positive effect on the functioning of endothelium.

Antibiotic use profile at paediatric clinics in two transitional countries.

PURPOSE: In this study, we evaluated antibiotic utilisation pattern at two paediatric clinics in different European (transitional) countries: Croatia (Rijeka) and Russia (Smolensk). METHODS: Antibiotic utilisation during the year 2000 was observed using the ATC/defined daily doses (DDD) methodology (ATC code-J01). Drug-usage data was expressed in numbers of DDD/100 bed-days and the DU90% profile. RESULTS: In Rijeka, 35 different systemic antibiotics were used and in Smolensk 22. The overall consumption of antibiotic drugs in Rijeka was more than three times higher than in Smolensk (28.96 vs 8.3 DDD/100 bed-days). The top five antibiotic drugs used in Smolensk were amoxicillin, mydecamicin, ampicilin, doxycylin, gentamicin; and in Rijeka cefuroxime axetil, ceftriaxone, azytromycin, ceftibuten and amoxicillin. CONCLUSION: Differences in antibiotic prescribing patterns are greater than expected. The pattern of antibiotic utilisation in both countries implies that regional control measures and guidelines for antibiotic use in children should be urgently established.

[Macrolide consumption according to geographic areas in the province of Valladolid]. / Descripción del consumo diferencial de macrólidos por áreas geográficas en la provincia de Valladolid.

AIM: In our setting systemic antibiotics comprise one of the most extensively used treatment groups in Primary Care. Among these, the use of macrolides has increased considerably in recent years and has shown variations in consumption according to geographic areas. This work was performed to quantify these variations. METHODS: Information on macrolide consumption in six geographic areas of the providence of Valladolid over 5 years (1996-2000) was compiled through data provided by International Marketing Services. The indicator used was the defined daily dose per 1,000 inhabitants and day. RESULTS: Macrolide consumption varied considerably among the areas studied. Greatest use of the major macrolides (clarithromycin, erythromycin and spiramycin) was observed in the area of Medina del Campo. Use of the remaining active principles in this subgroup of antibiotics showed the following distribution: midecamycin in the city of Valladolid, azithromycin in Area Norte and roxithromycin in Area Sur. CONCLUSIONS: Macrolide consumption showed significant differences according to areas, with some areas showing double the consumption of others. This diversity indicates specific patterns of use of the antimicrobials in this subgroup.

[Double-blind clinical trial comparing 5 days of dirithromycin versus 7 days of diacetylmidecamycin in acute bronchitis and acute exacerbations of chronic bronchitis]. / Ensayo clínico doble ciego comparando 5 días de diritromicina frente a 7 días de diacetilmidecamicina en bronquitis aguda y exacerbaciones agudas de bronquitis crónica.

BACKGROUND: Dirythromycin has several pharmacokinetic characteristics (long half life and high tissue concentrations) which suggest the possibility of administering shorter treatments than those conventionally used. The aim of this study was to determine and compare the efficacy of a 5 day treatment with dirythromycin once a day, versus diacetylmidecamycin twice a day over 7 days in the treatment of patients with acute bronchitis and acute exacerbations of chronic bronchitis. METHODS: A parallel, multicentric, randomized, double blind clinical study was carried out in 8 Spanish hospitals. RESULTS: One hundred seventy-four patients were included in the study, with 87 (80 evaluable) being randomly assigned to receive dirythromycin (500 mg/day over 5 days) and 87 (83 evaluable) diacetylmidecamycin (600 mg, twice daily over 7 days). A favorable symptomatic response (cure or improvement) was observed in 72/80 of the first group (90%) and in 74/83 (89.2%) of the second group. No statistically significant differences were found in the efficacy and safety between the two treatment groups in either the evaluable patients or on intention to treat analysis. CONCLUSIONS: The results of this study suggest that the administration of dirythromycin, once a day over 5 days, is as safe and effective as diacetylmidecamycin, twice a day over 7 days, in the treatment of acute bronchitis and acute exacerbations of chronic bronchitis.

[A trial of the use of rulid, sumamed and makropen in the combined treatment of generalized periodontitis at a stage of exacerbation]. / Opyt primeneniia rulida, sumameda i makropena v kompleksnom lechenii generalizovannogo parodontita v stadii obostreniia.

In vitro study of the antibacterial activity of macrolide antibiotics azitromycin (sumamed), midicamycin (macropen), roxitromycin (rulide), and erythromycin demonstrated their high activity towards clinical strains of bacteroids, fusobacteria, peptostreptococci, streptococci, and corynebacteria. These antibiotics were effective in the treatment of 62 adult patients with severe and moderate generalized periodontitis. Rulide and sumamed were the most effective, macropen and erythromycin were inferior to them.

[Use of oral macrolide and azalide antibiotics in children with bronchopulmonary diseases]. / Primenenie peroral'nykh makrolidnykh i azalidnykh antibiotikov pri bronkholegochnoi patologii u detei.

The therapeutic efficacy of oral macrolides (erythromycin base and midekamycin, macropen) and azalides (azithromycin, sumamed) in the treatment of children with acute and chronic (during the aggravation) bronchopulmonary diseases was studied. The main etiological factors of acute and chronic pneumonia were Streptococcus pneumoniae and Haemophilus influenzae. The proportion of Staphylococcus aureus was high in infants with acute pleuropulmonary inflammations. The susceptibility of the isolates to the antibiotics was found to be high. The results of the trials showed that erythromycin, macropen and azithromycin were efficient in the treatment of acute and chronic pneumonia. The foci of acute pneumonia dissolved after oral administration of the drugs within the same periods as after the use of other parenteral antibiotics. The comparative estimation of the drug efficacy revealed that azithromycin was more active. The ease of the azithromycin administration (in the form of a suspension) in infants and children once a day for a shorter treatment course up to 5 days, high efficacy and no adverse reactions permitted to consider the antibiotic as the most promising antibacterial agent for the treatment of respiratory infections in children in hospitals and outpatient departments.

Anticellular and antitumor activity of duocarmycins, novel antitumor antibiotics.

The anticellular and antitumor activities of novel antitumor antibiotics, duocarmycins (DUMs), were examined against human and murine tumor cells. DUMs consist of five compounds, A, B1, B2, C1 and C2, which possess a pharmacophore similar to that of CC-1065, a previously isolated antibiotic. Among them, DUMA exhibited ultrapotent growth-inhibitory activity with an IC50 value of 6 pM against human uterine cervix carcinoma HeLa S3 cells. DUMA and DUMB1 also inhibited the growth of adriamycin (ADM)-resistant lines of human nasopharynx carcinoma KB cells and breast carcinoma MCF-7 cells as well as their sensitive lines. DUMs inhibited the growth of s.c.-inoculated murine tumors such as B16 melanoma, sarcoma 180, M5076 sarcoma and colon 26. DUMs were also significantly effective in increasing the lifespan of i.p.-inoculated B16 melanoma-bearing mice, although their effect was marginal against other i.p.-inoculated tumors. As a whole, DUMB1 exhibited superior activity to the other four compounds. DUMB1 rapidly inhibited the incorporation of [3H]-TdR into macromolecules of HeLa S3 cells as compared with that of [3H]UR or [3H]leucine. DNA strand breaks were detected in DUMB1-treated HeLa S3 cells by agarose gel electrophoresis with a contour-clamped homogeneous electric field apparatus. These results indicate that DUMs possess interesting biological activities as DNA-targeting antitumor antibiotics.

[Protocol study and results of the use of midecamycin for bacterial infections of the upper respiratory tract]. / Estudio protocolizado y resultados del empleo de midecamicina en infecciones bacterianas de vías respiratorias altas.

Planned study of 110 patients suffering infections of the upper respiratory tract. Soon after a smear of the focus for bacterial examination was taken a treatment with diacetyl-midecamycin was scheduled during 7 days. Thereafter another control smear and checking of the clinical status was realized. The issue of the study was very good, excepting 3 cases in which the drug was discontinued owing to gastrointestinal intolerance.

Eficácia e tolerabilidade da miocamicina em duas administraçöes diárias no tratamento de infecçöes pediátricas / Clinical efficacy and tolerance of miocamycin, twice a day, in the management of pediatric infections

Trinta e um pacientes pediátricos, na faixa etária de seis meses a nove anos, com infecçöes de pele e vias aéreas superiores e inferiores, foram tratados com miocamicina na dose de 30 mg/kg/dia, de 12/12 horas, por um período de sete a 14 dias. Em um caso o tratamento estendeu-se por 18 dias. Antes do tratamento, em 28 pacientes colheu-se material das lesöes de pele, das amígdalas ou da secreçäo do ouvido, para realizaçäo de cultura e antibiograma com discos de eritromicina, clindamicina, lincomicina, oxacilina e penicilina, e determinaçäo do MIC para a miocamicina. Foram isolados: Staphylococcus aureus, Staphylococcus epidermidis, Streptococcus pyogenes, Pseudomonas, Acinetobacter e Morganella morganii. Vinte e nove pacientes ficaram curados. A tolerabilidade foi ótima em 29 casos. Nos dois restantes, um apresentou vômitos, que cederam com antiémetico, e no outro foi necessária a suspensäo do tratamento devido a vômitos e diarréia

A demonstration of the intrinsic importance of stabilizing hydrophobic binding and non-covalent van der Waals contacts dominant in the non-covalent CC-1065/B-DNA binding.

The comparative DNA binding properties and cytotoxic activity of CDPIn methyl esters (n = 1-5) vs. PDE-In methyl esters (n = 1-3) are detailed in studies which provide experimental evidence for the intrinsic importance of stabilizing hydrophobic binding and non-covalent van der Waals contacts dominant in the CC-1065/B-DNA minor groove binding. High affinity minor groove binding to DNA was established through: (1) the observation of CDPI3 binding (UV) but not unwinding of supercoiled DNA (phi 174 RFI DNA) thus excluding intercalative binding; (2) the observation of CDPI3 binding to T4 phage DNA (UV, delta Tm) in which the major groove is occluded by glycosylation thus excluding major groove binding; (3) the observation of salt (Na+) concentration independent high affinity CDPI3 binding to poly(dA . poly(dT) thus excluding simple electrostatic binding to the DNA phosphate backbone; and further inferred through (4) the observation of an intense induced dichroism (ICD, poly(dA) . poly(dT) and poly(dG) . poly(dC) [phi]23(358) = 24,000 and 23,500). This high affinity minor groove binding is sufficient to produce a potent cytotoxic effect.(ABSTRACT TRUNCATED AT 400 WORDS)

Synthesis and antimicrobial evaluation of 20-deoxo-20-(3,5-dimethylpiperidin-1-yl)desmycosin (tilmicosin, EL-870) and related cyclic amino derivatives.

A series of 20-deoxo-20-cyclic (alkylamino) derivatives of tylosin, desmycosin, macrocin and lactenocin was prepared by reductive amination of the C-20 aldehyde group. The majority of the compounds were prepared using metal hydrides (sodium cyanoborohydride or sodium borohydride) as the reducing agents and a suitable cyclic alkylamine. Subsequently, a more convenient procedure was developed using formic acid as a reducing agent. The C-20 amino derivatives prepared from desmycosin exhibited good in vitro antimicrobial activity against Pasteurella haemolytica and Pasteurella multocida (MIC range of 0.78 approximately 6.25 micrograms/ml) as well as Mycoplasma species (MIC range of 0.39 approximately 6.25 micrograms/ml). Several derivatives showed excellent oral efficacy against infections caused by P. multocida in chicks. One of these derivatives, 20-deoxo-20-(3,5-dimethylpiperidin-1-yl)desmycosin (tilmicosin or EL-870) was selected for development as a therapeutic agent for pasteurellosis in calves and pigs.

Pharmacokinetics of a new macrolide, roxithromycin, in infants and children.

The pharmacokinetics of roxithromycin was investigated after oral administration of 2.5 mg/kg doses given 12 hours apart during 6 days in infants and children. These 18 subjects suffering from a respiratory tract infection were divided into three age groups: group I less than 18 months, group II less than 5 years, group III less than 13 years. At day 6, the elimination plasma half-life had an average value (mean +/- SD) of 19.8 +/- 9.7 h (group I), 21.0 +/- 9.4 h (group II) and 20.8 +/- 6.9 h (group III), respectively. The maximum concentration of roxithromycin (Cmax) was attained between 1 and 2 hours after dosing with mean values of 10.1 +/- 3.0 mg/l (group I), 8.7 +/- 4.9 mg/l (group II), 8.8 +/- 7.0 mg/l (group III). All the calculated pharmacokinetic parameters did not significantly differ from one group to another. The kinetics of roxithromycin in infants and children seemed to be age independent and showed no accumulation after repeated doses. During 12 hours, the plasma concentrations were above MIC of microorganisms generally present in respiratory tract infections. Two daily doses of 2.5 mg/kg of roxithromycin 12 hours apart may be proposed in infants and children.

Comparative antimicrobial activity of the new macrolides against Borrelia burgdorferi.

The in vitro and in vivo activity of the new macrolides azithromycin, clarithromycin and roxythromycin was compared with that of erythromycin against Borrelia burgdorferi. In in vitro tests using ten clinical isolates all macrolides were highly active against Borrelia burgdorferi (MIC90 0.015-0.06 micrograms/ml). Azithromycin was more potent than the other macrolides in experimental animal infection, eradicating the organism in all animals tested at a dosage of 8 mg/kg.

Prevention of bacteremia caused by alpha-hemolytic streptococci by roxithromycin (RU-28 965) in granulocytopenic patients receiving ciprofloxacin.

We previously demonstrated that ciprofloxacin prevents infections caused by gram-negative bacilli in patients with granulocytopenia. However, in patients with intensive cytotoxic treatment leading to severe mucosal damage a high incidence of bacteremias caused by alpha-hemolytic streptococci was seen. In the present study 45 consecutive patients undergoing intensive cytotoxic treatment received a short course of roxithromycin (10 days) in addition to ciprofloxacin for prevention of bacteremias caused by alpha-hemolytic streptococci. The results of this study were compared with the results obtained in previous comparable patients receiving ciprofloxacin alone. During the days with addition of roxithromycin no infections caused by alpha-hemolytic streptococci occurred, while in the control group of 80 patients 16 bacteremias (20%) were seen. Although roxithromycin was shown to antagonize bactericidal action of ciprofloxacin on gram-negative bacilli in vitro, in vivo study based on serum bactericidal titers and on results of surveillance cultures showed no antagonistic interactions.