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Purpose: Midazolam has analgesic effects mediated by gamma aminobutyric acid-A receptors. This study was designed to evaluate the effect of midazolam on anesthesia and analgesia quality when added to lidocaine for intravenous regional anesthesia (IVRA)., Methods: Forty patients undergoing hand surgery were randomly assigned to two groups to receive IVRA. The control group received 3 mg/kg lidocaine 2% w/v diluted with saline to a total volume of 40 ml, and the midazolam group received an additional 50 μg/kg midazolam. Sensory and motor block onset and recovery times, tourniquet pain, intraoperative analgesic requirements, sedation, and anesthesia quality were recorded. Postoperative pain and sedation scores, time to first analgesic requirements, analgesic use in the first 24 h, and side effects were noted., Results: Sensory and motor block onset and recovery times did not differ significantly between groups. Tourniquet pain scores were lower at 10, 15, 20, and 30 min (P < 0.0001) in the midazolam group. Three (15%) patients in the midazolam group required fentanyl for tourniquet pain compared with thirteen (65%) patients in the control group (P = 0.02). Patients in both groups received fentanyl once. Midazolam group showed that significantly less patients required diclofenac for postoperative analgesia (P < 0.01) and analgesic-free period during first postoperative 24 h was significantly longer (726.8 ± 662.8 min vs. 91.0 ± 35.9 min, P < 0.0001). Postoperative pain scores were lower (P < 0.0001) and sedation scores higher (P < 0.05) for the first 2 h in the midazolam group., Conclusion: Addition of midazolam to lidocaine for IVRA improves anesthesia quality and enhances intraoperative and postoperative analgesia without causing side effects.

Background: Post kala-azar dermal leishmaniasis (PKDL) is a cutaneous form of disease that develops at variable times after individuals have received treatment for clinical visceral leishmaniasis (VL). The study aimed to investigate the possible role of interleukin 10 (IL-10) and development of PKDL., Methods: 77 families composed of 41 complete case-parent trios and 36 case-parent pairs from the Masalit ethnic group were genotyped for 3 IL10 promoter polymorphisms: -1082A/G, -819C/T and -592C/A., Results: Single point analysis using the transmission disequilibrium test showed no evidence of association between any of these IL10 promoter single nucleotide polymorphisms (SNPs) and development of PKDL. Haplotype analysis performed using TRANSMIT showed borderline significance between PKDL and the haplotype AA across -592C/A and -1082A/G (p = 0.053). Haplotypes GCC (0.33) and ATA (0.30) were the common haplotypes in this Sudanese population. Allele frequencies for the 3 SNPs differed significantly in Sudan compared to other African (Gambian, Malawian, YRI) populations., Conclusion: There is no evidence for an association between 3 SNPs in the IL10 gene promoter and susceptibility to PKDL in the Masalit ethnic group in Sudan, although some evidence for haplotype association was observed.

Background and Objective: The aim of this study was to evaluate the effect of ondansetron when added to lidocaine for intravenous regional anaesthesia (IVRA)., Methods: Thirty patients undergoing hand surgery were randomly assigned to two groups. IVRA was achieved with 3 mg kg lidocaine 2% w/v diluted with saline to a total volume of 40 ml in the control group or with 4 mg ondansetron 2 mg ml plus 3 mg kg lidocaine 2% w/v diluted with saline to a total volume of 40 ml in the ondansetron group. Sensory and motor block onset and recovery times, tourniquet pain score according to a visual analogue scale (VAS), intraoperative analgesic requirements and anaesthesia quality were recorded. Postoperative VAS pain score, time to first analgesic requirements and total diclofenac consumption in the first 24 h were noted., Results: Onset times were slightly but significantly shorter [1.4 min (95% confidence interval (CI) 0.5-2.3) and 1.5 min (95% CI 0.45-2.55)] and recovery times were slightly but significantly prolonged [2.6 min (95% CI 1.66-3.54) and 2.8 min (95% CI 1.83-3.78)] in patients receiving ondansetron. Tourniquet pain scores according to the VAS were slightly but significantly lower at 10, 15, 20 and 30 min, the time to intraoperative analgesic rescue was prolonged (35.0 +/- 7.1 min vs. 18.9 +/- 8.9 min, P = 0.043), a significantly lower number of patients (2 vs. 9) required additional analgesic and significantly less supplemental fentanyl was given [0 microg (0-0) vs. 59 microg (0-76), P = 0.015] in the ondansetron group. First intake of analgesic intake was longer (172 +/- 51 vs. 85 +/- 35 min, P = 0.0001), number of patients (7 vs. 15) requiring postoperative diclofenac was significantly lower and diclofenac requirements [0 mg (0-75) vs. 75 mg (75-150), P = 0.002) was significantly lower in the ondansetron group. Postoperative VAS scores were lower for the first 4 h in the ondansetron group., Conclusion: Addition of ondansetron to lidocaine may improve the quality of IVRA and prolong postoperative analgesia in patients undergoing hand surgery.

Purpose: Both magnesium and morphine provide enhanced patient analgesia after arthroscopic knee surgery when administered separately via the intra-articular route. Magnesium sulfate amplifies the analgesic effect of morphine. This study was designed to compare the analgesic effects of intra-articular magnesium and morphine, with bupivacaine, when used separately and in combination., Methods: Eighty patients undergoing arthroscopic menisectomy were randomized blindly into four intra-articular groups: group B+Mor+Mg received 20 ml 0.25% bupivacaine, morphine 2 mg, and magnesium 150 mg; group B+Mor received 20 ml 0.25% bupivacaine and morphine 2 mg; group B+Mg received 20 ml 0.25% bupivacaine and magnesium 150 mg; and group B received 20 ml 0.25% bupivacaine. Pain scores at rest and during movement, analgesic duration, and total analgesic consumption were recorded., Results: Group B+Mor and group B+Mg patients had equally effective postoperative analgesia. Group B+Mor+Mg patients had significantly reduced visual analogue scale (VAS) values both at rest and during movement and significantly increased time to first postoperative analgesic request, as well as significantly reduced total analgesic consumption, compared with the other groups., Conclusion: Intra-articular administration of magnesium sulfate or morphine, with bupivacaine, had comparable analgesic effects in the doses used. Their combination provided more effective postoperative analgesia than either drug alone.

A bioassay-guided fractionation of Juniperus procera berries yielded antiparasitic, nematicidal and antifouling constituents, including a wide range of known abietane, pimarane and labdane diterpenes. Among these, abieta-7,13-diene (1) demonstrated in vitro antimalarial activity against Plasmodium falciparum D6 and W2 strains (IC(50) = 1.9 and 2.0 microg/mL, respectively), while totarol (6), ferruginol (7) and 7beta-hydroxyabieta-8,13-diene-11,12-dione (8) inhibited Leishmania donovani promastigotes with IC(50) values of 3.5-4.6 microg/mL. In addition, totarol demonstrated nematicidal and antifouling activities against Caenorhabditis elegans and Artemia salina at a concentration of 80 microg/mL and 1 microg/mL, respectively. The resinous exudate of J. virginiana afforded known antibacterial E-communic acid (4) and 4-epi-abietic acid (5), while the volatile oil from its trunk wood revealed large quantities of cedrol (9). Using GC/MS, the two known abietanes totarol (6) and ferruginol (7) were identified from the berries of J. procera, J. excelsa and J. phoenicea., ((c) 2008 John Wiley & Sons, Ltd.)

Background: This prospective, randomized, double-blind study was designed to evaluate the preemptive and preventive analgesic efficacy of adding magnesium to a multimodal regimen of patient-controlled epidural analgesia (PCEA) in patients undergoing abdominal hysterectomy., Methods: Ninety patients were randomly assigned to one of the three groups. Pre-magnesium patients received bolus of magnesium 50 mg epidurally before induction of anaesthesia followed by infusion of 10 mg h(-1) until end of surgery. Post-magnesium patients received epidural saline during the same time periods plus bolus epidural magnesium 50 mg at the end of surgery. Patients in the control group received epidural saline during all three periods. Patients in the magnesium groups received PCEA with fentanyl 1 microg ml(-1), bupivacaine 0.08%, and magnesium 1 mg ml(-1) after operation. Patients in the control group received PCEA with fentanyl 1 microg ml(-1) and bupivacaine 0.08%. Data were recorded for three postoperative days., Results: There were significantly lower pain scores on rest or movement in the pre-magnesium group compared with the post-magnesium and control groups (P<0.05). The daily analgesic consumption in the pre-magnesium group was significantly less than the other two groups (P<0.05) and the dose consumed in the post-magnesium group was significantly smaller than the control group (P<0.05). The groups were similar with respect to haemodynamic and respiratory variables, sedation, pruritus, nausea, and vomiting., Conclusions: Continuous epidural magnesium started before anaesthesia provided preemptive, preventive analgesia, and an analgesic-sparing effect that improved postoperative analgesia without increasing the incidence of side-effects.

Several studies have reported on similar in vitro cellular responses to different malaria-antigen preparations in both malaria-primed and un-primed donors. Whether intact live parasites can exert a distinct type of response in either of the two groups is not well known. In this study, we developed a simple three-step centrifugation method for simultaneous enrichment of early and late blood stages from Plasmodium falciparum cultures. Such enriched P. falciparum fractions and other antigen preparations were used to stimulate lymphocytes from malaria-exposed and non-exposed individuals to examine the proliferative activity and expansion of CD3+, gammadelta+, CD4+, and CD8+ T cells. While lymphocytes from malaria non-exposed donors proliferated relatively higher than those from malaria-exposed donors in response to most antigens tested, the enriched fractions of live parasites exerted higher proliferative responses on cells from the latter donors. This suggests the existence of memory cells in the malaria-exposed donors, but not in the non-exposed ones. Flow cytometric analysis revealed a higher percentage expansion of CD4+ T cells in the responding cells of the exposed donors than the non-exposed ones. Taken together, this study reports on a simple method that simultaneously enriches for intact live early and late blood stages of P. falciparum parasites. Moreover, the study revealed higher expansion CD4+ T cells in the exposed individuals than the non-exposed in response to live malaria parasites and not to other parasite-antigen preparations.

The well-established relative resistance to malaria observed in the Fulani as compared with other sympatric tribes in West Africa has been attributed to their higher levels of serum immunoglobulin (Ig) G antibodies to malarial antigens. In this study, we confirm and extend the previous findings by analyses of the levels of IgM, IgG and IgG subclasses of anti-malarial antibodies in asymptomatic individuals of different sympatric tribes in Burkina Faso (Fulani/Mossi) and Mali (Fulani/Dogon). The Fulani showed significantly higher median concentrations of anti-malarial IgG and IgM antibodies than the sympatric tribes at both locations. Although the overall subclass pattern of antibodies did not differ between the tribes, with IgG1 and IgG3 as dominant, the Fulani showed consistently significantly higher levels of these subclasses as compared with those of the non-Fulani individuals. No significant differences were seen in the levels of total IgG between the tribes, but the Fulani showed significantly higher levels of total IgM than their neighbours in both countries. While the antibody levels to some nonmalarial antigens showed the same pattern of differences seen for antibody levels to malaria antigens, no significant such differences were seen with antibodies to other nonmalarial antigens. In conclusion, our results show that the Fulani in two different countries show higher levels of anti-malarial antibodies than sympatric tribes, and this appears not to be a reflection of a general hyper-reactivity in the Fulani.

The synergistic activity of antimycobacterial constituents from Saudi plants was evaluated in combination with isonicotinic acid hydrazide (INH) against four atypical organisms, namely, Mycobacterium intracellulare, M. smegmatis, M. xenopei and M. chelonei. The potency of INH was increased four-fold, using an in vitro checkerboard method, against each mycobacteria when tested with a subtoxic concentration of the totarol, isolated from J. procera. The MIC values of totarol, ferulenol (from Ferula communis) and plumbagin (from Plumbago zeylanica) were thus lowered from 1.25-2.5 to 0.15-0.3 microg/mL due to synergism with INH. When tested against the resistant strain of M. tuberculosis H37Rv, plumbagin and 7beta-hydroxyabieta-8,13-dien-11,12-dione exhibited inhibitory activity at <12.5 microg/mL, while others were inactive at this concentration., (Copyright 2004 John Wiley & Sons, Ltd.)

A fluorometric microplate assay was performed for the detection of respiratory burst activity in a human leukaemia cell line HL-60 by assessing oxidation of 2',7'-dichloro fluorescin diacetate (DCFH-DA). This method is based on the detection of DCFH oxidation due to the presence of hydrogen peroxide. In the present study, the antioxidant activity of a number of structurally related flavonoids of plant origin and some of their microbial transformation products (1-18) were evaluated., (Copyright 2003 John Wiley & Sons, Ltd.)

The natural and semi-synthetic analogs of substituted 1,4-benzoquinones were evaluated for in vitro cytotoxic and antioxidant activities. Maesanin, dihydromaesanin, maesanin dimethyl ether and isomeric mixtures of 3-[(Z)-10'-pentadecenyl]-benzoquinone derivatives exhibited cytotoxic activity against HL-60 cell line (IC50 values 4.5, 2.2, 0.43 and 2.8 microg/mL, respectively), while it was found to be inactive against ROS (Reactive Oxygen Species) generation in HL-60. In contrast, the isomeric acylated benzoquinones with shorter alkyl substituents, namely, 2-acetoxy-5-hydoxy-6-methyl-3-tridecyl-1,4-benzoquinone and 2-hydoxy-5-acetoxy-6-methyl-3-tridecyl-1,4-benzoquinone showed most prominent antioxidant and antiproliferative effect on HL-60 (IC50 values 6.2 and 2.2 microg/mL, respectively), as well as cytotoxicities against SK-MEL, KB, BT-549 and SK-OV-3 carcinomas (IC50 values <1.1-4.2 microg/mL). All benzoquinones were found to be inactive against cell aggregation and cell adhesion assays, thus showing no effect on immune responses and inflammation., (Copyright 2003 John Wiley & Sons, Ltd.)

Clutia richardiana L. is a traditional medicinal herb with demonstrated hypoglycemic effects. An HPLC method (Luna((R)) C(18) column, gradient elution, UV detection at 220 nm) has been utilized to determine the levels of the major diterpenes of C. richardiana in extracts obtained by using three different solvents. Extraction with the organic solvents methanol and acetonitrile was more efficient than aqueous extraction with hot water, but nine markers could be detected equally in all extracts. The aqueous extract was non-toxic against a number of human cell lines, which is a promising indication for its use as a safe and effective antidiabetic herbal preparation., (Copyright 2003 John Wiley & Sons, Ltd.)

The aerial parts of Centaurothamnus maximus yielded three cytotoxic guaianolides, chlorojanerin (1), cynaropicrin (2) and janerin (3). The structure elucidation of 1-3 was based on (1)H and (13)C NMR data, mainly 2D-NMR (1)H-(1)H COSY and (1)H-(13)C HETCOR experiments. Compounds 1-3 showed in vitro cytotoxic activity against human cancer cell lines of malignant melanoma (SK-MEL), epidermoid (KB), ductal (BT-549) and ovarian (SK-OV-3) carcinomas with IC(50) values of 2-6 microgram/mL. In addition, 12 sesquiterpene lactones (4-15), isolated previously from the aerial parts of Vicoa pentanema, were evaluated for cytotoxic and antimicrobial activities. 2alpha- Acetoxy-3beta-hydroxyalantolactone (10) and 8beta-hydroxyparthenolide (14) were found to be the main cytotoxic agents (IC(50) values of 2-6 microgram/mL against SK-MEL, BT-549 and SK-OV-3), while lactones 4, 5, 11 and 15 selectively inhibited the growth of human malignant melanoma (IC(50) value of 3.6-7.3 microgram/mL). Cell aggregation and cell adhesion assays, using HL-60 and HeLa cell lines, evaluated the effect of cytotoxic constituents 1-3, 10 and 14 on immune response and inflammation., (Copyright 2003 John Wiley & Sons, Ltd.)

The aerial parts of Teucrium oliverianum yielded two neo-clerodane diterpenoids, teucrolin F and G, together with the known teucrolin E. The previously proposed structure for teucrolin E was revised so that it contains a tetrahydrofuran ring instead of an oxetane ring. This was based on analysis of the NMR spectroscopic data of its diacetate, including its NOE spectra. In addition, the structural assignments of the new diterpenoids were based on 1H and 13C NMR spectroscopic studies, mainly 2D NMR experiments, including homonuclear and heteronuclear correlations.

Photooxygenation of anhydrodeoxydihydroartemisinin (4) followed by chromatographic separation of the reaction mixture yielded the new compounds alpha- (5) and beta-hydroperoxydeoxyartemisitene (8) and the formate ester 7, together with two previously reported compounds, 6 and 9. Reduction of 5 using polymer-bound triphenylphosphine afforded the new compound dihydrodeoxyartemisitene (10). Treatment of 10 with a catalytic amount of BF(3)-OEt(2) yielded the C(2)-symmetrical dimer bis(dihydrodeoxyartemisitene) ether (11) and two new compounds, dihydrodeoxyartemisitene methyl ether (12) and the dimer 13, as minor products. Dehydroacetoxylation of 5 using acetic anhydride in pyridine afforded deoxyartemisitene (14). The identities of the new compounds (5, 7, 8, 10-14) were deduced from their spectral data and by chemical derivatization. The stereochemistry of dimer 11 was defined on the basis of X-ray crystallographic analysis. All compounds were evaluated in vitro in the National Cancer Institute drug-screening program consisting of 60 human cancer cell lines derived from nine different tissues. Of the compounds tested, deoxyartemisitene (14) demonstrated significant cytotoxicity against a number of human cancer cell lines.

Tuberculosis and malaria remain the leading causes of mortality among human infectious diseases in the world. It is estimated that 3 to 5 million people die from tuberculosis and malaria each year. Although it is traditionally believed that CD4 and CD8 alphabeta T lymphocytes are mandatory for protective immune responses against Mycobacterium tuberculosis and Plasmodium falciparum (the ethiologic agents of tuberculosis and the most severe form of malaria, respectively), there is still incomplete understanding of the mechanisms of immune protection and of the causes of its failure in the affected patients. Several studies in humans and animal models have suggested that Vgamma9/Vdelta2 T cells may play an important role in the immune responses against Mycobacterium tuberculosis and Plasmodium falciparum. Vgamma9/Vdelta2 T cells represent about 75% of all circulating gammadelta T cells while they can be greatly expanded during the acute phase of Mycobacterium tuberculosis and Plasmodium falciparum malaria. Vgamma9/Vdelta2 T recognize a new class of antigenic molecules which are nonpeptidic in nature and contain critical phosphate moieties (phosphoantigens). Interestingly, phosphoantigens isolated from Mycobacterium tuberculosis and Plasmodium falciparum share strong structural homology and are probably identical. However, despite a large body of data reported in the literature, it is not yet clear whether Vgamma9/Vdelta2 T cells play a protective or pathogenic role in immune responses against Mycobacterium tuberculosis and Plasmodium falciparum. In this review we summarize our current knowledge of the biology of Vgamma9/Vdelta2 T cells in response to the two pathogens, Mycobacterium tuberculosis and Plasmodium falciparum, and provide evidence suggesting definition of a novel and important protective role through which Vgamma9/Vdelta2 T cells can contribute to the killing of microorganisms residing in intracellular compartments.