Building back better: resilient environmental and occupational health systems for the next global crisis

@#Even after two years, the COVID-19 pandemic still disrupts public activities and services as it exposes vulnerabilities among the population and negatively impacts environmental conditions. The crisis also impeded global progress toward achieving Sustainable Development Goals (SDG). The Fourth Environmental and Occupational Health (EOH) Forum held virtually on November 25 to 26, 2021 provided a venue for learning about local and international COVID-19 responses to help prepare for the next global crisis. Through the systems thinking approach, the discussions prioritized analyses of leadership and governance, financing, human resource, technologies, information management, and service delivery. These analyses focused on community and/or workplace programs and services linked to air quality, waste management, psychosocial wellness, and COVID-19 vaccination. The forum amplified calls for climate actions and public health improvement and emphasized the significance of a collaborative, evidence-based, integrated public health response to a crisis underscoring the apparent interdependence of the SDGs.

Characteristics of COVID-19 positive pregnant patients admitted in a private tertiary hospital and their maternal and neonatal outcomes / Philippine Journal of Obstetrics and Gynecology

Introduction@#The severe acute respiratory syndrome coronavirus 2 pandemic has had profound effects globally. Historical experience with previous Coronaviruses has shown increased maternal and perinatal morbidity and mortality, theoretically secondary to the physiologic changes of pregnancy. As of August 2021, the Philippines is the 23rd top country worldwide in terms of total number of cases, yet there remains to be a sparse pool of information both internationally and locally@*Objectives@#This study aims to present the prevalence, clinical characteristics, as well as the neonatal, obstetric, and maternal outcomes of all pregnant women admitted in the institution who had active or previous COVID‑19 infection@*Methodology@#Retrospective review of data using the hospital’s health information system was utilized. Within the study period, all admitted obstetric patients who had at least one positive result in a RT‑PCR naso‑oropharyngeal swab for SARS‑CoV‑2 were included in this study and categorized into: (1) symptomatic, (2) recovered, and (3) asymptomatic@*Results@#A total of 48 patients were included in the study, where prevalence of COVID‑19 in pregnancy was 3.65%. Results showed that most patients were in the third trimester, and contrary to the non‑pregnant population, majority (60.41%) did not have comorbidities. Most remained asymptomatic (33.33%) or had mild symptoms (18.75%), and underwent abdominal delivery (50%) for obstetric indications. COVID‑19 status was not associated with adverse obstetric outcomes in this study population, but had significant association with preterm birth (p=0.019) and NICU admission (P=<0.001@*Conclusion@#Overall, most cases were asymptomatic and had good prognosis even with the adaptations a pregnant woman undergoes. In addition, neonatal outcomes were generally good regardless of the association with preterm birth and NICU admission. Lastly, there was no appreciated evidence for vertical transmission

The Bloch point 3D topological charge induced by the magnetostatic interaction.

A hedgehog or Bloch point is a point-like 3D magnetization configuration in a ferromagnet. Regardless of widely spread treatment of a Bloch point as a topological defect, its 3D topological charge has never been calculated. Here, applying the concepts of the emergent magnetic field and Dirac string, we calculate the 3D topological charge (Hopf index) of a Bloch point and show that due to the magnetostatic energy contribution it has a finite, non-integer value. Thus, Bloch points form a new class of hopfions-3D topological magnetization configurations. The calculated Bloch point non-zero gyrovector leads to important dynamical consequences such as the appearance of topological Hall effect.

Inactivation of SARS Coronavirus 2 and COVID-19 patient samples for contemporary immunology and metabolomics studies

In late 2019, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged from Wuhan, China spurring the Coronavirus Disease-19 (COVID-19) pandemic that has resulted in over 219 million confirmed cases and nearly 4.6 million deaths worldwide. Intensive research efforts ensued to constrain SARS-CoV-2 and reduce COVID-19 disease burden. Due to the severity of this disease, the US Centers for Disease Control and Prevention (CDC) and World Health Organization (WHO) recommend that manipulation of active viral cultures of SARS-CoV-2 and respiratory secretions from COVID-19 patients be performed in biosafety level 3 (BSL3) containment laboratories. Therefore, it is imperative to develop viral inactivation procedures that permit samples to be transferred and manipulated at lower containment levels (i.e., BSL2), and maintain the fidelity of downstream assays to expedite the development of medical countermeasures (MCMs). We demonstrate optimal conditions for complete viral inactivation following fixation of infected cells with paraformaldehyde solution or other commonly-used branded reagents for flow cytometry, UVC inactivation in sera and respiratory secretions for protein and antibody detection assays, heat inactivation following cDNA amplification of single-cell emulsions for droplet-based single-cell mRNA sequencing applications, and extraction with an organic solvent for metabolomic studies. Thus, we provide a suite of protocols for viral inactivation of SARS-CoV-2 and COVID-19 patient samples for downstream contemporary immunology assays that facilitate sample transfer to BSL2, providing a conceptual framework for rapid initiation of high-fidelity research as the COVID-19 pandemic continues.

Pathogenic neutrophilia drives acute respiratory distress syndrome in severe COVID-19 patients

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the ensuing COVID-19 pandemic have caused [~]40 million cases and over 648,000 deaths in the United States alone. Troubling disparities in COVID-19-associated mortality emerged early, with nearly 70% of deaths confined to Black/African-American (AA) patients in some areas, yet targeted studies within this demographic are scant. Multi-omics single-cell analyses of immune profiles from airways and matching blood samples of Black/AA patients revealed low viral load, yet pronounced and persistent pulmonary neutrophilia with advanced features of cytokine release syndrome and acute respiratory distress syndrome (ARDS), including exacerbated production of IL-8, IL-1{beta}, IL-6, and CCL3/4 along with elevated levels of neutrophil elastase and myeloperoxidase. Circulating S100A12+/IFITM2+ mature neutrophils are recruited via the IL-8/CXCR2 axis, which emerges as a potential therapeutic target to reduce pathogenic neutrophilia and constrain ARDS in severe COVID-19. Graphical AbstractThe lung pathology due to severe COVID-19 is marked by a perpetual pathogenic neutrophilia, leading to acute respiratory distress syndrome (ARDS) even in the absence of viral burden. Circulating mature neutrophils are recruited to the airways via IL-8 (CXCL8)/CXCR2 chemotaxis. Recently migrated neutrophils further differentiate into a transcriptionally active and hyperinflammatory state, with an exacerbated expression of IL-8 (CXCL8), IL-1{beta} (IL1B), CCL3, CCL4, neutrophil elastase (NE), and myeloperoxidase (MPO) activity. Airway neutrophils and recruited inflammatory monocytes further increase their production of IL-8 (CXCL8), perpetuating lung neutrophilia in a feedforward loop. MdCs and T cells produce IL-1{beta} and TNF, driving neutrophils reprogramming and survival. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=142 SRC="FIGDIR/small/446468v2_ufig1.gif" ALT="Figure 1"> View larger version (43K): org.highwire.dtl.DTLVardef@81fd3aorg.highwire.dtl.DTLVardef@181e63org.highwire.dtl.DTLVardef@172fedcorg.highwire.dtl.DTLVardef@ba55a7_HPS_FORMAT_FIGEXP M_FIG C_FIG

ACE2 expression in rat brain: implications for COVID-19 associated neurological manifestations

We examined cell type-specific expression and distribution of rat brain angiotensin converting enzyme 2 (ACE2), the receptor for SARS-CoV-2, in rodent brain. ACE2 is ubiquitously present in brain vasculature, with the highest density of ACE2 expressing capillaries found in the olfactory bulb, the hypothalamic paraventricular, supraoptic and mammillary nuclei, the midbrain substantia nigra and ventral tegmental area, and the hindbrain pontine nucleus, pre-Botzinger complex, and nucleus of tractus solitarius. ACE2 was expressed in astrocytes and astrocytic foot processes, pericytes and endothelial cells, key components of the blood-brain-barrier. We found discrete neuronal groups immunopositive for ACE2 in brainstem respiratory rhythm generating centers including the pontine nucleus, the parafascicular/retrotrapezoid nucleus, the parabrachial nucleus, the Botzinger and pre-Botzinger complex and the nucleus of tractus solitarius; in arousal-related pontine reticular nucleus and in gigantocellular reticular nuclei; in brainstem aminergic nuclei, including substantia nigra, ventral tegmental area, dorsal raphe, and locus coeruleus; in the epithalamic habenula, hypothalamic paraventricular and suprammamillary nuclei; and in the hippocampus. Identification of ACE2-expressing neurons in rat brain within well-established functional circuits facilitates prediction of possible neurological manifestations of brain ACE2 dysregulation during and after COVID-19 infection. HighlightsO_LIACE2 is present in astrocytes, pericytes, and endothelia of the blood brain barrier. C_LIO_LINeuronal ACE2 expression is shown in discrete nuclei through the brain. C_LIO_LIBrainstem breathing, arousal-related, hypothalamic and limbic nuclei express ACE2. C_LIO_LIACE2 is expressed in circuits potentially involved in COVID-19 pathophysiology. C_LI

Revealing Polymorphic Phase Transformations in Polymer-Based Hot Melt Extrusion Processes.

The inadvertent occurrence of polymorphic phase transformations in active pharmaceutical ingredients (APIs) during hot melt extrusion (HME) processes has been claimed to limit the application of this technique. Hence, the control of polymorphism would need to be addressed if there is any prospect of HME to be successfully implemented as an alternative solid dosage formulation strategy in integrated, continuous end-to-end pharmaceutical manufacturing settings. This work demonstrates that flufenamic acid (FFA), one of the most polymorphic APIs known, thus far, can be processed using temperature-simulated HME with polyethylene glycol (PEG) as polymeric carrier. At temperatures above the transition point of FFA forms III and I (42 °C), the induction time of the polymorphic phase transformation is longer than the average reported residence time in conventional HME processes (5 min). Moreover, it was demonstrated that thorough understanding of the thermodynamic and kinetic design space for the PEG-FFA system leads to polymorphic control in the produced crystalline solid dispersions. Ultimately, this investigation helps to gain fundamental understanding of the processing needs of crystalline solid dispersions, which will lead to the broader application of HME as a continuous manufacturing strategy for drug products containing APIs prone to polymorphism, representing about 80% of all APIs.

Analysis of gaps among stakeholders of occupational health and safety in the Philippines

@#<p style="text-align: justify;"><strong>OBJECTIVE:</strong> Increase of occupational injuries, accidents or diseases, has become a global trend. Implementation of programs on Occupational Health and Safety (OHS) programs are weak, however. Strengthening the OHS, stakeholders and their constituents must take the driver's seat for policy formulation program development and services. This study determined the gaps of the OHS stakeholders in the Philippines.</p><p style="text-align: justify;"><strong>METHODS:</strong> Data were gathered through review of relevant documents, series of key informant interviews and a workshop.</p><p style="text-align: justify;"><strong>RESULTS AND CONCLUSIONS:</strong> The investigators were able to identify 27 stakeholders. Results showed gaps that focused mainly on governance. These include: (1) lack of a dedicated national agency that will oversee all OHS initiatives across industries and sectors; (2) inadequate awareness on OHS mandate of some agencies; (3) unclear delineation of roles and responsibilities among stakeholders; (4) poor coordination among government agencies; and (5) poor enforcement of OHS legislations. These gaps should be addressed to ensure effective and efficient implementation of the policies.</p>

Occupational noise exposure of traffic enforcers in selected streets in the City of Manila

@#<p style="text-align: justify;"><strong>OBJECTIVE:</strong> The study aimed to evaluate the sound pressure levels of selected traffic enforcer sites in the City of Manila.</p><p style="text-align: justify;"><strong>METHODOLOGY:</strong> A Brüel & Kjær Integrating Sound Level Meter type 2225 was used to measure sound pressure levels in dB(A) to estimate personal noise exposure of traffic enforcers designated at Quezon Boulevard near Quiapo Church and Recto - Rizal Avenue on a weekday and a weekend. Graphs were generated while appropriate measures were calculated for the noise exposure levels. The mean exposure levels were compared with the Philippine Occupational Safety and Health standards by computing the corresponding permissible exposure limit for each work shift using the Equal Energy Principle.17</p><p style="text-align: justify;"><strong>RESULTS:</strong> Noise exposure levels at Quezon Boulevard ranged from 75.0 dB(A) to 91.5 dB(A) with mean noise exposure level of 84.3 ± 3.7 dB(A) and 82.5 ± 2.6 dB(A) for the weekday AM and PM shift, respectively. The mean noise exposure level at Quezon Boulevard for the weekend AM shift was 82.4 ± 2.6, whereas 80.4 ± 2.8 for the PM shift. The noise exposure levels at Recto - Rizal Avenue ranged from 81.5 dB(A) to 99.3 dB(A) with mean noise exposure level of 86.7 ± 2.6 dB(A) and 86.0 ± 2.1 dB(A) for the weekday AM and PM shift, respectively. The mean noise exposure level at Recto - Rizal Avenue for the weekend AM shift was 86.7 ± 2.3, whereas 89.0 ± 4.0 for the PM shift.</p><p style="text-align: justify;"><strong>CONCLUSION:</strong> The study showed that traffic enforcers designated at Quezon Boulevard and Recto - Rizal Avenue are exposed to noise levels that do not exceed the Philippine Occupational Safety and Health standards.</p>

Lead, cadmium and zinc in hair samples: relationship with dietary habits and urban environment.

This study was performed in order to analyze the relationships between hair zinc, lead, and cadmium with the kind of diet consumed (by recall of the diet consumed the previous 14 days), living area (urban or rural), tobacco smoking, and body mass index (BMI) among 419 individuals of the Canary Archipelago. Median values and interquartile range were 43 µg/g (18.50-132.50) for zinc, 4.09 µg/g (2.19-8.38) for lead, and 0.128 µg/g (0.05-0.30) for cadmium. We observed that hair zinc was markedly elevated among those consuming fish more frequently and, to a lesser amount, among those who consumed meat frequently, among those living in urban areas, and among those with BMI over 25 kg/m(2), keeping a significant relationship with BMI. Hair lead was also higher among fish consumers, showed a trend to higher values among inhabitants of urban areas, and was lower among obese individuals. Hair cadmium was higher among those who consumed less vegetables and fruits. By multivariate analysis, introducing the variables meat, fish, and vegetable consumption, urban/rural; sex; age; and BMI values, we observed that fish consumption (beta = 0.15) was the only variable independently associated to higher zinc levels; fish consumption (beta = 0.15) and meat consumption (beta = 0.17) were related to high cadmium levels, whereas meat consumption was significantly associated to higher hair lead levels (beta = 0.15). Therefore, we conclude that hair zinc, cadmium, and lead seem to depend more heavily on dietary habits than on tobacco consumption or living in rural or urban areas.

The exopolysaccharide of Xylella fastidiosa is essential for biofilm formation, plant virulence, and vector transmission.

Exopolysaccharides (EPS) synthesized by plant-pathogenic bacteria are generally essential for virulence. The role of EPS produced by the vector-transmitted bacterium Xylella fastidiosa was investigated by knocking out two genes implicated in the EPS biosynthesis, gumD and gumH. Mutant strains were affected in growth characteristics in vitro, including adhesion to surfaces and biofilm formation. In addition, different assays were used to demonstrate that the mutant strains produced significantly less EPS compared with the wild type. Furthermore, gas chromatography-mass spectrometry showed that both mutant strains did not produce oligosaccharides. Biologically, the mutants were deficient in movement within plants, resulting in an avirulent phenotype. Additionally, mutant strains were affected in transmission by insects: they were very poorly transmitted by and retained within vectors. The gene expression profile indicated upregulation of genes implicated in cell-to-cell signaling and adhesins while downregulation in genes was required for within-plant movement in EPS-deficient strains. These results suggest an essential role for EPS in X. fastidiosa interactions with both plants and insects.

Differences in virulence and immune response induced in a murine model by isolates of Mycobacterium ulcerans from different geographic areas.

Buruli ulcer (BU) is the third most common mycobacterial disease in immunocompetent hosts. BU is caused by Mycobacterium ulcerans, which produces skin ulcers and necrosis at the site of infection. The principal virulence factor of M. ulcerans is a polyketide-derived macrolide named mycolactone, which has cytotoxic and immunosuppressive activities. We determined the severity of inflammation, histopathology and bacillary loads in the subcutaneous footpad tissue of BALB/c mice infected with 11 different M. ulcerans isolates from diverse geographical areas. Strains from Africa (Benin, Ghana, Ivory Coast) induced the highest inflammation, necrosis and bacillary loads, whereas the strains collected from Australia, Asia (Japan, Malaysia, New Guinea), Europe (France) and America (Mexico) induced mild inflammation. Subsequently, animals were infected with the strain that exhibited the highest (Benin) or lowest (Mexico) level of virulence in order to analyse the local immune response generated. The Mexican strain, which does not produce mycolactone, induced a predominantly T helper type 1 (Th1) cytokine profile with constant high expression of the anti-microbial peptides beta defensins 3 and 4, in co-existence with low expression of the anti-inflammatory cytokines interleukin (IL)-10, IL-4 and transforming growth factor (TGF)-beta. The highly virulent strain from Benin which produces mycolactone A/B induced the opposite pattern. Thus, different local immune responses were found depending on the infecting M. ulcerans strain.

[Circulating anticoagulant and focal liver lesions associated to rich clinical expression in the secondary syphilis]. / Anticoagulante circulante y lesiones focales hepáticas asociados a marcada semiología sistémica en la lúes secundaria.

A 37-year-old male was admitted at our hospital for evaluation of clinical presentation of 8 weeks evolution of malaise, fever, sore throat and nose, arthralgias, holocraneal headache, photophobia and nausea. With the shower he noticed spots in palms of hands and plants of feet. A year before had noticed painless erosions in foreskin. He had risk factors for sexual transmission diseases. The analytical showed criteria of dissociated colestasis, nephrotic syndrome, presence of circulating anticoagulant, and positivity for the reaginic and specific serological syphilis. In an abdominal ultrasonic multiple, focal and small liver lesions were watched. With two weeks of treatment with penicillin the clinical manifestations reverted, and the analytical and of image was watched bettering, which dissapeared at the three months of treatment. We comment the rich clinical expression and the peculiarities of presenting focal liver lesions and circulating anticoagulant, in a case of secondary syphilis.

Vacunas y timerosal:: ¿riesgo de autismo y desórdenes neurológicos? / Thimerosal and vaccines: ¿austims and neurological disorders?

Con el avance de la ciencias médicas numerosas enfermedades han podido ser prevenidas antes de que se produzcan gracias a las vacunas. De este modo se han evitado millones de muertes reduciéndose la mortalidad y morbildad por dichas enfermedades inmunoprevenibles, en aquellas poblaciones en donde las campañas de vacunación se realizan. Sin embargo las vacunas pueden presentar efectos o eventos no deseados relacionados con la aplicación de la mismas, los cuales aunque infrecuentes en su mayoría han sido muchas veces magnificados. Últimamente se ha venido tratando de implicar a un preservante de las vacunas el timerosal como el posible causante de autismo, atrubuyéndosele un efecto neurotóxico. Debido a que los grados de evidencia con las que se trata de sustentar dichas aseveraciones no son los adecuados, y que a la luz del conocimiento actual, los estudios no demuestran una asociación entre vacunas que contienen timerosal y desórdenes del espectro autístico; se concluye que las evidencias actuales señalan que no existe una relación causal entre un tipo de vacunas (SRP) o si éstas contienen timerosal y el desarrollo de autismo o un desorden del espectro autístico.

It has been possible to prevent many diseases thanks to the advance of the medical sciences and the development of effective vaccines. Millions of deaths have been avoided, and the mortality and morbidity of vaccine-preventable diseases have been drastically reduced, in the populations where vaccine campaigns are carried out. Vaccines, nevertheless, can present undesirable effects or events related to their application, which despite their rarity have been grossly exaggerated. Lately there are attempts to imply thimerosal, a vaccine preservant, as the possible cause of autism, attributing to it a neurotoxic effect. The present evidences of many different kinds do not support a neurotoxic role for thimerosal. The statements on thimerosal neurotoxicity are not supported by evidence; the studies show no association between vaccines containing thimerosal and disorders of the autistic spectrum. The conclusion is that there is no causal effect between a type of vaccines or whether they contain thimerosal and the development of a neurological disorder of the autistic spectrum.

Immunogenicity and protection induced by Mycobacterium tuberculosis mce-2 and mce-3 mutants in a Balb/c mouse model of progressive pulmonary tuberculosis.

Mycobacterial proteins coded by the mammalian cell entry (mce) genes allow for cell invasion into the host. The Mycobacterium tuberculosismce-2 and mce-3 mutants have impaired synthesis of mce proteins and are attenuated in BALB/c mice. Intra-tracheal infection of Balb/c mice with either mce mutant induced lower but progressive production of IFN-gamma and TNF-alpha, as well as larger delayed type hypersensitivity (DTH) reactions, than their parental H37Rv strain. When used as a subcutaneous vaccine and, before challenge, both mutants were more attenuated than BCG in Balb/c and immunodeficient nude mice. Cell suspensions from lymph nodes and spleen from mce mutant vaccinated mice stimulated with mycobacterial culture filtrate antigens (CFA) or immunodominant antigens (ESAT-6, Ag85) produced more INF-gamma than BCG-vaccinated animals. Used as subcutaneous vaccines, 60 days before intra-tracheal challenge with the hypervirulent strain of M. tuberculosis (Beijing code 9501000), both mutants induced a higher level of protection than BCG; 72% and 63% of the mice vaccinated with the mce-2 and mce-3 mutants, respectively, survived for 16 weeks after the challenge as compared to 30% of those vaccinated with BCG. Likewise, there was less tissue damage (pneumonia) and lower colony forming units (CFU) in the mice vaccinated with either of the two mutants as compared to the findings in mice vaccinated with BCG. These data suggest that lack of mce-2 and -3 gene expression decreases virulence and increases immunogenicity of live vaccines, favouring their ability to protect against tuberculosis, which was better than the protection conferred by BCG.

Production, partial characterization and mass spectrometric studies of the extracellular laccase activity from Fusarium proliferatum.

Benzyl alcohol and starch-free commercial wheat bran were effective inducers of the laccase activity in cultures of Fusarium proliferatum (MUCL 31970). Initial pH value in the cultures was also an overriding factor for increasing its production. By gel permeation high-performance liquid chromatography, the enzyme eluted as an apparently homogeneous peak with a molecular mass of 54 kDa, but by isoelectrofocusing, two proteins with pI values of 5.17 and 5.07 were revealed. Two different phenoloxidase activities were also detected after nondenaturing polyacrylamide gel electrophoresis. By matrix-assisted laser desorption/ionization-time of flight-mass spectrometry (MALDI-TOF-MS), both proteins showed unique fingerprints, so they were classifiable as isozymes, and were named laccase 1 (Lac1, pI 5.17) and laccase 2 (Lac2, pI 5.07). No clear matches were found when compared with other proteins. The tandem mass spectrometry of some peptides from both isozymes reanalyzed by nanoelectron ionization-ion trap-mass spectrometry (nESI-IT-MS) confirmed their unique character. The following interesting properties, particularly its stability at alkaline pH, make this laccase a promising industrial enzyme for biotechnological applications: maximum activity at 60 degrees C, thermal stability for 2 h at 40 degrees C, optimum pH 3.5 (km=62 microM) measured on 2,2'-azino-bis(3-ethylbenz-thiazoline-6-sulfonate), and pH stability 4-8 (75% stability at pH levels 2.2 and 9) for 2 h at 25 degrees C.

Immunogenicity and protective efficacy of the Mycobacterium tuberculosis fadD26 mutant.

The Mycobacterium tuberculosis fadD26 mutant has impaired synthesis of phthiocerol dimycocerosates (DIM) and is attenuated in BALB/c mice. Survival analysis following direct intratracheal infection confirmed the attenuation: 60% survival at 4 months post-infection versus 100% mortality at 9 weeks post-infection with the wild-type strain. The fadD26 mutant induced less pneumonia and larger DTH reactions. It induced lower but progressive production of interferon (IFN)-gamma, interleukin (IL)-4 and tumour necrosis factor (TNF)-alpha. Used as a subcutaneous vaccine 60 days before intratracheal challenge with a hypervirulent strain of M. tuberculosis (Beijing code 9501000), the mutant induced a higher level of protection than did Bacille Calmette-Guérin (BCG). Seventy per cent of the mice vaccinated with the fadD26 mutant survived at 16 weeks after challenge compared to 30% of those vaccinated with BCG. Similarly, there was less tissue damage (pneumonia) and lower colony-forming units (CFU) in the mice vaccinated with the fadD26 mutant compared to the findings in mice vaccinated with BCG. These data suggest that DIM synthesis is important for the pathogenicity of M. tuberculosis, and that inactivation of DIM synthesis can increase the immunogenicity of live vaccines, and increase their ability to protect against tuberculosis.

Local production of nitric oxide in patients with tuberculosis.

Nitric oxide (NO), produced by the inducible nitric oxide synthase (iNOS), is important in host defence against Mycobacterium tuberculosis in rodents, but the presence of high-output NO production in human tuberculosis has been controversial. We investigated iNOS and nitrotyrosine (Ntyr) expression in pleural (n = 7), pulmonary (n = 5) and lymph node biopsies (n = 5) from untreated, newly diagnosed tuberculosis patients. Many iNOS and Ntyr reactive macrophages were observed in granulomas, including Langhans giant cells, indicating high-output NO production at the primary site of disease in tuberculosis.

Ajoene and 5-fluorouracil in the topical treatment of Cladophialophora carrionii chromoblastomycosis in humans: a comparative open study.

Ajoene and 5-fluorouracil (5-FU) are compounds that have shown in-vitro activity against Cladophialophora carrionii, an important etiologic agent of chromoblastomycosis. An open comparative trial was conducted to assess safety and effectiveness of topical ajoene and 5-FU in the treatment of localized chromoblastomycosis. Thirty-seven patients with a clinically and mycologically confirmed diagnosis were randomly distributed into two groups allocated to ajoene (0.5% gel; n = 19) or 5-FU (1% cream; n = 18). Topical treatment was applied to localized lesions (< or = 2.5-cm diameter) once a day, with occlusion, for 12-16 weeks. Complete clinical and mycological remission was achieved in 14/19 patients (74%) treated with ajoene and 14/18 patients (78%) treated with 5-FU. All 5-FU-treated patients developed a post-treatment scar at the site of the lesion, while ajoene-treated patients showed only a slight depigmentation of the skin. The differences observed in cure rate between ajoene and 5-FU are not statistically significant. Follow-up of all patients for 4 years revealed no relapses in the ajoene-treated group, while one patient in the 5-FU-treated group had a relapse 6 months after the end of therapy. This trial represents the first clinical use of ajoene in the control of a deep mycosis.