Comparative Human Oral Clinical Pharmacology of Cefadroxil, Cephalexin, and Cephradine

At equivalent oral doses, cefadroxil has a longer serum half-life, slower urinary excretion rate, greater area under the serum level versus time curve than cephalexin or cephradine, and peak serum concentrations that are 75 to 80% those of cephalexin. The calculated, apparent in vivo volume of distribution of cefadroxil is greater than that of cephalexin. These properties infer greater persistence of cefadroxil in serum and urine and more prolonged in vivo bacterial exposure to cefadroxil than to cephalexin or cephradine. Neither cefadroxil nor cephalexin demonstrates drug accumulation on repeated administration. The serum levels achieved by cefadroxil are unaffected by food. The pharmacokinetic properties of cefadroxil are supportive of the development of clinical efficacy data which could indicate that cefadroxil could be administered at 12-h intervals.     

Propolis-induced genotoxicity and antigenotoxicity in Chinese hamster ovary cells.

Propolis has been used in folk medicine since ancient times and is known for its antimicrobial, antiparasitic, antiviral, anti-inflammatory, antitumoral and antioxidant properties. In view of the great therapeutic interest in propolis and the small number of studies regarding its mechanism of action, the aim of the present study was to evaluate the mutagenic and antimutagenic effects of propolis using Chinese hamster ovary cells. Parameters such as the frequency of chromosome aberrations and mitotic index were analyzed. The results showed that, on one hand, the highest propolis tested concentration displayed a small but significant increase in the frequency of chromosome aberrations, and on the other hand, it was observed that the lowest tested concentration significantly reduced the chromosome damage induced by the chemotherapeutic agent doxorubicin. The present results indicate that propolis shows the characteristic of a "Janus" compound, i.e., propolis is genotoxic at higher concentrations, while at lower concentrations it display a chemopreventive effect on doxorubicin-induced mutagenicity. Flavonoids may be the components of propolis responsible for its both mutagenic and antimutagenic effects, once these compounds may act either as pro-oxidant or as free radicals scavenger, depending on its concentration.     

Effect of Solanum nudum Dunal (Solanaceae) steroids on hepatic trophozoites of Plasmodium vivax

Steroids isolated from the plant Solanum nudum showed antiplasmodial activity against the blood stages of Plasmodium falciparum. It has been demonstrated that these steroids are neither mutagenic in vitro nor clastogenic in vivo. This study evaluated the effect of five steroids of S. nudum (SN-1, SN-2, SN-3, SN-4 and SN-5) on hepatic trophozoites of P. vivax, using an experimental design, non-balanced, with blind determination of the effect expressed as the percentage reduction of hepatic trophozoites. The sporozoites used to inoculate human hepatoma cells HepG2-A16 were obtained from gametocytemic blood of volunteers infected only with P. vivax, and passed into laboratory-reared Anopheles albimanus mosquitoes. Steroids were added at three different doses (100, 10 and 1 microg/mL) just after inoculation of the cells with sporozoites. The effect was determined by indirect immunofluorescence assays using the monoclonal antibodies Pv210 or Pv47E-2E10 and steroid cytotoxicity on HepG2-A16 cells was assessed by the MTT method. All the steroids reduced the number of hepatic P. vivax trophozoites, SN-2 and SN-4 reduced the number of hepatic trophozoites by 47% and 39% (p < 0.05), respectively.     

Gastric antiulcer and anti-inflammatory activities of the essential oil from Casearia sylvestris Sw

To investigate the antiulcer and antiinflammatory activities of the essential oil from Casearia sylvestris leaves (EOCS) the following tests were used: rat paw edema, granulomatous tissue test, vascular permeability, writhing test, gastric ulcer stress-induced and evaluation of gastric secretion (pylorus ligation test). The total yield of EOCS was 2.5% with LD50 of 1100 mg/kg in mouse. The major compounds identified using gas chromatography were caryophyllene, thujopsene, alfa-humulene, beta-acoradiene, germacrene-d, bicyclogermacrene, calamenene, germacrene B, spathulenol and globulol. The EOCS orally administered to the rats at 125 mg/kg resulted 36% of inhibition in carrageenan-induced edema in the rat paw assay (p<0.05, Student's t-test). However, both rat paw edema dextran-induced and vascular permeability assay using histamine showed no significant inhibition. Mice submitted to the writhing test using acetic acid presented 58% and 56% of inhibition in writhes with EOCS and indomethacin, respectively. Furthermore, EOCS inhibited 90% of stress-induced gastric ulcer, while cimetidine inhibited 70% (p<0.05, Student's t-test). The volume of gastric secretion in the group treated with EOCS was greater than the group treated with cimetidine. The EOCS also showed no changes related to H+ levels in the gastric secretion. With the overall results obtained in this study the authors suggest an anti-inflammatory activity for the EOCS of Casearia sylvestris beyond its anti-ulcer activity.     

(4-Methoxyphenyl)(3,4,5-trimethoxyphenyl)methanone inhibits tubulin polymerization,induces G2/M arrest,and triggers apoptosis in human leukemia HL-60 cells

(4-Methoxyphenyl)(3,4,5-trimethoxyphenyl)methanone (PHT) is a known cytotoxic compound belonging to the phenstatin family. However, the exact mechanism of action of PHT-induced cell death remains to be determined. The aim of this study was to investigate the mechanisms underlying PHT-induced cytotoxicity. We found that PHT displayed potent cytotoxicity in different tumor cell lines, showing IC₅₀ values in the nanomolar range. Cell cycle arrest in G₂/M phase along with the augmented metaphase cells was found. Cells treated with PHT also showed typical hallmarks of apoptosis such as cell shrinkage, chromatin condensation, phosphatidylserine exposure, increase of the caspase 3/7 and 8 activation, loss of mitochondrial membrane potential, and internucleosomal DNA fragmentation without affecting membrane integrity. Studies conducted with isolated tubulin and docking models confirmed that PHT binds to the colchicine site and interferes in the polymerization of microtubules. These results demonstrated that PHT inhibits tubulin polymerization, arrests cancer cells in G₂/M phase of the cell cycle, and induces their apoptosis, exhibiting promising anticancer therapeutic potential.     

Specificity of L1 peptides versus virus-like particles for detection of human papillomavirus-positive cervical lesions in females attending Engativa Hospital, Bogota, Colombia

A serological test for the detection of human papillomavirus (HPV) infection in females at risk of developing cervical cancer could be based on conserved L1 peptides with low levels of antigenicity specifically recognized by antibodies from patients with cervical lesions infected with high-risk HPV (HR-HPV) types. The aim was to assess the ability of L1 peptides 18283, 18294, and 18301 compared with the ability of virus-like particles (VLPs) to identify these infections in females. A total of 391 HPV-infected female volunteers were interviewed, and peripheral blood and cervical cells were obtained for detection of anti-HPV antibodies and HPV DNA; all of the patients had a Pap smear test; 287 patients were referred for colposcopy or biopsy, according to gynecological criteria. The level of agreement, as determined by the use of the Lin coefficient (rho value), showed that 75 to 83% of females with HR-HPV DNA-positive cervical lesions had antibodies that recognized VLPs and peptide 18283, 18294, or 18301, while 15 to 23% of the HPV DNA-negative females with a normal cytology had antibodies that recognized these three peptides and 45% had antibodies that recognized VLPs. The rate of agreement between peptides and VLPs for antibody detection was higher for patients with HPV DNA-positive cervical lesions. Peptides 18283, 18294, and 18301 showed similar sensitivities for the detection of HR-HPV DNA-positive cervical lesions and were more specific than VLPs. Peptide 18301 might be detecting protective antibodies in HPV DNA-negative females with atypical squamous cells of undetermined significance. These peptides could be useful for the design of a serology test for the detection of HR-HPV infection in females with cervical lesions and at risk of cervical cancer.     

Clinical application of Chamomilla recutita in phlebitis: dose response curve study

This experimental and dose-response curve study aimed to carry out the quality control of the Chamomilla recutita sample, as well as to estimate the ideal dose, for anti-inflammatory effect, of the extract of its capitula, in patients with phlebitis due to peripheral intravenous infusion of antineoplastic chemotherapy and to evaluate the toxicity of this extract in human beings. The therapeutic efficacy, concerning the anti-inflammatory potential, of different doses of Chamomilla recutita extract were analyzed and compared in 25 patients. The time of regression of phlebitis was shorter for groups with 2.5% concentration (mean=29.2h, standard deviation = 8.98) and 5% concentration (mean = 38.8h, standard deviation = 17.47). Local toxicity was almost not observed. This research contributes to the innovation of the nursing clinical practice, since it suggests an alternative for the treatment of phlebitis through the clinical use of phytotherapeutic drugs.     

High mortality, violence and crime in alcohol dependents: 5 years after seeking treatment in a Brazilian underprivileged suburban community

ObjectiveTo investigate the results of alcohol-related consequences in an underprivileged area of São Paulo.MethodOne hundred and ninety one adult patients who sought alcohol treatment in 2002 were reassessed in 2007 regarding alcohol use and involvement with crime. The interview consisted of demographic questions and questionnaires assessing alcohol dependence and pattern of alcohol use. Risk and protective factors and involvement with crime were further explored.ResultsHigh mortality rate (16.9%, n = 41) was found in this sample and 97.4% were identified as being severe alcohol dependents. The sample consisted of a homogeneous group, average age of 42, 81.9% male, 57.5% black, 52.2% unemployed and 100% of low socioeconomic status. Individuals ageing 35 or younger, not engaged in religious activities and with intense alcohol consumption in the last month had 2.7 times more chance on committing crimes (95% CI = [1.22; 5.93] p = 0.014). Subjects who consumed alcohol in the last month also had a 4.1 greater chance of becoming involved in crime (95% CI = [1.2; 14.24] p = 0.024).ConclusionAlcohol dependence within an underprivileged community was associated with high rates of crime and mortality. Religious affiliation was negatively associated with delinquent behavior.