Pregnancy is rare among breastfeeding women with lactational amenorrhoea. The lactational amenorrhoea method (LAM) is the informed use of breastfeeding as a contraceptive method by a woman who is still amenorrhoeic, and who is not feeding her baby with supplements, for up to 6 months after delivery. Under these three conditions, LAM users are thought to have 98% protection from pregnancy. It can be difficult, however, to determine when supplementation of the baby's diet begins. We have analysed data from nine studies of the recovery of fertility in breastfeeding women to assess the effectiveness of lactational amenorrhoea alone, irrespective of whether supplements have been introduced, as a fertility regulation method post partum. Cumulative probabilities of ovulation during lactational amenorrhoea were 30.9 and 67.3 per 100 women at 6 and 12 months, respectively, compared with 27.2 at 6 months when all three criteria of the LAM were met. Cumulative pregnancy rates during lactational amenorrhoea were 2.9 and 5.9 per 100 women at 6 and 12 months, compared with 0.7 at 6 months for the LAM. The probability of pregnancy during lactational amenorrhoea calculated from these studies is similar to that of other modern contraceptive methods, and it seems reasonable for a woman to rely on lactational amenorrhoea without regard to whether she is fully or partly breastfeeding. So that amenorrhoea and fertility suppression can be maintained, counselling about good breastfeeding and weaning practices remains important.

Moringa (Moringa oleifera Lam.) is an edible plant used as both a food and medicine throughout the tropics. A moringa concentrate (MC), made by extracting fresh leaves with water, utilized naturally occurring myrosinase to convert four moringa glucosinolates into moringa isothiocyanates. Optimum conditions maximizing MC yield, 4-[(α-L-rhamnosyloxy)benzyl]isothiocyanate, and 4-[(4'-O-acetyl-α-L-rhamnosyloxy)benzyl]isothiocyanate content were established (1:5 fresh leaf weight to water ratio at room temperature). The optimized MC contained 1.66% isothiocyanates and 3.82% total polyphenols. 4-[(4'-O-acetyl-α-L-rhamnosyloxy)benzyl]isothiocyanate exhibited 80% stability at 37°C for 30 days. MC, and both of the isothiocyanates described above significantly decreased gene expression and production of inflammatory markers in RAW macrophages. Specifically, both attenuated expression of iNOS and IL-1β and production of nitric oxide and TNFα at 1 and 5 μM. These results suggest a potential for stable and concentrated moringa isothiocyanates, delivered in MC as a food-grade product, to alleviate low-grade inflammation associated with chronic diseases.

BACKGROUND

The common or brinjal eggplant (Solanum melongena L.) belongs to the Leptostemonum Clade (the "spiny" solanums) of the species-rich genus Solanum (Solanaceae). Unlike most of the genus, the eggplant and its relatives are from the Old World; most eggplant wild relatives are from Africa. An informal system for naming eggplant wild relatives largely based on crossing and other biosystematics data has been in use for approximately a decade. This system recognises several forms of two broadly conceived species, S. incanum L. and S. melongena. Recent morphological and molecular work has shown that species-level differences exist between these entities, and a new species-level nomenclature has been identified as necessary for plant breeders and for the maintenance of accurately named germplasm.

RESULTS

We examined herbarium specimens from throughout the wild species ranges as part of a larger revision of the spiny solanums of Africa. Based on these morphological and molecular studies, we delimited species in the group to which the common eggplant belongs and constructed identification keys for the group. We also examined the monophyly of the group considered as the eggplant relatives by previous authors.

CONCLUSIONS

WE RECOGNISE TEN SPECIES IN THIS GROUP: S. aureitomentosum Bitter, S. campylacanthum A.Rich., S. cerasiferum Dunal, S. incanum L., S. insanum L., S. lichtensteinii Willd., S. linnaeanum Hepper & P.-M.L.Jaeger, S. melongena L., S. rigidum Lam. and S. umtuma Voronts. & S.Knapp. We review the history of naming and provide keys and character lists for all species. Ploidy level differences have not been investigated in the eggplant wild relatives; we identify this as a priority for improvement of crop wild relative use in breeding. The application of species-level names to these entities will help focus new collecting efforts for brinjal eggplant improvement and help facilitate information exchange.

Rheumatoid arthritis (RA) is an autoimmune and chronic inflammatory disease that leads to pannus formation followed by severe joint destruction, characterized by synovial hyperplasia, inflammation and angiogenesis. Swertiamarin is a secoiridoid glycoside that is used as an anti-inflammatory compound, mainly found in Enicostema axillare (Lam) A. Raynal, a medicinal plant used in Indian system of traditional medicine. In the present study, the effect of swertiamarin was evlauated in experimental adjuvant arthritis animal model by the estimation of biochemical (paw thickness, lysosomal enzymes, and urinary degradative products) parameters, proinflammatory cytokines and enzymes along with histopathological and radiographic observations. The proteins of phosphorylated NF-κB/IκB and JAK2/STAT3 transcription factors were also quantified from experimental animals as well as LPS induced RAW 264.7 macrophage cells. In in silico analysis, swertiamarin was docked with proinflammatory enzymes to confirm its potential. The administration of swertiamarin (2, 5, 10mg/kg bw) significantly (P⩽0.05) inhibited the levels of paw thickness, lysosomal enzymes and increased the body weight of experimental animals in a dose dependent manner. In molecular analysis, the treatment decreased the release of proinflammatory cytokines (IL1, TNF, IL-6) and proangiogenic enzymes (MMPs, iNOS, PGE2, PPARγ and COX-2); and also significantly (P⩽0.05) increased the levels of antiinflammatory proteins (IL-10, IL-4) when compared to the disease groups. The swertiamarin treatment significantly (P⩽0.05) inhibited the release of NF-κB p65, p-IκBα, p-JAK2 and p-STAT3 signaling proteins levels on both experimental animals and LPS induced cells. Histopathological and radiological analysis evidenced the curative effect of swertiamarin on bone destruction. The docking studies of swertiamarin on proinflammatory enzymes supported the results from the in vivo experiments. Thus the swertiamarin inhibited the development of arthritis by modulating NF-κB/IκB and JAK2/STAT3 signaling. These findings suggested that swertiamarin acted as an anti-rheumatic agent.

We examined alternative and classical complement activation induced by whole bacilli of Mycobacterium bovis BCG and Mycobacterium tuberculosis products. After exposure to BCG, there were higher levels of the terminal complement complex in sera from Indian tuberculosis patients than in sera from healthy controls. The addition of BCG with or without EGTA to these sera indicated that approximately 70 to 85% of the total levels of the terminal complement complex was formed by classical activation. Sera from Indian tuberculosis patients contained more antibody to lipoarabinomannan (LAM) than sera from healthy Indians. Levels of anti-LAM immunoglobulin G2 (IgG2), but not anti-LAM IgM, correlated positively with classical activation induced by BCG in the sera. By flow cytometry, deposition of C3 and terminal complement complex on bacilli incubated with normal human serum was demonstrated. The anticomplement staining was significantly reduced in the presence of EGTA and EDTA. Flow cytometry also revealed the binding of complement to BCG incubated with rabbit anti-LAM and then with factor B-depleted serum. This indicates that classical activation plays a major role in complement activation induced by mycobacteria and that anti-LAM IgG on the bacilli can mediate this response. Classical complement activation may be important for the extent of phagocytosis of M. tuberculosis by mononuclear phagocytes, which may influence the course after infection.

OBJECTIVE

The leaves and root of Toddalia asiatica (L.) Lam. (Rutaceae) are widely used as a folk medicine in India. Hexane, chloroform, ethyl acetate, methanol and water extracts of Toddalia asiatica leaves and isolated compound Flindersine were tested against bacteria and fungi.

METHODS

Antibacterial and antifungal activities were tested against bacteria and fungi using disc-diffusion method and minimum inhibitory concentrations (MICs). The compound was confirmed using X-ray crystallography technique.

RESULTS

Antibacterial and antifungal activities were observed in ethyl acetate extract. One active principle Flindersine (2,6-dihydro-2,2-dimethyl-5H-pyrano [3,2-c] quinoline-5-one-9cl) was isolated from the ethyl acetate extract. The MIC values of the compound against bacteria Bacillus subtilis (31.25 microg/ml), Staphylococcus aureus (62.5 microg/ml), Staphylococcus epidermidis (62.5 microg/ml), Enterococcus faecalis (31.25 microg/ml), Pseudomonas aeruginosa (250 microg/ml), Acinetobacter baumannii (125 microg/ml) and fungi Trichophyton rubrum 57 (62.5 microg/ml), Trichophyton mentagrophytes (62.5 microg/ml), Trichophyton simii (62.5 microg/ml), Epidermophyton floccosum (62.5 microg/ml), Magnaporthe grisea (250 microg/ml) and Candida albicans (250 microg/ml) were determined.

CONCLUSIONS

Ethyl acetate extract showed promising antibacterial and antifungal activity and isolated compound Flindersine showed moderate activity against bacteria and fungi.

BACKGROUND

Moringa oleifera Lam. (Moringaceae) is a rich source of essential minerals and antioxidants; it has been used in human and animal nutrition. The leaves and flowers are being used by the population with great dietary importance.

OBJECTIVE

The present study was to investigate the therapeutic effects of the hydroethanolic extract of Moringa oleifera (MO) leaves and flowers against hepatotoxicity induced by acetaminophen (APAP) in rats.

METHODS

In the hepatoprotective study, either flowers or leaves of hydroethanolic extract (200 or 400 mg/kg bw through IP injection) were administered an hour after APAP administration. N-Acetylcysteine (NAC) was used as the positive control for this study. Liver and kidney function tests including lipid peroxidation levels were analyzed and histopathological changes of liver and kidney were also observed.

RESULTS

Acetaminophen-induced hepatotoxicity increased the activities of liver marker enzymes. Histologically, the liver was observed to have inflammation and bridging necrosis. Liver marker enzymes were significantly reduced when treated with flower and leaf extracts of MO in animals with APAP induced toxicity. In addition, there were no significant changes observed in clinical markers of kidney function. Histological observation on liver tissue from the rats treated with MO flower and leaf extract showed reduction in the severity of the liver damage.

CONCLUSIONS

These results indicated the possible therapeutic action of flower and leaf extract from MO in protecting liver damage in rats given an over dosage of APAP.

TB is the leading cause of HIV/AIDS-related deaths globally. New diagnostic tools are urgently needed to avert deaths from undiagnosed HIV-associated TB. Although simple assays that detect lipoarabinomannan (LAM) in urine have been commercially available for years, their specific role and utility were initially misunderstood, such that they have been slower to emerge from the diagnostics pipeline than otherwise might have been expected. In this article, we review and explain how urine-LAM assays should be understood as diagnostics for disseminated TB in HIV-positive patients with advanced immunodeficiency, in whom haematogenous TB dissemination to the kidneys serves as the primary mechanism by which LAM enters the urine. These insights are critical for the appropriate design of studies to evaluate these assays and to understand how they might be most usefully implemented. This understanding also supports the 2015 WHO recommendations on the restricted use of these assays in sick HIV-positive patients with advanced immunodeficiency.

OBJECTIVE

Friedelin was isolated from Azima tetracantha Lam. leaves collected from Kallakurichi, Villuppuram district, Tamil Nadu, India. The anti-inflammatory, analgesic and antipyretic activities of friedelin have been investigated in Wistar rats and mice.

METHODS

Friedelin was isolated from the hexane extract of leaves of A. tetracantha using column chromatography. The effects of friedelin on inflammation were studied by using carrageenan-induced hind paw oedema, croton oil-induced ear oedema, acetic acid-induced vascular permeability, cotton pellet-induced granuloma and adjuvant-induced arthritis. The analgesic effect of friedelin was evaluated using the acetic acid-induced abdominal constriction response, formalin-induced paw licking response and the hot-plate test. The antipyretic effect of friedelin was evaluated using the yeast-induced hyperthermia test in rats.

RESULTS

In the acute phase of inflammation, maximum inhibitions of 52.5 and 68.7% (P<0.05) were noted with 40 mg/kg friedelin in carrageenan-induced paw oedema and croton oil-induced ear oedema, respectively. Administration of friedelin (40 mg/kg) significantly (P<0.05) decreased the formation of granuloma tissue induced by cotton pellet at a rate of 36.3%. In the adjuvant-induced arthritis test friedelin inhibited 54.5% of paw thickness. Friedelin inhibited acetic acid-induced vascular permeability in mice. Friedelin also produced significant (P<0.05) analgesic activity in the acetic acid-induced abdominal constriction response and formalin-induced paw licking response. In the hot-plate test, friedelin did not show any significant results when compared with control. Treatment with friedelin showed a significant (P<0.05) dose-dependent reduction in pyrexia in rats.

CONCLUSIONS

The results suggested that friedelin possessed potent anti-inflammatory, analgesic and antipyretic activities.

BACKGROUND

Mozambique is one of the countries with the highest burden of tuberculosis (TB) in Sub-Saharan Africa, and information on the predominant genotypes of Mycobacterium tuberculosis circulating in the country are important to better understand the epidemic. This study determined the predominant strain lineages that cause TB in Mozambique.

RESULTS

A total of 445 M. tuberculosis isolates from seven different provinces of Mozambique were characterized by spoligotyping and resulting profiles were compared with the international spoligotyping database SITVIT2.The four most predominant lineages observed were: the Latin-American Mediterranean (LAM, n = 165 or 37%); the East African-Indian (EAI, n = 132 or 29.7%); an evolutionary recent but yet ill-defined T clade, (n = 52 or 11.6%); and the globally-emerging Beijing clone, (n = 31 or 7%). A high spoligotype diversity was found for the EAI, LAM and T lineages.

CONCLUSIONS

The TB epidemic in Mozambique is caused by a wide diversity of spoligotypes with predominance of LAM, EAI, T and Beijing lineages.

OBJECTIVE

Nine plants from Reunion Island, selected using ethnopharmacology and chemotaxonomy, were investigated for their potential antimalarial value.

METHODS

Thirty-eight extracts were prepared by maceration using CH(2)Cl(2) and MeOH, and were tested for in vitro activity against the 3D7 and W2 strain of Plasmodium falciparum. The most active extracts were then tested for in vitro cytotoxicity on human WI-38 fibroblasts to determine the selectivity index. Those extracts were also investigated in vivo against Plasmodium berghei infected mice.

RESULTS

Most active of the extracts tested were the dichloromethane leaves extracts of Nuxia verticillata Lam. (Buddlejaceae), Psiadia arguta Voigt. (Asteraceae), Lantana camara L. (Verbenaceae), the methanol extracts from Aphloia theiformis (Vahl) Benn. (Aphloiaceae) bark, and Terminalia bentzoe L. (Combretaceae) leaves displaying in vitro IC(50) values ranging from 5.7 to 14.1mug/ml. Extracts from Psiadia, Aphloia at 200mg/(kgday) and Teminalia at 50mg/(kgday) also exhibited significant (p<0.0005) parasite inhibition in mice: 75.5%, 65.6% and 83.5%, respectively.

CONCLUSIONS

Two plants showed interesting antimalarial activity with good selectivity: Aphloia theiformis and Terminalia bentzoe. Nuxia verticillata still needs to be tested in vivo, with a new batch of plant material.

Protoplasts of 6-azauracil (AU) resistant cell lines of Solanum melongena L. were fused with protoplasts of S. sisymbriifolium Lam. to create somatic hybrids between these sexually-incompatible species. Following fusion, colonies were selected which were capable of growth in medium containing 1mM AU. These colonies were placed on medium containing zeatin which had been shown to stimulate anthocyanin production during shoot organogenesis in tissue explants of S. sisymbriifolium but not in S. melongena. A total of 37 anthocyanin-producing colonies were identified from which 26 hybrid plants were regenerated. The morphological traits intermediate to those of the parents included: flower colour, leaf shape, and trichome density. Cytogenetic analysis revealed that all hybrids were aneuploids but their chromosome numbers were close to the expected number of 48. Isozyme analysis revealed that nuclear genes of both parents were expressed in the hybrids. In addition, isoelectric focussing of the large subunit of ribulose 1,5-bisphosphate carboxylase (Rubisco) provided evidence that each hybrid expressed only the S. sisymbriifolium chloroplast genome. All hybrids regenerated thus far have been sterile.

Lymphangioleiomyomatosis (LAM), a systemic disorder affecting almost exclusively young women, is characterized by the abnormal proliferation of smooth muscle-like cells (LAM cells). LAM can occur either in association with the tuberous sclerosis complex (TSC) (TSC-LAM) or without TSC (sporadic LAM). Recent studies have demonstrated that LAM is a neoplasm arising from constitutive activation of the mammalian target of rapamycin signaling pathway dysregulated by a functional loss of TSC genes, but the primary organ of origin remains unclear. Therefore, we performed histologic and immunohistologic analyses of gynecologic organs in 20 patients, half with and the other half without pulmonary LAM, to determine how often LAM involves the uterus. The results showed that 9 of 10 (90%) patients with pulmonary LAM had uterine LAM lesions. In contrast, no patients without pulmonary LAM had so. All uterine LAM lesions were accompanied by LAM lesions in retroperitoneal or pelvic lymph nodes and LAM cell clusters, each enveloped by a monolayer of vascular endothelial growth factor receptor-3-positive lymphatic endothelial cells. Furthermore, when we compared uterine lesions of TSC-LAM with those of sporadic LAM, proliferation of HMB45-positive epithelioid-shaped LAM cells and infiltrates with a tongue-like growth pattern was more prominent in the former, whereas the extent of lymphangiogenesis within the myometrium was greater in the latter. These results indicate that uterine involvement is a common manifestation of LAM, and, possibly, that the uterus or an adjacent locale in the retroperitoneum or pelvic cavity is the primary site of origin of LAM.

BACKGROUND

In Africa, tuberculous meningitis (TBM) is an important opportunistic infection in HIV-positive patients. Current diagnostic tools for TBM perform sub-optimally. In particular, the rapid diagnosis of TBM is challenging because smear microscopy has a low yield and PCR is not widely available in resource-poor settings.

METHODS

We evaluated the performance outcome of a novel standardized lipoarabinomannan (LAM) antigen-detection assay, using archived cerebrospinal fluid samples, in 50 African TBM suspects of whom 68% were HIV-positive.

RESULTS

Of the 50 participants 14, 23 and 13 patients had definite, probable and non-TBM, respectively. In the non-TB group there were 5 HIV positive patients who were lost to follow-up and in whom concomitant infection with Mycobacterium tuberculosis could not be definitively excluded. The test sensitivities and specificities were as follows: LAM assay 64% and 69% (cut-point 0.22), smear microscopy 0% and 100% and PCR 93% and 77%, respectively.

CONCLUSIONS

In this preliminary proof-of-concept study, a rapid diagnosis of TBM could be achieved using LAM antigen detection. Although specificity was sub-optimal, the estimates provided here may be unreliable because of a classification bias inherent in the study design where it was not possible to exclude TBM in the presumed non-TBM cases owing to a lack of clinical follow-up. As PCR is largely unavailable, the LAM assay may well prove to be a useful adjunct for the rapid diagnosis of TBM in high HIV-incidence settings. These preliminary results justify further enquiry and prospective studies are now required to definitively establish the place of this technology for the diagnosis of TBM.

BACKGROUND

Rapid diagnostic tests are urgently needed to mitigate HIV-associated tuberculosis (TB) mortality. We evaluated diagnostic accuracy of the rapid urine lipoarabinomannan (LAM) test for pulmonary TB and assessed the effect of a two-sample strategy.

METHODS

HIV-infected adults eligible for antiretroviral therapy were prospectively enrolled from Korle-Bu Teaching Hospital in Ghana and followed for minimum 6 months. We applied the LAM test on urine collected as a spot and early morning sample. Diagnostic accuracy was analysed for a microbiological TB reference standard based on sputum culture and Gene Xpert MTB/RIF results and for a composite reference standard including clinical follow-up data. Performance of sputum smear microscopy was included for comparison.

RESULTS

Of 469 patients investigated for TB, the LAM test correctly identified 24/55 (44 %) of microbiologically confirmed TB cases. Sensitivity of the LAM test was positively associated with hospitalisation (67 %), Modified Early Warning Score>> 4 (57 %) and subsequent death (71 %). LAM test specificity was 95 % increasing to 98 % for the composite reference standard. A two-sample LAM test strategy did not improve test performance. Using concentrated sputum for Ziehl-Neelsen and fluorescence microscopy in combination yielded a sensitivity of 31/55 (56 %) that increased to 35/55 (64 %) when the LAM test was added. Surprisingly, nontuberculous mycobacteria were cultured in 34/469 (7 %) and associated with a positive LAM test (p = 0.008).

CONCLUSIONS

LAM test sensitivity was highest in patients with poor prognosis and subsequent death and did not increase with a two-sample strategy. A rigorous sputum microscopy strategy had superior sensitivity, but the simplicity of the LAM test holds operational possibilities as a TB screening method among severely sick patients.

The D-arabinan-containing polymers arabinogalactan (AG) and lipoarabinomannan (LAM) are essential components of the unique cell envelope of the pathogen Mycobacterium tuberculosis. Biosynthesis of AG and LAM involves a series of membrane-embedded arabinofuranosyl (Araf) transferases whose structures are largely uncharacterised, despite the fact that several of them are pharmacological targets of ethambutol, a frontline drug in tuberculosis therapy. Herein, we present the crystal structure of the C-terminal hydrophilic domain of the ethambutol-sensitive Araf transferase M. tuberculosis EmbC, which is essential for LAM synthesis. The structure of the C-terminal domain of EmbC (EmbC(CT)) encompasses two sub-domains of different folds, of which subdomain II shows distinct similarity to lectin-like carbohydrate-binding modules (CBM). Co-crystallisation with a cell wall-derived di-arabinoside acceptor analogue and structural comparison with ligand-bound CBMs suggest that EmbC(CT) contains two separate carbohydrate binding sites, associated with subdomains I and II, respectively. Single-residue substitution of conserved tryptophan residues (Trp868, Trp985) at these respective sites inhibited EmbC-catalysed extension of LAM. The same substitutions differentially abrogated binding of di- and penta-arabinofuranoside acceptor analogues to EmbC(CT), linking the loss of activity to compromised acceptor substrate binding, indicating the presence of two separate carbohydrate binding sites, and demonstrating that subdomain II indeed functions as a carbohydrate-binding module. This work provides the first step towards unravelling the structure and function of a GT-C-type glycosyltransferase that is essential in M. tuberculosis.

The modulatory effects of a hydro-alcoholic extract of drumsticks of Moringa oliefera Lam at doses of 125 mg/kg bodyweight and 250 mg/ kg body weight for 7 and 14 days, respectively, were investigated with reference to drug metabolising Phase I (Cytochrome b(5) and Cytochrome p(450) ) and Phase II (Glutathione-S- transferase) enzymes, anti-oxidant enzymes, glutathione content and lipid peroxidation in the liver of 6-8 week old female Swiss albino mice. Further, the chemopreventive efficacy of the extract was evaluated in a two stage model of 7,12 - dimethylbenz(a)anthracene induced skin papillomagenesis. Significant increase (p<0.05 to p<0.01) in the activities of hepatic cytochrome b(5), cytochrome p(450), catalase, glutathione peroxidase ( GPx ), glutathione reductase (GR), acid soluble sulfhydryl content (-SH ) and a significant decrease ( p<0.01 ) in the hepatic MDA level were observed at both dose levels of treatment when compared with the control values. Glutathione-S- transferase ( GST )activity was found to be significantly increased (p<0.01 ) only at the higher dose level. Butylated hydroxyanisol (BHA ) fed at a dose of 0.75% in the diet for 7 and 14 days (positive control ) caused a significant increase (p<0.05 to p<0.01) in the levels of hepatic phase I and phase II enzymes, anti- oxidant enzymes, glutathione content and a decrease in lipid peroxidation. The skin papillomagenesis studies demonstrated a significant decrease (p<0.05 ) in the percentage of mice with papillomas, average number of papillomas per mouse and papillomas per papilloma bearing mouse when the animals received a topical application of the extract at a dose of 5mg/ kg body weight in the peri-initiation phase 7 days before and 7 days after DMBA application, Group II ), promotional phase (from the day of croton oil application and continued till the end of the experiment, Group III ) and both peri and post initiation stages (from 7 days prior to DMBA application and continued till the end of the experiment, Group IV) compared to the control group (Group I ). The percentage inhibition of tumor multiplicity has been recorded to be 27, 72, and 81 in Groups II, III, and IV, respectively. These findings are suggestive of a possible chemopreventive potential of Moringa oliefera drumstick extract against chemical carcinogenesis.

OBJECTIVE

To evaluate morphology and integrity of the levator ani muscle (LAM) with three-dimensional ultrasound early in the postpartum period.

METHODS

Prospective cross-sectional observational study.

METHODS

University hospital in Germany.

METHODS

Women after vaginal delivery and caesarean section with no previous vaginal delivery.

METHODS

Three-dimensional perineal ultrasound was performed between 48 and 72 hours postpartum. The axial plane at the level of minimal hiatal dimension and tomographic ultrasound imaging were used to determine LAM biometry and defect.

METHODS

Primary outcome was to compare hiatal dimensions and levator defect following vaginal delivery or caesarean section. For secondary outcomes, we evaluated the role of caesarean section in protecting levator integrity, and the possible involvement of the first stage of labour in LAM changes.

RESULTS

In all, 157 women participated: 81 (51.6%) following vaginal delivery (70 spontaneous and 11 operative deliveries) and 76 (48.4%) following caesarean section (55 elective and 21 emergency caesarean sections). All biometric indices of the levator were higher after vaginal delivery (P<0.001), except for LAM thickness. LAM defects were found to be significantly associated with vaginal delivery, with relative risk 7.5 (P<0.001). Following vaginal delivery, 32 (39.5%) levator defects were found: 27 (38.5%) after spontaneous delivery and five (45.4%) after operative delivery. Four (5.2%) women had a levator defect following emergency caesarean section.

CONCLUSIONS

Vaginal delivery modifies and damages the LAM: the risk of levator defect after vaginal delivery is more than seven times higher than after caesarean section. Despite this, emergency caesarean section seems to have no complete preventive effect on LAM trauma.

BACKGROUND

The urine lipoarabinomannan (LAM) strip-test (Determine®-TB) can rapidly rule-in TB in HIV-infected persons with advanced immunosuppression. However, given high rates of empiric treatment amongst hospitalised patients in high-burden settings (≈ 50%) it is unclear whether LAM can add any value to clinical decision making, or identify a subset of patients with unfavourable outcomes that would otherwise have been missed by empiric treatment.

METHODS

281 HIV-infected hospitalised patients with suspected TB received urine LAM strip testing, and were categorised as definite (culture-positive), probable-, or non-TB. Both the proportion and morbidity of TB cases identified by LAM testing, early empiric treatment (initiated prior to test result availability) and a set of clinical predictors were compared across groups.

RESULTS

187/281 patients had either definite- (n = 116) or probable-TB (n = 71). As a rule-in test for definite and probable-TB, LAM identified a similar proportion of TB cases compared to early empiric treatment (85/187 vs. 93/187, p = 0.4), but a greater proportion than classified by a set of clinical predictors alone (19/187; p<0.001). Thirty-nine of the 187 (21%) LAM-positive patients who had either definite- or probable-TB were missed by early empiric treatment, and of these 25/39 (64%) would also have been missed by smear microscopy. Thus, 25/187 (8%) of definite- or probable-TB patients with otherwise delayed initiation of TB treatment could be detected by the LAM strip test. LAM-positive patients missed by early empiric treatment had a lower median CD4 count (p = 0.008), a higher median illness severity score (p = 0.001) and increased urea levels (p = 0.002) compared to LAM-negative patients given early empiric treatment.

CONCLUSIONS

LAM strip testing outperformed TB diagnosis based on clinical criteria but in day-to-day practice identified a similar proportion of patients compared to early empiric treatment. However, compared to empiric treatment, LAM identified a different subset of patients with more advanced immunosuppression and greater disease severity.

Lamellarin D (Lam D), a marine alkaloid, exhibits a potent cytotoxicity against many different tumors. The pro-apoptotic function of Lam D has been attributed to its direct induction of mitochondrial permeability transition (MPT). This study was undertaken to explore the mechanisms through which Lam D promotes changes in mitochondrial function and as a result apoptosis. The use of eight Lam derivatives provides useful structure-apoptosis relationships. We demonstrate that Lam D and structural analogues induce apoptosis of cancer cells by acting directly on mitochondria inducing reduction of mitochondrial membrane potential, swelling and cytochrome c release. Cyclosporin A, a well-known inhibitor of MPT, completely prevents mitochondrial signs of apoptosis. The drug decreases calcium uptake by mitochondria but not by microsomes indicating that Lam D-dependent permeability is specific to mitochondrial membranes. In addition, upon Lam D exposure, a rapid decline of mitochondrial respiration and ATP synthesis occurs in isolated mitochondria as well as in intact cells. Evaluation of the site of action of Lam D on the electron-transport chain revealed that the activity of respiratory chain complex III is reduced by a half. To determine whether Lam D could induce MPT-dependent apoptosis by inhibiting mitochondrial respiration, we generated respiration-deficient cells (rho0) derived from human melanoma cells. In comparison to parental cells, rho0 cells are totally resistant to the induction of MPT-dependent apoptosis by Lam D. Our results indicate that functional mitochondria are required for Lam D-induced apoptosis. Inhibition of mitochondrial respiration is responsible for MPT-dependent apoptosis of cancer cells induced by Lam-D.

Lymphangioleiomyomatosis (LAM) is a rare disease, of unknown etiology, affecting women almost exclusively. Microscopically, LAM consists of a diffuse proliferation of smooth muscle cells. LAM can occur without evidence of other disease (sporadic LAM) or in conjunction with tuberous sclerosis complex (TSC). TSC is an autosomal dominant tumor suppressor gene syndrome characterized by seizures, mental retardation, and tumors in the brain, heart, skin, and kidney. LAM commonly presents with progressive breathlessness or with recurrent pneumothorax, chylothorax, or sudden abdominal hemorrhage. Computed tomography (CT) scans show numerous thin-walled cysts throughout the lungs, abdominal angiomyolipomas, and lymphangioleiomyomas. No effective treatment currently exists for this progressive disorder. The prevalence of lymphangioleiomyomatosis is probably underestimated based on its clinical latency and the absence of specific laboratory tests. With the utilization of international LAM data registries the "classical" picture of the disorder appears to be evolving as a larger number of patients are evaluated. An increased awareness of LAM and its common clinical presentation may advance the development of new therapeutic strategies and reduce the number of mistakenly diagnosed patients.

Ethanol extract of four different plants of the Khatra region of the Bankura district of West Bengal, India were evaluated for anti-diarrhoeal activity against different experimental models of diarrhoea in rats. The extracts of Ficus bengalensis Linn. (hanging roots), Eugenia jambolana Lam. (bark), Ficus racemosa Linn. (bark) and Leucas lavandulaefolia Rees (aerial parts) showed significant inhibitory activity against castor oil induced diarrhoea and PGE2 induced enteropooling in rats. These extracts also showed a significant reduction in gastrointestinal motility in charcoal meal tests in rats. The results obtained establish the efficacy of all these plant materials as anti-diarrhoeal agents.

Coronatine is a chlorosis-inducing toxin produced by the plant pathogen Pseudomonas syringae pv atropurpurea. This bacterium is the causal agent of chocolate spot disease, in which brown lesions with chlorotic margins develop on the leaves of Lolium multiflorum Lam. Among the many physiological changes to plants caused by coronatine is the stimulation of ethylene production from bean leaves. The ethyl-substituted side chain of coronatine is an analog of the ethylene precursor, 1-aminocyclopropane-1-carboxylic acid (ACC). We have examined the question of whether part or all of the released ethylene comes from the breakdown of coronatine itself. The rate of ethylene release from leaves of Nicotiana tabacum was proportional to the concentration of coronatine applied to the leaf surface. The lowest effective concentration of coronatine, applied to leaves at 15 pmol cm(-2) of leaf area, resulted in the production of 44 pmol of ethylene cm(-2) over a period of 4 h. The maximum rate of ethylene production occurred 28 to 32 h after application of coronatine. The specific activity of ethylene produced by discs cut from coronatine-treated Nicotiana tabacum leaves floating on a solution containing 10 mm [U-(14)C]methionine was consistent with its exclusive origin from methionine. ACC accumulated in the coronatine-treated tissue. ACC synthase activity increased in Phaseolus aureus hypocotyls during a 6-h treatment with coronatine. Thus, coronatine induces the synthesis of ethylene from methionine.

Combination therapy with adefovir dipivoxil (ADV) and lamivudine (LAM) is recommended for patients infected with LAM-refractory hepatitis B virus (HBV). However, the effects of such therapy on renal function and serum phosphorus levels have not been fully evaluated. Combination therapy with ADV and LAM was given to 37 patients infected with LAM-refractory HBV, including 17 with hepatic cirrhosis. Serum HBV DNA levels decreased to below 2.6 log(10) copies/mL in 23 (62%) of 37 patients at 12 months, 25 (78%) of 32 patients at 24 months, and 16 (84%) of 19 patients at 36 months. Except for one cirrhotic patient, serum alanine aminotransferase levels were below 50 IU/L in all patients during combination therapy. Serum creatinine levels increased in 14 (38%) of 37 patients, and serum phosphate levels decreased to below 2.5 mg/mL in 6 (16%) of 37 patients during combination therapy. Patients who received combination therapy for 36 months or longer had a significantly incidence of elevated serum creatinine levels. Fanconi syndrome occurred in a 57-year-old woman with cirrhosis after ADV was added to LAM. Combination therapy with ADV and LAM can maintain biochemical remission in patients with LAM-refractory HBV. However, the dosing interval of ADV should be adjusted according to renal function and serum phosphate levels in patients receiving long-term treatment.