Trends in perinatal care in developing countries.
Explore the source record for details and available documents.
Developing Countries↗
Biomedical subjects
A Bacci
Publications and source records attributed to A Bacci.
Introducing Evidence-Based Medicine and guidelines for maternal and newborn care in the Republic of Moldova.
Familiarity with Evidence-Based Medicine (EBM) concepts is low amongst key maternal and newborn care clinicians in Moldova. Simple interventions can increase the knowledge of EBM concepts there.
Child Health Services↗
Responsiveness to life-threatening obstetric emergencies in two hospitals in Abidjan, Côte d'Ivoire.
OBJECTIVES: To document the frequency of severe obstetric illness, and the intervals between admission or decision and life-saving surgery and the factors contributing to delays, which were reported during case reviews in two hospitals in Abidjan, Côte d'Ivoire. METHODS: The study was conducted in the teaching hospital in Cocody (CHUC) and the district hospital in Abobo (FSAS) in 2000-01. All severe obstetric cases were inventoried over a period of 1 year, and a subset of cases selected for in-depth review. For the 23 audited cases requiring emergency surgery, the interval between admission/decision and surgery was determined and reasons for the delays examined. FINDINGS: The yearly incidence of severe obstetric morbidity was 224.5 and 11.8 per 1000 live births in the CHUC and FSAS respectively. In CHUC, the decision-to-delivery time was extremely long (median 4.8 h) and this was largely determined by the time needed to obtain a complete surgical kit (median 2.8 h), either because the family had to pay for it in advance or because the kit lacked some essential components, which had to be bought separately. In FSAS, the decision-to-delivery time was much shorter (median 1.0 h). CONCLUSION: The interval between decision and emergency obstetric surgery substantially exceeded the 30 min generally advocated in industrialized countries. The reasons for the long delays were multiple and complex, but the main factors governing them were the huge case load of severe cases and the absence of any clear policy towards ensuring prompt and adequate treatment for life-threatening emergencies. In-depth reviews of cases of severe obstetric morbidity focusing in particular on the timing of emergency treatment could increase the responsiveness of the health system and providers to the needs of women requiring emergency obstetric care.
Cote d'Ivoire↗
Chronic blockade of glutamate receptors enhances presynaptic release and downregulates the interaction between synaptophysin-synaptobrevin-vesicle-associated membrane protein 2.
During development of neuronal circuits, presynaptic and postsynaptic functions are adjusted in concert, to optimize interneuronal signaling. We have investigated whether activation of glutamate receptors affects presynaptic function during synapse formation, when constitutive synaptic vesicle recycling is downregulated. Using primary cultures of hippocampal neurons as a model system, we have found that chronic exposure to both NMDA and non-NMDA glutamate receptor blockers during synaptogenesis produces an increase in miniature EPSC (mEPSC) frequency, with no significant changes in mEPSC amplitude or in the number of synapses. Enhanced synaptic vesicle recycling, selectively in glutamatergic nerve terminals, was confirmed by the increased uptake of antibodies directed against the lumenal domain of synaptotagmin. No increased uptake was detected in neuronal cultures grown in the chronic presence of TTX, speaking against an indirect effect caused by decreased electrical activity. Enhanced mEPSC frequency correlated with a reduction of synaptophysin-synaptobrevin-vesicle-associated membrane protein 2 (VAMP2) complexes detectable by immunoprecipitation. Intracellular perfusion with a peptide that inhibits the binding of synaptophysin to synaptobrevin-VAMP2 induced a remarkable increase of mEPSC frequency in control but not in glutamate receptor blocker-treated neurons. These findings suggest that activation of glutamate receptors plays a role in the downregulation of the basal rate of synaptic vesicle recycling that accompanies synapse formation. They also suggest that one of the mechanisms through which this downregulation is achieved is an increased interaction of synaptophysin with synaptobrevin-VAMP2.
Animals↗
Defective antifungal T-helper 1 (TH1) immunity in a murine model of allogeneic T-cell-depleted bone marrow transplantation and its restoration by treatment with TH2 cytokine antagonists.
Patients undergoing full haplotype-mismatched hematopoietic transplantations may experience severe intractable invasive fungal infections. To verify whether an imbalanced production of T-helper 1 (TH1) and TH2 cytokines may be responsible for susceptibility to fungal infections, C3H/HeJ (H-2(k)) recipient mice were lethally irradiated, received transplantations with T-cell-depleted allogeneic bone marrow (BM) cells from mice of H-2(d) haplotype, and were infected with Candida albicans. At different time-points after transplantation, mice were assessed for pattern of TH cytokine production and susceptibility to infection. The results show that a long-term, donor-type chimerism was achieved as early as 2 weeks after BM transplantation (BMT), at the time when high-level production of TH2 cytokines (interleukin-4 [IL-4] and IL-10) and impaired production of TH1 cytokines (interferon-gamma [IFN-gamma] and IL-12] were observed. At this time, mice were highly susceptible to both disseminated and mucosal infections, as indicated by decreased survival, uncontrolled fungal growth, and failure to develop protective TH1 immunity. However, a predominant production of TH1 cytokines was observed by week 5 after BMT, at the time when mice developed donor-type protective TH1 responses and were resistant to infections. Therapeutic ablation of IL-4 or IL-10 greatly increased resistance to candidiasis. These results indicate that a dysregulated production of TH cytokines occurs in mice undergoing T-cell-depleted allogeneic BMT. The transient predominant production of TH2 cytokines over that of IL-12 impaired the ability of mice to develop antifungal TH1 resistance, an activity that could be efficiently restored upon treatment with TH2 cytokine antagonists.
Animals↗
The plasticity of dendritic cells at the host/fungal interface.
Explore the source record for details and available documents.
Animals↗
Risk factors in Mozambican women with eclampsia: a case-referent study.
In Maputo 133 consecutive eclamptic patients were compared with 393 non-eclamptic referent women. Significant risk factors for eclampsia were age < or = 18 years, household size < or = 3 individuals, unwanted pregnancy, walking to antenatal clinics and, in the thrid trimester, headache, foot oedema, hand or face oedema, epigastric pain, visual disturbance, ear buzzing and dizziness. Significantly more cases than referents reported no blood pressure measurements in antenatal clinics. It is concluded that the quality of antenatal clinics can be improved by enhanced community awareness of danger signs, by early recognition of risk factors and by better management of prodromal symptoms of eclampsia.
Confidence Intervals↗
Different localizations and functions of L-type and N-type calcium channels during development of hippocampal neurons.
Using immunocytochemical assays and patch-clamp and calcium-imaging recordings, we demonstrate that L-type and N-type calcium channels have distinct patterns of expression and distribution and play different functional roles during hippocampal neuron differentiation. L-type channels, which support the depolarization-induced calcium influx in neurons from the very early developmental stages, are functionally restricted to the somatodendritic compartment throughout neuronal development and play a crucial role in supporting neurite outgrowth at early developmental stages. N-type channels, which start contributing at later neuronal differentiation stages (3-4 DIV), are also functionally expressed in the axons of immature neurons. At this developmental stage preceding synaptogenesis, N-type (but not L-type) channels are involved in controlling synaptic vesicle recycling. It is only at later developmental stages (10-12 DIV), when the neurons have established a clear axodendritic polarity and form synaptic contacts, that N-type channels are progressively excluded from the axon. Electrophysiological recordings of single neurons growing in microislands revealed that synaptic maturation coincides with a progressive increase in N-type channels in the somatodendritic region and a progressive decrease in the N-type channels supporting glutamate release from the presynaptic terminal. These results indicate that L-type and N-type calcium channels undergo dynamic, developmentally regulated rearrangements in regional distribution and function and also suggest that different mechanisms may be involved in the sorting and/or stabilization of these two types of channels in different plasma membrane domains during neuronal differentiation.
Animals↗
T cell vaccination in mice with invasive pulmonary aspergillosis.
Aspergillus fumigatus, an opportunistic fungal pathogen, is responsible for multiple airway diseases of an allergic and a nonallergic nature. In a murine model of invasive pulmonary aspergillosis, resistance is associated with a decreased lung inflammatory pathology and the occurrence of an IL-12-dependent Th1-type reactivity that are both impaired by IL-4. In the present study we assess the ability of Aspergillus crude culture filtrate Ags and the recombinant allergen Asp f 2 to induce protective antifungal responses in mice with invasive pulmonary aspergillosis. Similar to what occurred upon nasal exposure to viable A. fumigatus conidia, treatment of immunocompetent mice with Aspergillus crude culture filtrate Ags resulted in the development of local and peripheral protective Th1 memory responses, mediated by Ag-specific CD4+ T cells producing IFN-gamma and IL-2 capable of conferring protection upon adoptive transfer to naive recipients. Protective Th1 responses could not be observed in mice deficient of IFN-gamma or IL-12 and did not occur in response to Asp f 2, which, on the contrary, elicited high level production of inhibitory IL-4. The results show that Ags of Aspergillus exist with the ability to induce both Th1- and Th2-type reactivity during infection, a finding that suggests a possible mechanism through which potentially protective immune responses are inhibited in mice with the infection. However, the occurrence of Th1-mediated resistance upon vaccination with Aspergillus crude culture filtrate Ags, suggests the existence of fungal Ags useful as a candidate vaccine against invasive pulmonary aspergillosis.
Administration, Intranasal↗
Dendritic cells discriminate between yeasts and hyphae of the fungus Candida albicans. Implications for initiation of T helper cell immunity in vitro and in vivo.
The fungus Candida albicans behaves as a commensal as well as a true pathogen of areas highly enriched in dendritic cells, such as skin and mucosal surfaces. The ability of the fungus to reversibly switch between unicellular yeast to filamentous forms is thought to be important for virulence. However, whether it is the yeast or the hyphal form that is responsible for pathogenicity is still a matter of debate. Here we show the interaction, and consequences, of different forms of C. albicans with dendritic cells. Immature myeloid dendritic cells rapidly and efficiently phagocytosed both yeasts and hyphae of the fungus. Phagocytosis occurred through different phagocytic morphologies and receptors, resulting in phagosome formation. However, hyphae escaped the phagosome and were found lying free in the cytoplasm of the cells. In vitro, ingestion of yeasts activated dendritic cells for interleukin (IL)-12 production and priming of T helper type 1 (Th1) cells, whereas ingestion of hyphae inhibited IL-12 and Th1 priming, and induced IL-4 production. In vivo, generation of antifungal protective immunity was induced upon injection of dendritic cells ex vivo pulsed with Candida yeasts but not hyphae. The immunization capacity of yeast-pulsed dendritic cells was lost in the absence of IL-12, whereas that of hypha-pulsed dendritic cells was gained in the absence of IL-4. These results indicate that dendritic cells fulfill the requirement of a cell uniquely capable of sensing the two forms of C. albicans in terms of type of immune responses elicited. By the discriminative production of IL-12 and IL-4 in response to the nonvirulent and virulent forms of the fungus, dendritic cells appear to meet the challenge of Th priming and education in C. albicans saprophytism and infections.
Adoptive Transfer↗
Host immune reactivity determines the efficacy of combination immunotherapy and antifungal chemotherapy in candidiasis.
In immunocompetent mice with candidiasis, successful therapy with amphotericin B and fluconazole relies on the induction of protective, T helper (Th) type 1 responses, an effect potentiated by concomitant interleukin (IL)-4 neutralization. To assess the therapeutic efficacy of combined treatments with antifungals and immunomodulators in conditions of immunosuppression, leukopenic or neutropenic mice with disseminated candidiasis were treated with amphotericin B or fluconazole alone or in combination with soluble IL-4 receptor (sIL-4R) or recombinant (r) IL-12 or IL-10 neutralizing monoclonal antibodies. We found that (1) the synergistic effect of sIL-4R and antifungals is retained in immunocompromised mice; (2) synergism with amphotericin B was superior to that with fluconazole, particularly in leukopenic mice; (3) rIL-12 synergized with fluconazole in neutropenic mice; and (4) IL-10 neutralization was always of limited efficacy. This study indicates that the therapeutic efficacy of antifungals is differentially potentiated by cytokines or cytokine antagonists and is influenced by host immune reactivity.
Amphotericin B↗
Interleukin 18 restores defective Th1 immunity to Candida albicans in caspase 1-deficient mice.
Caspase 1, formerly designated interleukin 1beta (IL-1beta)-converting enzyme, processes pro-IL-1beta and pro-IL-18 to yield active cytokines that play a pivotal role in inflammation and cell activation. We show here the effect of caspase 1 deficiency on the inflammatory and adaptive immune responses to the fungus Candida albicans. Caspase 1 deficiency did not affect susceptibility to primary systemic infection with the fungus, as revealed by survival and fungal growth. However, Th1-mediated resistance to reinfection was greatly impaired in caspase 1-deficient mice, and this correlated with low-level production of IL-12 and gamma interferon. Early in infection, production of these cytokines and that of tumor necrosis factor alpha, IL-6, and, interestingly, IL-1beta occurred normally in caspase 1-deficient mice, while that of IL-18 was severely impaired. Exogenous administration of IL-18, more than IL-12, restored the Th1-mediated resistance to the infection. We conclude that, while caspase 1 is not indispensable for release of mature IL-1beta in candidiasis, the caspase 1-dependent production of IL-18 may represent an important and novel pathway for the expression of sustained Th1 reactivity to the fungus.
Animals↗
Cytokines in candidiasis and aspergillosis.
Both innate and T helper (Th) immunity play a central role in fungal infections. A bi-directional influence exists between the two compartments of the immune system, mainly occurring through cytokine production. On the one hand, protective Th1 or nonprotective Th2 cells mediate resistance or susceptibility to disseminated and localized fungal infections by secreting cytokines with activating or deactivating signals for effector phagocytic cells. On the other hand, cells of the innate immune system regulate the development of antifungal T helper responses by producing directive cytokines, such as interleukin (IL)-12 and IL-10. In experimental models of Candida albicans and Aspergillus fumigatus infections, the administration or neutralization of selective cytokines and the use of cytokine-deficient mice have revealed the existence of a hierarchical pattern of cytokine mediated regulation of antifungal Th cell development and effector function. A finely regulated balance of directive cytokines, rather than the relative absence of opposing cytokines, appears to be required for optimal development and maintenance of protective Th1 reactivity to fungi. Thus, it is conceivable that some cytokines may have beneficial or deleterious effects on infection, depending on the dose and timing of endogenous production or exogenous administration. A better understanding of the different, sometimes unexpected, roles of cytokines is required for their use in prophylaxis and therapy of fungal infections, either alone or in combination with antifungal agents.
Animals↗
In re: Basilar artery migraine and reversible imaging abnormalities.
Explore the source record for details and available documents.
Adolescent↗
Synaptogenesis in hippocampal cultures.
Hippocampal cultures offer unique advantages for the study of neuronal development and synaptogenesis. Studies performed on this model enabled dissection of the temporal sequence of events which lead to the differentiation of pre- and postsynaptic compartments.
Amino Acid Transport System X-AG↗
Tetanus toxin blocks the exocytosis of synaptic vesicles clustered at synapses but not of synaptic vesicles in isolated axons.
Recycling synaptic vesicles are already present in isolated axons of developing neurons (Matteoli et al., Zakharenko et al., 1999). This vesicle recycling is distinct from the vesicular traffic implicated in axon outgrowth. Formation of synaptic contacts coincides with a clustering of synaptic vesicles at the contact site and with a downregulation of their basal rate of exo-endocytosis (Kraszewski et al, 1995; Coco et al., 1998) We report here that tetanus toxin-mediated cleavage of synaptobrevin/vesicle-associated membrane protein (VAMP2), previously shown not to affect axon outgrowth, also does not inhibit synaptic vesicle exocytosis in isolated axons, despite its potent blocking effect on their exocytosis at synapses. This differential effect of tetanus toxin could be seen even on different branches of a same neuron. In contrast, botulinum toxins A and E [which cleave synaptosome-associated protein of 25 kDa. (SNAP-25)] and F (which cleaves synaptobrevin/VAMP1 and 2) blocked synaptic vesicle exocytosis both in isolated axons and at synapses, strongly suggesting that this process is dependent on "classical" synaptic SNAP receptor (SNARE) complexes both before and after synaptogenesis. A tetanus toxin-resistant form of synaptic vesicle recycling, which proceeds in the absence of external stimuli and is sensitive to botulinum toxin F, E, and A, persists at mature synapses. These data suggest the involvement of a tetanus toxin-resistant, but botulinum F-sensitive, isoform of synaptobrevin/VAMP in synaptic vesicle exocytosis before synapse formation and the partial persistence of this form of exocytosis at mature synaptic contacts.
Animals↗
The role of glial cells in synaptic function.
Glial cells represent the most abundant cell population in the central nervous system and for years they have been thought to provide just structural and trophic support to neurons. Recently, several studies were performed, leading to the identification of an active interaction between glia and neurons. This paper focuses on the role played by glial cells at the level of the synapse, reviewing recent data defining how glia is determinant in synaptogenesis, in the modulation of fully working synaptic contacts and in synaptic plasticity.
Animals↗
Antifungal type 1 responses are upregulated in IL-10-deficient mice.
C57BL/6 mice are highly resistant to infections caused by Candida albicans and Aspergillus fumigatus. To elucidate the role of IL-10 produced by C57BL/6 mice during these infections, parameters of infection and immunity to it were evaluated in IL-10-deficient and wild-type mice with disseminated or gastrointestinal candidiasis or invasive pulmonary aspergillosis. Unlike parasitic protozoan infection, C. albicans or A. fumigatus infection did not induce significant acute toxicity in IL-10-deficient mice, who, instead, showed reduced fungal burden and fungal-associated inflammatory responses. The increased resistance to infections as compared to wild-type mice was associated with upregulation of innate and acquired antifungal Th1 responses, such as a dramatically higher production of IL-12, nitric oxide (NO) and TNF-alpha as well as IFN-gamma by CD4+ T cells. Pharmacological inhibition of NO production greatly reduced resistance to gastrointestinal candidiasis, thus pointing to the importance of IL-10-dependent NO regulation at mucosal sites in fungal infections. These results are reminiscent of those obtained in genetically susceptible mice, in which IL-10 administration increased, and IL-10 neutralization decreased, susceptibility to C. albicans and A. fumigatus infections. Collectively, these observations indicate that the absence of IL-10 augments innate and acquired antifungal immunity by upregulating type 1 cytokine responses. The resulting protective Th1 responses lead to a prompt reduction of fungal growth, thus preventing tissue destruction and lethal levels of proinflammatory cytokines.
Animals↗