Suppression of lipopolysaccharide-induced inflammatory responses in RAW 264.7 murine macrophages by aqueous extract of Clinopodium vulgare L. (Lamiaceae)

Ethnopharmacological relevance

The wild basil Clinopodium vulgare L. is commonly used in Bulgarian folk medicine for treatment of irritated skin, mastitis- and prostatitis-related swelling, as well as for some disorders accompanied with significant degree of inflammation (e.g. gastric ulcers, diabetes, and cancer).

Aim of study

To determine the effect of aqueous extract of Clinopodium vulgare L. on LPS-induced inflammatory responses of murine RAW 264.7 macrophages.

Materials and methods

Cell cytotoxicity was evaluated by MTT assay. Protein expression levels were monitored by Western blot analysis. Production of NO and PGE₂ was measured by the Griess colorimetric method and enzyme immunoassay, respectively. Activation of MMP-9 was visualized by gelatin zymography. Cytokine levels were determined by BioPlex assay. Intracellular ROS and free radical scavenging potential were measured by DCFH-DA and DPPH method, respectively. Xanthine oxidase activity was evaluated spectrophotometrically.

Results

The extract suppresses NF-κB activation by preventing Iκ-B phosphorylation and inhibits the phosphorylation of p38 and SAPK/JNK MAPKs. It down-regulates iNOS expression which manifests as a drastic decrease of NO production, inhibits MMP-9 activation, but does not affect COX-2 protein levels and reduces only slightly the released PGE₂. Secretion of IL-1β and Il-10 is greatly reduced, whereas suppression of TNF-α and GM-CSF production is less dramatic. The extract has strong free radical scavenging properties and exerts inhibitory effect on xanthine oxidase activity, which lowers the levels of intracellular ROS.

Conclusion

The study provides evidence for the anti-inflammatory potential of Clinopodium vulgare L. aqueous extract.     

Evolution of the minimally invasive treatment of esophageal achalasia

Thanks to the advent of laparoscopic techniques, the last decade and a half have witnessed a radical change in the treatment of esophageal achalasia. Because of the high success rate of the laparoscopic Heller myotomy, surgery has now become in many centers the first modality of treatment for achalasia. This shift in the treatment algorithm reflects the fact that laparoscopic Heller myotomy with partial fundoplication outperforms nonsurgical approaches, such as balloon dilatation and intrasphincteric botulinum toxin injection.     

Silicone gel breast implant rupture rates: research issues.

Documenting the rate of rupture of silicone breast implants appears to be deceptively easy. Largely because of the phenomenon of "silent rupture," it isn't. The authors explore the various technical biases (selection, misclassification, and confounding) and methodological problems that have plagued much of the research conducted to date. By means of a series of illustrations, they argue that explantation has limited utility. Noninvasive techniques have to be used to gather the proper type of data on the timing and frequency of these events. Only with the proper incidence data will researchers be able to identify better the different mechanisms underlying implant rupture and the relative importance of each. The authors recommend that better and standardized definitions of implant rupture be developed, that greater recognition be given to the technical biases and a greater effort be made to eliminate them from investigations of implant rupture, and that more research be conducted by multidisciplinary teams. Because of the growing awareness of the complexity of this issue, the authors also recommend that properly constituted advisory teams be used to provide comprehensive oversight of future research projects from beginning to end.     

Gastroesophageal reflux disease (GERD) and chest pain

Background

Laparoscopic fundoplication cures heart-burn and regurgitation in patients with gastroesophageal reflux disease (GERD) but its effect on the chest pain that is also experienced by some patients is less clear. Confusion stems from the fact that it is difficult to determine preoperatively whether the chest pain is actually caused by the reflux. Therefore, we designed a study in patients with GERD and chest pain that would assess the value of pH monitoring in establishing a correlation between the symptom and the disease, the predictive value of pH monitoring on the results of surgical treatment, and the outcome of laparoscopic fundoplication on chest pain in patients with GERD.

Methods

Of 487 patients who underwent laparoscopic fundoplication for GERD at our institution between October 1992 and July 2000, 165 (34%) complained of chest pain in addition to heartburn and regurgitation. Their symptoms had been present for an average of 118 months. The pH monitoring tracings were analyzed for a correlation between episodes of reflux and chest pain. The mean length of follow-up was 13 months.

Results

Among the 165 patients with chest pain, the relationship between pain and reflux during pH monitoring was as follows: 39 patients (group A) experienced no chest pain during the study; in 28 patients (group B), chest pain correlated with reflux in ≥40% of instances; in 98 patients (group C), chest pain correlated with reflux in ≥40% of instances. Chest pain improved post-operatively in 65% of group A patients, 79% of group B patients, and 96% of group C patients (group C vs A and B: p<0.05). Heartburn and regurgitation resolved or improved in 97% and 95% of patients, respectively.

Conclusions

These data show that pH monitoring helped to identify a relationship between chest pain and reflux; and when the two coincided, the chest pain was relieved by antireflux surgery.

     

Sublethal actions of copper in abalone (Haliotis rufescens) as characterized by in vivo 31P NMR

The sublethal biochemical actions of copper in live, intact red abalone (Haliotis rufescens) were characterized by in vivo 31P nuclear magnetic resonance spectroscopy (NMR). This non-invasive technique is ideal for examining cellular respiration since critical metabolite concentrations, including phosphoarginine ([PA]), inorganic phosphate ([P(i)]) and [ATP], and the arginine kinase (AK) rate constant, can be monitored in real time. Both metabolite concentrations and enzyme rate constants were measured in abalone during 8-h exposures to 66 microg l(-1) (1.04 microM) and 126 microg l(-1) (1.98 microM) copper (as CuCl2). Significant decreases in [PA] and corresponding increases in [P(i)] resulted, while [ATP] remained constant. In controls [PA], [P(i)] and [ATP] all remained unchanged. Furthermore, both copper concentrations induced a significant elevation in the forward AK rate constant over the basal value of 0.020 +/- 0.002 s(-1). Metabolite levels and enzyme rate constants were also measured during 8-h 66 microg l(-1) copper exposures both before and after a 2-week subchronic exposure to 36 microg l(-1) (0.57 microM) copper. Unlike before the subchronic exposure, no significant changes in [PA], [P(i)] or [ATP] were observed after the 36 microg l(-1) copper treatment, compared with controls. This induced tolerance was also evident from the forward AK rate constant data. Finally, copper accumulation was determined in gill, digestive gland and foot muscle samples. Whereas acute exposure only led to significant accumulation in the gill, copper levels in subchronically exposed abalone were significantly elevated in both the gill and digestive gland, and marginally so in foot muscle. Overall, the gill appears to be the primary site of copper accumulation and toxicity, while the foot and adductor muscles maybe secondarily impacted. The observed metabolic changes may result from insufficient oxygen delivery to the muscles, resulting from mucus accumulation or cytological damage at the gill. In conclusion, abalone acutely exposed to copper pollution may develop asphyxial hypoxia. Since their survival is dependent on adherence to rock surfaces, such a reduction of muscle function could ultimately prove fatal.     

Children's perceptions of strategies for resolving community health problems

We examine children's perceptions of the strategies they would use to resolve community health problems. Qualitative analysis using a grounded theory approach showed that 9- to 10-year-old children could conceptualize a range of solutions to hypothetical community health problems. Children's responses reflected an egocentric perspective, one that was centered on self and peers acting on short-term solutions to the immediate problem. Less frequently, children conceptualized broader structural interventions aimed at removing the problem altogether. Children could name resource persons including their friends, family, school personnel and other people in the community. However, outside of their family and peers, their knowledge was non-specific, i.e. it is doubtful that they would actually be able to access the resources. In light of our findings we discuss several important implications for future research. We note that children are interested in changing community conditions that affect their heath. However, their recognition of their marginalized position in adult society and their perception that adults do not take them seriously may be significant barriers to their participation. We suggest that society must rethink the position and roles that are assigned to children so that their valuable potential is not lost.     

Epilepsy and multiple sclerosis in Sicily: a population-based study

PURPOSE: To evaluate the association between epilepsy and multiple sclerosis (MS), we analyzed the incidence of epilepsy in a population-based incidence cohort of MS in Catania, Sicily. METHODS: According to Poser's diagnostic criteria, 170 incident cases of MS have been identified from 1975 to 1994 in the city of Catania. All these subjects underwent a complete neurological examination to confirm the diagnosis of MS and to identify those patients with a history of seizures. Diagnosis of epilepsy was based on the criteria proposed by the International League Against Epilepsy (ILAE) in 1993, and seizures were classified according to the classification of the ILAE, 1981. RESULTS: From 1975 to 1994, 170 subjects with MS had the clinical onset of the disease. The mean annual incidence of MS was 2.3/100,000 (95% CI, 2.0-2.6). Of the 170 defined MS patients, four developed epilepsy after the onset and also diagnosis of MS, giving an incidence rate of epilepsy of 285/100,000 person years at risk (95% CI, 119-684) and 147.8/100,000 when age adjusted to the world standard population. The cumulative risk of developing epilepsy after the onset of MS, evaluated by using the life-table methods, was zero at 1 year and 1.76% at 5 years. Of these four patients, three were classified as having partial seizures with secondary generalization and one with tonic-clonic seizures. CONCLUSIONS: Our data are consistent with those reported in literature suggesting that the risk of developing epilepsy is threefold higher among MS patients than in the general population.     

A national survey of antimicrobial prophylaxis in adult cardiac surgery across Canada

OBJECTIVE:

To characterize national and regional patterns of antimicrobial prophylaxis in adult cardiac surgery across Canada.

DESIGN:

Retrospective, cross-sectional analysis.

SETTING:

Thirty-three adult cardiac surgical centres across Canada.

INTERVENTIONS:

A one-page questionnaire collecting information regarding institutional demographics and antimicrobial prophylaxis regimens for adult cardiac surgical procedures was mailed to all adult surgical centres across Canada. If a response was not received within one month, a second survey was mailed, followed by a telephone reminder within two weeks of the second mailing.

MAIN RESULTS:

The Overall response rate was 100%. Prophylactic antimicrobials were used in all the adult cardiac centres; single-agent prophylaxis was used in 97% (32 of 33) of centres; Single-dose antimicrobial prophylaxis was used in only 3% (one of 33) of centres. Preoperative and postoperative antimicrobial prophylaxis regimens varied both between provinces and within provinces across Canada. Cefazolin was the antimicrobial used in 88% (38 of 43) and 87% (33 of 38) of the reported pre-operative and post-operative prophylaxis regimens, respectively. Antimicrobial prophylaxis was initiated in the operating room 72% (26 of 36) of the time and intra-operative supplemental antimicrobial doses were administered for cardiac procedures longer than a median of 4 hours (range 4 to 8 hr). Overall, the median duration of antimicrobial prophylaxis was 36 hours (range 8 to 96 hr).

CONCLUSIONS:

Despite the availability of various published guidelines, our survey identified several areas for improvement with respect to antimicrobial prophylaxis in adult cardiac surgery across Canada.Key Words: Antibiotics, Cardiac surgical procedures, Prophylaxis, Surgical wound infectionPostoperative infections complicating cardiac surgery are associated with serious complications (e.g. mediastinitis, osteomyelitis, sternal wound infections and endocarditis), that result in significant morbidity, mortality, and increased costs (1-3). Despite evidence that antimicrobial prophylaxis is beneficial in reducing these complications, the optimal prophylactic regimen in cardiac surgery has not been defined (4-8). According to the 1999 Guidelines for Coronary Artery Bypass Graft Surgery from the American College of Cardiology (ACC) and the American Heart Association (7), "Many centres, including those with training programs in cardiothoracic surgery, are not consistent in delivering or teaching effective use of perioperative antibiotics".Although antimicrobial prophylaxis practice patterns in cardiac surgery have been documented for other geographical regions, the antimicrobial prophylaxis practice in adult cardiac surgery across Canada has not been documented to date (9-13). This information, in conjunction with the available literature, would be extremely useful for the development and/or revision of local guidelines for antimicrobial prophylaxis in cardiac surgery.The objective of this nationwide survey was to characterize national and regional patterns of antimicrobial prophylaxis in adult cardiac surgery across Canada.     

Prolonged survival and low incidence of late toxic sequelae in advanced follicular lymphoma treated with a TBI-free autografting program: updated results of the multicenter consecutive GITMO trial.

This study provides an updated report of the consecutive multicenter Gruppo Italiano Trapianto Midollo Osseo trial employing an intensified, purging-free, total body irradiation-free, high-dose sequential chemotherapy schedule with peripheral blood stem cell autograft (i-HDS) in advanced-stage follicular lymphoma (FL). Special interest has been devoted to late toxicities and outcome in terms of molecular status. Ninety-two untreated FL patients aged 相似文献