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PubMed1996

Agent and nature of childhood injury and initial care provided at the community level in Ibadan, Nigeria.

Daily home interviews-examinations were carried out for a period of three months to obtain information on the agent (object) involved, nature (diagnosis) and care provided to children aged zero to 19 years, following accidental injury, in Idikan community, Ibadan. During the study period, 1286 injuries were recorded involving all the 436 children in the study community. Rocky outcrops, chairs, broken bottles, tables, knives and glasses were the major agents of injuries (91.0%). Puncture wounds, lacerations, haematomas, sprains and dislocations constituted most of the nature of injury (96.5%). All injuries were minor injuries (AIS = 1). Relatives-neighbours were responsible for managing majority of the injuries. Only seven (0.6%) injuries were seen by a nurse-physician in a health facility. Specific individual-community health education as well as health service and environmental modification measures are suggested. This study has also shown that community based data on injury provides more precise information required for the development of injury prevention and care programmes at the primary care level.

Accident Prevention↗
PubMed2005

Construction and analysis of a Mannheimia haemolytica A1 luxS mutant.

Mannheimia haemolytica A1 is the causative agent of bovine pneumonic pasteurellosis, a major cause of sickness, death, and economic loss to the feedlot cattle industry. M. haemolytica A1 produces autoinducer-2 (AI-2) like molecules that are capable of inducing quorum sensing system 2 of Vibrio harveyi. This interspecies quorum sensing system has been shown to regulate the expression of virulence genes in several pathogenic bacteria. The protein central to the production of AI-2 is LuxS. To determine if quorum sensing is involved in the regulation of virulence genes in M. haemolytica A1, a luxS mutant was constructed by replacing luxS with a cat cassette. This mutant was verified by PCR analysis, Southern hybridization, as well as its inability to induce bioluminescence in the V. harveyi reporter strain. RT-PCR analysis showed there was no difference in leukotoxin (lktC) mRNA levels, however there were increased mRNA levels of putative virulence associated genes, transferrin binding protein B (tbpB), adhesin (ahs) and capsule biosynthesis (nmaA). Electron microscopy showed that the level of encapsulation in the mutant is higher than the parent. Additionally, the mutant was slightly more adherent to bovine tracheal cells than the parent. In vitro competition assays showed the mutant out-competed the parent under iron-restricted conditions. However, in a calf challenge, the parent was the dominant isolate recovered.

Animals↗
PubMed2004

Seasonal distribution of acute myocardial infarction and its relation to acute infections in a mild climate.

BACKGROUND: There is evidence that acute myocardial infraction (aMI) occurs more frequently in certain seasons and months of the year. Recently various infectious agents have been implicated in atherogenesis. In the present study we recorded the seasonal distribution of aMI and evaluated its relation to acute systemic infections (AIs). METHODS: The study included 1196 patients with aMI hospitalized during the years 1988-1998 in the General Hospital of the island of Rhodes and 2976 patients with AI during the years 1993-1998. Foreigners or visitors in the island were excluded to avoid their influence in the annual distribution. We corrected the absolute number of the aMI and AI cases by month and season in such a way that all months and seasons would have standard 30 and 90 days, respectively. RESULTS: During the entire period of the study, more patients with aMI were hospitalized in winter [30.7%, 95% confidence limits (CL) 28.1 to 33.3%]. In spring the percentage of aMI cases hospitalized was 24.5% (CL 22.1-27%), in summer 23.2% (CL 20.1-25.6%) and in autumn 21.6% (CL 19.2 -24%). There were 42.35% more cases hospitalized in winter than in autumn. The monthly distribution showed that March was the month with the most aMI cases (10.83%, CL 9.06-12.6% ) and October with the fewest (6%, CL 4.65-7.35%). The percentage of patients with AI hospitalized in winter was 30.5% (CL 28.8-32.2%), in spring 25.2% (23.6-26.7), in summer 23.5% (CL 22-25%) and in autumn 20.8% (CL 19.4-22.3%). The correlation coefficient (r) between the distribution of aMI and AI was 0.73 (P<0.01). CONCLUSIONS: Our results indicate that (1) there is a seasonal distribution in aMI with the winter being the season of the highest incidence of aMI and autumn of the lowest and (2) there is a significant correlation of the distribution of aMI to AI cases, which is of interest in the understanding of the pathogenesis of acute coronary syndromes.

Acute Disease↗
PubMed2004

Selective oestrogen receptor modulators/new antioestrogens: a clinical perspective.

Following tamoxifen, the first selective oestrogen receptor modulator (SERM), a number of other antioestrogens have been developed. The first-generation SERMs exhibit cross-resistance with tamoxifen and have agonist effects on the uterus. Toremifene has equal efficacy to tamoxifen and may be useful as a tamoxifen alternative. Efficacy results for droloxifene and idoxifene were disappointing and their clinical development ceased. Response rates for second-generation SERMs such as raloxifene and arzoxifene are also not high, although raloxifene shows promise in the chemoprevention of breast cancer. Paradoxically, high-dose oestrogens are proving to be effective breast cancer treatment with similar responses to tamoxifen in postmenopausal women with advanced disease, although these drugs are not well tolerated. Fulvestrant is a new type of oestrogen receptor (ER) antagonist with no agonist effects, which binds, blocks and degrades the ER. Fulvestrant produces high response rates compared with the SERMs, is not cross-resistant with SERMs or aromatase inhibitors (AIs) and is equally as effective as the AI anastrozole in the treatment of postmenopausal women with advanced breast cancer who have progressed after prior antioestrogen therapy. Pure antioestrogens such as the ER antagonist fulvestrant provide opportunities for therapeutic sequencing with tamoxifen and AIs and offer exciting possibilities for the future treatment of breast cancer.

Antineoplastic Agents, Hormonal↗
PubMed2001

[Genotyping mycobacteria, isolated from incarcerated tuberculosis patients].

The aim of the investigation was to genotype clinical Mycobacterium tuberculosis isolates circulating at the penitentiaries of the Ivanovo Region. Mycobacterial strains were genotyped by the polymorphism of the lengths of restrictive fragments containing the insertion sequence 6110 by the routine procedure. The genotypes of Mycobacterium strains were classified in accordance with the PHRI database (New York). The strains were characterized by their sensitivity to antituberculous drugs by the absolute concentration method. The investigations indicated that in terms of the IS6110 genotype there were prevalent Mycobacteria strains belonging to 2 families: a W family (62.5% of the strains) and an AI family (25%). In addition to the monocultures, genotyping also revealed 3 mixed cultures consisting of 2 strains. Determining the drug sensitivity of the genotyped strains demonstrated both drug-sensitive and drug-resistant strains, including multidrug resistance among the strains of the same genotyping family (W or AI).

Antitubercular Agents↗
PubMed1994

Action of nitrogenated and sulfonylated inositol derivatives upon the proliferation in vitro of normal mouse cells and tumor mouse cells.

Despite the major advances of cancer chemotherapy during the past 40 years, host toxicities and drug resistance justify the need to continue the search for new antineoplastic agents. In the present work, we have studied the effect of six synthetic drugs on the in vitro growth of two murine mammary adenocarcinomas (M3 and MM3), as well as on normal embryonic cells. AI, MIC and MPI are purines coupled to a sulfonylated inositol, while DIC and DEI have nitrogen mustard as substituent. Methylsulfonylmucoinositol was the common substituent. Our results indicated that only drugs substituted with nitrogen mustards had an antiproliferative effect. DEI was more effective on tumor cells than on normal cells.

Adenocarcinoma↗
PubMed2003

Antibacterial activity and mechanism of action of tick defensin against Gram-positive bacteria.

Defensins are a major group of antimicrobial peptides and are found widely in vertebrates, invertebrates and plants. Invertebrate defensins have been identified from insects, scorpions, mussels and ticks. In this study, chemically synthesized tick defensin was used to further investigate the activity spectrum and mode of action of natural tick defensin. Synthetic tick defensin showed antibacterial activity against many Gram-positive bacteria but not Gram-negative bacteria and low hemolytic activity, characteristic of invertebrate defensins. Furthermore, bactericidal activity against pathogenic Gram-positive bacteria including Bacillus cereus, Enterococcus faecalis and methicillin-resistant Staphylococcus aureus was observed. However, more than 30 min was necessary for tick defensin to completely kill bacteria. The interaction of tick defensin with the bacterial cytoplasmic membrane and its ability to disrupt the membrane potential was analyzed. Tick defensin was able to disrupt the membrane potential over a period of 30-60 min consistent with its relatively slow killing. Transmission electron microscopy of Micrococcus luteus treated with tick defensin showed lysis of the cytoplasmic membrane and leakage of cellular cytoplasmic contents. These findings suggest that the primary mechanism of action of tick defensin is bacterial cytoplasmic membrane lysis. In addition, incomplete cell division with multiple cross-wall formation was occasionally seen in tick defensin-treated bacteria showing pleiotropic secondary effects of tick defensin.

Amino Acid Sequence↗
PubMed2026

Cationic porphyrin covalent organic framework reinforced hydroxypropyl methylcellulose films for photodynamic-photothermal sterilization and food preservation.

Microbial contamination in food necessitates effective antimicrobial packaging. While cellulose-based packaging materials suffer from limited antimicrobial efficacy, lack of active functionality, and susceptibility to inducing microbial resistance. To address these challenges, this study synthesized a cationic porphyrin-based covalent organic framework (Por-ICOF) as a multimodal photosensitizer. Por-ICOF was uniformly dispersed via non-covalent interaction within hydroxypropyl methylcellulose (HPMC), creating an HPMC/Por-ICOF composite film. This integration enhanced mechanical strength (increased by 26%), hydrophobicity (WCA 71&#xb0;), and gas barrier properties (OP reduced by 42%, WVP reduced by 36%). Under visible light, the HPMC/Por ICOF film superior absorption generated reactive oxygen species (ROS) and photothermal effects, inactivating 99.2% of Escherichia coli and 99.95% of Staphylococcus aureus within 20&#xa0;min. The composite film exhibited excellent biocompatibility and effectively extended the shelf life of strawberries. This cationic modification strategy for cellulose-based films offers a novel avenue for the design of high-performance antimicrobial food packaging materials.

Food Preservation↗
PubMed2004

Antiviral activity of a serine protease from the digestive juice of Bombyx mori larvae against nucleopolyhedrovirus.

A protein showing strong antiviral activity against Bombyx mori nucleopolyhedrovirus (BmNPV) was purified from the digestive juice of B. mori larvae. The molecular mass of this protein was 24271 Da. Partial N-terminal amino acid sequence of the protein was determined and cDNA was cloned based on the amino acid sequence. A homology search of the deduced amino acid sequence of the cDNA showed 94% identity with B. mori serine protease so the protein was designated B. mori serine protease-2 (BmSP-2). Analysis of BmSP-2 gene expression showed that this gene is expressed in the midgut but not in other tissues. In addition, BmSP-2 gene was shown to not be expressed in the molting and wandering stages, indicating that the gene is hormonally regulated. Our results suggest that BmSP-2, an insect digestive enzyme, can be a potential antiviral factor against BmNPV at the initial site of viral infection.

Amino Acid Sequence↗
PubMed2003

Scarabaecin, a novel cysteine-containing antifungal peptide from the rhinoceros beetle, Oryctes rhinoceros.

A novel antifungal peptide, scarabaecin (4080Da), was isolated from the coconut rhinoceros beetle, Oryctes rhinoceros. Scarabaecin cDNA was cloned by reverse transcriptase-polymerase chain reactions (RT-PCR) using a primer based on the N-terminal amino acid sequence. The amino acid sequence deduced from scarabaecin cDNA showed no significant similarity to those of reported proteins. Chemically synthesized scarabaecin indicated antifungal activity against phytopathogenic fungi such as Pyricularia oryzae, Rhizoctonia solani, and Botrytis cinerea, but not against phytopathogenic bacteria. It showed weak activity against Bauberia bassiana, an insect pathogenic fungus, and Staphylococcus aureus, a pathogenic bacterium. Scarabaecin showed chitin binding property and its K(d) was 1.315 microM. A comparison of putative chitin-binding domains among scarabaecin, invertebrate, and plant chitin-binding proteins suggests that scarabaecin is a new member of chitin-binding antimicrobial proteins.

Amino Acid Sequence↗
PubMed2005

Pharmacokinetic changes of irinotecan by intestinal alkalinization in an advanced colorectal cancer patient.

The prevention of irinotecan (CPT-11)-induced diarrhea, a well-known adverse reaction to the drug, by treatment with intestinal alkalinization has been carried out in patients with colorectal cancer in Japan. Under acidic conditions, CPT-11 and its active metabolite, SN-38, exists preferably as the lactone form, whereas both exist as the carboxylate form under basic conditions. It has been suggested that the lactone forms of both CPT-11 and SN-38 are diffused passively across the intestinal mucosal membranes, whereas the carboxylate forms are actively transported. The intestinal uptake rate of both forms appears to be pH sensitive under physiological conditions, but it remains unclear whether intestinal alkalinization treatment affects the pharmacokinetics of CPT-11 and SN-38. This study was designed to evaluate the pharmacokinetics of CPT-11 and SN-38 in a colorectal cancer patient with or without alkalinization treatment. We found that intestinal alkalinization significantly decreased the plasma levels of CPT-11 and SN-38. In particular, the AUC of SN-38 was markedly decreased to 56 from 107 ng.h/mL. Intestinal alkalinization was effective in preventing CPT-11-induced diarrhea, but this treatment changed the pharmacokinetics of CPT-11 and SN-38 in the body.

Antineoplastic Agents, Phytogenic↗
PubMed2005

Medication error in the care of HIV/AIDS patients: electronic surveillance, confirmation, and adverse events.

BACKGROUND: Medication error occurring during the care of HIV-infected patients may lead to treatment failure, drug toxicity, or even death. OBJECTIVE: The objective of this study was to ascertain and confirm 5 categories of medication error in the care of HIV-infected patients. RESEARCH DESIGN: This study was a retrospective study to describe the occurrence of preventable medication error and to determine if adverse events were associated with confirmed errors. A roster of medications for each category of potential errors was created. Computerized pharmacy records were scanned for all dispensing of these medications. Potential errors were confirmed by medical records abstraction. For the incorrect dosing, coadministration of contraindicated medications, and antiretroviral monotherapy error categories, random samples were chart reviewed for confirmation. For the remaining 2 error categories, all potential errors were chart reviewed. The positive predictive value (PPV) of potential errors, the incidence of confirmed error among all new prescription orders filled and the patient characteristics predicting likelihood of error confirmation were estimated for each error category. SUBJECTS: The study sample involved 5473 HIV-infected patients of the Kaiser Permanente Northern California (KPNC) health plan. RESULTS: Among the 5 error categories, PPVs ranged from a high of 80% for coadministration of contraindicated medications to <1% for antiretroviral monotherapy. Incidence of confirmed errors was 9.80 errors per 1000 new prescriptions dispensed for incorrect dosing, 9.51 errors per 1000 for contraindicated medications, and <1.00 for all other categories. Adverse events associated with confirmed errors were observed only in the contraindicated medications error category. The likelihood of a contraindicated medications error was significantly increased among patients >or=50 years of age and decreased among black patients. CONCLUSIONS: Use of electronic pharmacy records to ascertain true medication errors appears most reliable when conducting surveillance for contraindicated medications errors and less reliable for other error categories. Lack of confirmation is likely the result of patients' lack of adherence to drug regimens or providers' intentional deviation from accepted prescribing guidelines. Only confirmed contraindicated medications errors appear to be linked to adverse events.

AIDS-Related Opportunistic Infections↗
PubMed2004

The rdxA gene plays a more major role than frxA gene mutation in high-level metronidazole resistance of Helicobacter pylori in Taiwan.

BACKGROUND: Metronidazole-resistant H. pylori associating with mutations of rdxA or frxA is still a debated topic. This study investigates whether rdxA and frxA mutations of H. pylori accounted for the high MIC value (>/= 64 micro g/ml) of metronidazole (Mtz). MATERIAL AND METHODS: From 126 clinical H. pylori isolates, we examined 14 Mtz-sensitive, 18 Mtz-resistant H. pylori, and eight pairs of Mtz-sensitive and Mtz-resistant colonies simultaneously present within a single gastric biopsy. The paired strains from one single biopsy were proven identical by PCR-RFLP. MICs of Mtz were checked by the E-test and agar dilution method. The mutations of rdxA and frxA sequencing were matched with the Mtz-susceptible ATCC 26695 and J99. RESULTS: There were 89% (16/18) of Mtz-resistant isolates with mutation of RdxA. Half of the 14 Mtz-sensitive strains, all without mutation of RdxA, still contained truncation of FrxA. Within the paired isolates from a single biopsy, rdxA mutation (86%) was more common than frxA mutation (43%) in those isolates with high-level Mtz-resistant H. pylori. RdxA truncation was more prevalent in Mtz-resistant strains with high MICs than in those with low to moderate MICs (75% vs. 20%, p =.01, OR: 12, 95% CI: 1.8-81.7). CONCLUSION: Mutations in the rdxA gene rather than the frxA gene generally determine a high MIC level of Mtz-resistant H. pylori in Taiwan.

Amino Acid Sequence↗
PubMed2007

Cardioprotective effects of diltiazem reevaluated by a novel myocardial ischemic model in Chinese miniature swine.

AIM: To develop a new model of myocardial ischemia in Chinese miniature swine and reevaluate the cardioprotective effects of diltiazem. METHODS: Myocardial ischemia was induced by injecting self-embolus into the left anterior descending (LAD) coronary artery in qualified miniature swine. Diltiazem (5 mg. kg(-1). d(-1)) was orally administered to the swine by mixing into normal pig diet from 1 to 6 d after self-embolus injection. The coronary angiography, 30 point body surface electrocardiogram (BS-ECG), hemodynamics, biochemistry, quantitative histology and pathohistology were determined 6 d after self-embolus injection. RESULTS: Embolization occurred in the LAD coronary artery of the Chinese miniature swine injected by self-embolus. There were significant myocardial ischemia and large cardiac muscle infarction in the Chinese miniature swine, which were accompanied with increased BS-ECG, decreased hemodynamic indexes of the cardiac output, cardiac index, left cardiac work and left cardiac work index, and increased systemic vascular resistance index. Pathohistological analysis revealed myocardial degeneration, necrosis, fibrosis, inflammatory cell infiltration and granulation tissue hyperblastosis (n=6). Diltiazem diminished the extent of the LAD embolism, ameliorated myocardial ischemia, improved the hemodynamic indexes, increased the plasma superoxide dismutase activity, decreased the plasma malondialdehyde content, narrowed the myocardial ischemic area and weakened the pathohistological damage in the cardiac muscle (n=6). CONCLUSION: Myocardial ischemia induced by injecting self-embolus into the LAD coronary artery in Chinese miniature swine is quite close to clinical pathophysiological conditions. Diltiazem is effective to inhibit the myocardial ischemia and restore the heart function in this novel model.

Administration, Oral↗
PubMed2003

A lipase isolated from the silkworm Bombyx mori shows antiviral activity against nucleopolyhedrovirus.

A protein showing strong antiviral activity against Bombyx mori nucleopolyhedrovirus (BmNPV) was purified from the digestive juice of B. mori larvae. A homology search of the deduced amino acid sequence of the protein cDNA revealed 56% homology with Drosophila melanogaster lipase and 21% homology with human lipase. As lipase activity of the protein was confirmed in vitro, this protein was designated Bmlipase-1. Northern blot analysis showed that the Bmlipase-1 gene is expressed in the midgut but not in other tissues, nor is it activated by BmNPV infection. In addition, the Bmlipase-1 gene was shown not to be expressed in the molting and wandering stages, indicating that the gene is hormonally regulated. Our results suggest that an insect digestive enzyme has potential as a physiological barrier against BmNPV at the initial site of viral infection.

Amino Acid Sequence↗
PubMed2003

Suppressive effects of a Chinese herbal medicine qing-luo-yin extract on the angiogenesis of collagen-induced arthritis in rats.

Qing-Luo-Yin (QLY), a traditional Chinese herbal medicine for the treatment of rheumatoid arthritis, is a combination of the extracts of Sophora flavescens Ait., Phellodendron amurense Rupr., Sinomenium acutum Rehd. et Wils. and Dioscorea hypoglauca Palib. The suppressive effect of QLY on the development of angiogenesis was investigated in a rat model of collagen-induced arthritis (CIA). QLY (0.3 g/kg) was orally administered daily for 27 days. Neo-angiogenesis, pannus and cartilage damage, the expression of metalloproteinases (MMP)-3 messenger RNA (mRNA) and the level of the tissue inhibitor of matrix metalloproteinase (TIMP)-1 in the synovium were examined by histology, in situ hybridization and immunohistochemiscal assays, respectively. It was observed that the articular morphological alterations, the over-expression of MMP-3 mRNA and the reduced production of TIMP-1 in CIA rats were significantly ameliorated by QLY. QLY performed about as effectively as tripterygium glycosidorum tablets (0.1 g/kg) extracted from Tripterygium wilfordii Hook. f.. These results indicate that QLY exerts a suppressive effect on the angiogenesis of CIA rats, and suggest that the therapeutic effect of QLY could be due to restoring the balance of MMP-3 and TIMP-1 in rheumatoid synovium.

Animals↗
PubMed2002

Explaining interindividual variability of docetaxel pharmacokinetics and pharmacodynamics in Asians through phenotyping and genotyping strategies.

PURPOSE: To explain the variability of docetaxel pharmacokinetics through study of CYP3A phenotype and genotype, and MDR1 genotype. PATIENTS AND METHODS: We studied the pharmacokinetics and pharmacodynamics of docetaxel in patients in whom it was indicated and who had not received known CYP3A4 substrates. Midazolam was administered intravenously to these patients at least 2 days before docetaxel treatment, and systemic clearances of both drugs were correlated. Patients were characterized for polymorphisms in the CYP3A4 promoter region, CYP3A5, and the C3435T polymorphism of MDR1. RESULTS: Thirty-two patients were enrolled, of whom 31 had full pharmacokinetic data sets. Docetaxel clearance correlated with midazolam clearance, body-surface area, serum albumin, and performance status. Docetaxel and midazolam clearances were normally distributed. In multiple linear regression analyses, midazolam clearance and performance status were the only significant covariates of docetaxel clearance, and the area under the curve of docetaxel, serum levels of alpha-1-acid glycoprotein, and ALT were significant predictors of nadir neutrophil count. No polymorphisms were detected in the 5' regulatory region of CYP3A4. Nine patients of 25 studied were homozygous for the CYP3A5*3 genotype, and had lower mean clearance of midazolam but not docetaxel. The T/T genotype at the C3435T of MDR1, which is associated with reduced P-glycoprotein function, was found in eight of 27 patients. CONCLUSION: Midazolam may be used as a probe drug for CYP3A activity to predict docetaxel clearances, hence reducing interindividual variability. Homozygotes for CYP3A5*3 and C3435T of MDR1 are common in our population, and their effects on pharmacokinetics of relevant substrates should be studied further.

Adult↗