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SETTING: TB infection (TBI) is diagnosed using the technique-dependent tuberculin skin test (TST) or costly, more accurate interferon-gamma release assays. The TST (⩾10 mm) threshold was indicated by previous research among household contacts in Vietnam, but routine implementation with a different tuberculin reagent showed unexpectedly low TST positivity. OBJECTIVE: TST (⩾5 mm and ⩾10 mm) results were compared to QuantiFERON™-TB Gold Plus (QFT) results in household contacts during community campaigns in 2020 and 2021. DESIGN: This was a cross-sectional multi-center implementation study. RESULTS: Among 1,330 household contacts in 2020, we found a TBI prevalence of 38.6% (QFT), similar to TST ⩾5 mm (37.4%) and higher than TST ⩾10 mm (13.1%). QFT+/TST+ was higher for TST ⩾5 mm (20.7%) than TST ⩾10 mm (9.4%). QFT was not discordant with TST ⩾5 mm (McNemar's test = 0.6, P = 0.5) but was discordant with TST ⩾10 mm (McNemar's test = 263.9, P < 0.01). Older age and Southern region increased odds for positive TST ⩾5 mm and QFT with weaker associations for TST ⩾10 mm. Agreement and discordance were similar in 2021 for 1,158 household contacts. CONCLUSION: Tuberculin reagents affect TST positivity rates. High TB burden countries should monitor reliability of TBI diagnosis, including tuberculin potency, cold chain, and TST technique to optimize eligibility for TB preventive treatment.
CONTEXTE: L'infection tuberculeuse (TBI) est diagnostiquée à l'aide du test cutané à la tuberculine (TST), qui dépend de la technique, ou de tests de libération de l'interféron-gamma, coûteux et plus précis. Des recherches antérieures ont indiqué que le TST (⩾10 mm) est généralement utilisé pour diagnostiquer la TB parmi les contacts familiaux au Vietnam ; la mise en Åuvre de routine avec un réactif de tuberculine différent a montré une faible positivité inattendue du TST. OBJECTIF: Les résultats du TST (⩾5 mm et ⩾10 mm) ont été comparés aux résultats de QuantiFERON™-TB Gold Plus (QFT) chez les contacts familiaux au cours des campagnes communautaires de 2020 et 2021. MÉTHODE: Il s'agissait d'une étude transversale multicentrique de mise en Åuvre. RÉSULTATS: Parmi 1 330 contacts familiaux en 2020, nous avons trouvé une prévalence de TBI de 38,6% (QFT), similaire au TST ⩾5 mm (37,4%) et plus élevée que le TST ⩾10 mm (13,1%). Le QFT+/TST+ était plus élevé pour le TST ⩾5 mm (20,7%) que pour le TST ⩾10 mm (9,4%). Le QFT n'était pas discordant avec le TST ≥5 mm (test de McNemar = 0,6 ; P = 0,5) mais était discordant avec le TST ⩾10 mm (test de McNemar = 263,9 ; P < 0,01). L'âge avancé et la région méridionale augmentaient les probabilités d'un TST positif ⩾5 mm et d'un QFT, avec des associations plus faibles pour un TST ⩾10 mm. La concordance et la discordance étaient similaires en 2021 pour 1 158 contacts familiaux. CONCLUSION: Les réactifs de tuberculine affectent les taux de positivité des TST. Les pays à forte charge de TB doivent surveiller la fiabilité du diagnostic de TBI, y compris la puissance de la tuberculine, la chaîne du froid et la technique du TST afin d'optimiser l'éligibilité au traitement préventif de la TB.
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BACKGROUND: Drug resistance poses a major barrier to global control of TB - a leading infectious cause of death. Depression and stigma occur commonly among people with TB. However, the relationship between drug-resistant forms of TB, depression and stigma are not well understood.OBJECTIVE: To compare depression, stigma and health-related quality of life (HRQoL), among people with drug-susceptible TB (DS-TB) and multidrug-resistant TB (MDR-TB).METHODS: A cross-sectional study of people treated for DS-TB and MDR-TB in four provinces of Vietnam. The survey included a stigma scale (Vietnamese Tuberculosis Stigma Scale), depression scale (9-item Patient Health Questionnaire) and HRQoL scale (Functional Assessment of Chronic Illness Therapy - Tuberculosis). Differences between the two populations were compared using linear regression.RESULTS: Eighty-one people with DS-TB and 315 people with MDR-TB participated in the study. People with MDR-TB had a higher prevalence of depression than those with DS-TB (difference 17.8%, χ² 8.64). The mean depression and stigma scores were higher for people with MDR-TB than those with DS-TB (adjusted difference [AD] 8.6 and 7.6 respectively). People with MDR-TB reported lower HRQoL than those with DS-TB (AD -23.8).CONCLUSION: Depression and stigma are common among people with TB in Vietnam. Strategies to prevent and treat depressive symptoms and stigma in people with TB are critical to a holistic, patient-centred approach to care.
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Preparaciones Farmacéuticas , Tuberculosis Resistente a Múltiples Medicamentos , Antituberculosos/uso terapéutico , Estudios Transversales , Depresión/epidemiología , Humanos , Calidad de Vida , Tuberculosis Resistente a Múltiples Medicamentos/tratamiento farmacológico , Tuberculosis Resistente a Múltiples Medicamentos/epidemiología , Vietnam/epidemiologíaRESUMEN
OBJECTIVES: It has been reported that green tea exerts antibacterial, anti-inflammatory, and antioxidant effects. The purpose of the present study was to evaluate the effects of drinking green tea on bone resorption in ligature-induced periodontitis in mice. METHODS: Sixty C57BL/6 eight-week-old male mice were used. To induce periodontitis, a ligature was placed for 7 days around the upper left second maxillary molar. After ligature removal, the animals were administered different concentrations of green tea (1.5 g/60 mL, 3 g/60 mL, or 6 g/60 mL) or distilled water. At 1 and 2 weeks of administration, the animals were sacrificed and micro-CT images of the maxillae were taken. Next, the depth and area of alveolar bone loss in the buccal and palatal sides were measured. The number of inflammatory cells and osteoclasts in histological sections were counted. RESULTS: The result showed ligature-induced alveolar bone loss. Green tea inhibited ligature-induced bone loss in the buccal side in a dose-dependent manner. Histologically, ligature increased the number of inflammatory cells and osteoclasts, but this effect was alleviated by green tea. CONCLUSIONS: Evidence from this animal experiment suggested that drinking green tea would be potentially beneficial to reduce alveolar bone loss in ligature-induced periodontitis.
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Pérdida de Hueso Alveolar , Periodontitis , Animales , Masculino , Ratones , Ratones Endogámicos C57BL , Osteoclastos , TéRESUMEN
BACKGROUND: Tuberculosis is the leading infectious cause of death. Steep reductions in tuberculosis-related mortality are required to realize the World Health Organization's "End Tuberculosis Strategy." However, accurate mortality estimates are lacking in many countries, particularly following discharge from care. This study aimed to establish the mortality rate among patients with pulmonary tuberculosis in Vietnam and to quantify the excess mortality in this population. METHODS: We conducted a prospective cohort study among adult patients treated for smear-positive pulmonary tuberculosis in 70 clinics across Vietnam. People living in the same households were recruited as controls. Participants were re-interviewed and their survival was established at least 2 years after their treatment with an 8-month standardized regimen. The presence of relapse was established by linking identifying data on patients and controls to clinic registries. Verbal autopsies were performed. The cumulative mortality among patients was compared to that among a control population, adjusting for age and gender. RESULTS: We enrolled 10964 patients and 25707 household controls. Among enrolled tuberculosis patients, 9% of patients died within a median follow-up period of 2.9 years: 342 (3.1%) during treatment and 637 (5.8%) after discharge. The standardized mortality ratio was 4.0 (95% confidence interval 3.7-4.2) among patients with tuberculosis, compared to the control population. Tuberculosis was the likely cause of death for 44.7% of these deceased patients. CONCLUSIONS: Patients treated for tuberculosis had a markedly elevated risk of death, particularly in the post-treatment period. Interventions to reduce tuberculosis mortality must enhance the early detection of drug-resistance, improve treatment effectiveness, and address non-communicable diseases.
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Tuberculosis Pulmonar/epidemiología , Tuberculosis Pulmonar/mortalidad , Adulto , Antituberculosos/uso terapéutico , Autopsia , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Recurrencia , Tuberculosis Pulmonar/tratamiento farmacológico , Vietnam/epidemiología , Adulto JovenRESUMEN
UNLABELLED: Tuberculosis (TB) and human immunodeficiency virus (HIV) infection are leading causes of disease and death in Vietnam, but TB/HIV disease trends and the profile of co-infected patients are poorly described. METHODS: We examined national TB and HIV notification data to provide a geographic overview and describe relevant disease trends within Vietnam. We also compared the demographic and clinical profiles of TB patients with and without HIV infection. RESULTS: During the past 10 years (2005-2014) cumulative HIV case numbers and deaths increased to 298,151 and 71,332 respectively, but access to antiretroviral therapy (ART) improved and new infections and deaths declined. From 2011-2014 routine HIV testing of TB patients increased from 58.9% to 72.5% and of all TB patients diagnosed with HIV in 2014, 2,803 (72.4%) received ART. The number of multidrug resistant (MDR)-TB cases enrolled for treatment increased almost 3-fold (578 to 1,532) from 2011-2014. The rate of HIV co-infection in MDR and non-MDR TB cases (51/1,532; 3.3% vs 3,774/100,555; 3.8%; OR 0.77, 95% CI 0.7-1.2) was similar in 2014. CONCLUSIONS: The care of TB/HIV co-infected patients have shown sustained improvement in Vietnam. Rising numbers of MDR-TB cases is a concern, but this is not "driven" by HIV co-infection.
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Coinfección/epidemiología , Infecciones por VIH/epidemiología , Tuberculosis Resistente a Múltiples Medicamentos/epidemiología , Adolescente , Adulto , Fármacos Anti-VIH/uso terapéutico , Antituberculosos/uso terapéutico , Coinfección/tratamiento farmacológico , Femenino , Infecciones por VIH/tratamiento farmacológico , Humanos , Masculino , Persona de Mediana Edad , Tuberculosis Resistente a Múltiples Medicamentos/microbiología , Vietnam/epidemiologíaRESUMEN
Tuberculosis (TB) is the leading opportunistic disease and cause of death in patients with HIV infection. In 2013 there were 1.1 million new TB/HIV co-infected cases globally, accounting for 12% of incident TB cases and 360,000 deaths. The Asia-Pacific region, which contributes more than a half of all TB cases worldwide, traditionally reports low TB/HIV co-infection rates. However, routine testing of TB patients for HIV infection is not universally implemented and the estimated prevalence of HIV in new TB cases increased to 6.3% in 2013. Although HIV infection rates have not seen the rapid rise observed in Sub-Saharan Africa, indications are that rates are increasing among specific high-risk groups. This paper reviews the risks of TB exposure and progression to disease, including the risk of TB recurrence, in this vulnerable population. There is urgency to scale up interventions such as intensified TB case-finding, isoniazid preventive therapy, and TB infection control, as well as HIV testing and improved access to antiretroviral treatment. Increased awareness and concerted action is required to reduce TB/HIV co-infection rates in the Asia-Pacific region and to improve the outcomes of people living with HIV.
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Coinfección/epidemiología , Infecciones por VIH/epidemiología , Tuberculosis/epidemiología , Adulto , África del Sur del Sahara , Asia/epidemiología , Niño , Progresión de la Enfermedad , Femenino , Infecciones por VIH/complicaciones , Humanos , Masculino , Prevalencia , Recurrencia , Riesgo , Tuberculosis/complicacionesRESUMEN
OBJECTIVES: To identify patients' beliefs or behaviors related to treatment adherence and to assess association between asthma control and adherence in Asian patients with asthma. METHODS: We conducted a cross-sectional observational study of adult patients with asthma from specialist clinics in six Asian countries. Patients who were deemed by their treating physicians to require a maintenance treatment with an inhaler for at least 1 year were recruited. Patients completed a 12-item questionnaire related to health beliefs and behaviors, the 8-item Morisky Medication Adherence Scale (MMAS-8), the Asthma Control Test (ACT™), and the Standardized Asthma Quality of Life Questionnaire (AQLQ-S). RESULTS: Of the 1054 patients recruited, 99% were current users of inhaled corticosteroids. The mean ACT score was 20.0 ± 4.5 and 64% had well-controlled asthma. The mean MMAS-8 score was 5.5 ± 2.0 and 53% were adherent. Adherence was significantly associated with patients' understanding of the disease and inhaler techniques, and with patients' acceptance of inhaler medicines in terms of benefits, safety, convenience, and cost (p < 0.01 for all). In multivariate analysis, three questions related to patients' acceptance of inhaler medicines remained significantly associated with poor adherence, after adjusting for potential confounders: "I am not sure inhaler type medicines work well" (p = 0.001), "Taking medicines more than once a day is inconvenient" (p = 0.002), and "Sometimes I skip my inhaler to use it over a longer period" (p < 0.001). CONCLUSIONS: Our study showed that patients' acceptance of the benefits, convenience and cost of inhaler medications have a significant impact on treatment adherence in the participating Asian countries.
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Antiasmáticos/administración & dosificación , Asma/tratamiento farmacológico , Asma/psicología , Conocimientos, Actitudes y Práctica en Salud , Cumplimiento de la Medicación/psicología , Adulto , Factores de Edad , Anciano , Antiasmáticos/uso terapéutico , Índice de Masa Corporal , Estudios Transversales , Femenino , Humanos , Masculino , Persona de Mediana Edad , Nebulizadores y Vaporizadores , Aceptación de la Atención de Salud/psicología , Calidad de Vida , Factores Sexuales , Factores SocioeconómicosRESUMEN
Amidino benzimidazoles have been identified as inhibitors of the bacterial KinA/Spo0F two-component system (TCS). Many of these inhibitors exhibit good in vitro antibacterial activity against a variety of susceptible and resistant Gram-positive organisms. The moiety at the 2-position of the benzimidazole was extensively modified. In addition, the regioisomeric benzoxazoles, heterocyclic replacements for the benzimidazole, have been synthesized and their activity against the TCS evaluated.
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Antibacterianos/síntesis química , Bencimidazoles/farmacología , Bacterias Grampositivas/efectos de los fármacos , Proteínas Quinasas , Amidinas/síntesis química , Amidinas/farmacología , Antibacterianos/farmacología , Proteínas Bacterianas/antagonistas & inhibidores , Bencimidazoles/síntesis química , Técnicas Químicas Combinatorias , Bacterias Grampositivas/fisiología , Concentración 50 Inhibidora , Pruebas de Sensibilidad Microbiana , Inhibidores de Proteínas Quinasas , Transducción de Señal/efectos de los fármacosRESUMEN
Uncontrolled cell proliferation is the hallmark of malignant tumours. Thus, the proliferative potential of tumour cells is an important prognostic factor. However, evaluation of the prognostic significance of the expression of proteins involved in regulation of cell proliferation remains controversial. In the present study, expression of Ki-67, PCNA and cyclin D1 was estimated in a group of 89 surgically resected non-small cell lung carcinomas using immunohistochemistry. The results were compared with expression of bcl-2 and p53 and with clinicopathological parameters including patients' survival. Ki-67 and PCNA were found to be moderately and highly expressed in 39% and 44% of the tumours, respectively. There was a strong correlation between Ki67 and PCNA expression. Forty five of 88 tumours (51%) showed overexpression of cyclin D1. Surprisingly, cyclin D1 was mainly localized in the cytoplasm and only a small group of tumours (9/88, 10%) showed nuclear staining as well. Bcl-2 and p53 expression was observed in 69% and 30% of the tumours, respectively. All these markers were found to be independent of clinicopathological parameters, except for Ki-67 and bcl-2 expression, which was associated with squamous cell carcinomas. It is concluded that none of the markers that were studied can be used as an independent prognostic factor, whereas the following combinations of markers may have favourable prognostic value: p53 positivity and low Ki-67 expression, p53 positivity and lack of cyclin D1 expression, bcl-2 positivity and low Ki-67 expression, and lack of cyclin D1 expression and low Ki-67 expression.
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Carcinoma de Pulmón de Células no Pequeñas/metabolismo , Ciclina D1/biosíntesis , Antígeno Ki-67/biosíntesis , Neoplasias Pulmonares/metabolismo , Antígeno Nuclear de Célula en Proliferación/biosíntesis , Proteínas Proto-Oncogénicas c-bcl-2/biosíntesis , Proteína p53 Supresora de Tumor/biosíntesis , Adenocarcinoma/metabolismo , Biomarcadores de Tumor/metabolismo , Neoplasias de los Bronquios/metabolismo , Carcinoma de Pulmón de Células no Pequeñas/diagnóstico , Carcinoma de Pulmón de Células no Pequeñas/mortalidad , Humanos , Inmunohistoquímica , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/mortalidad , Pronóstico , Factores de TiempoRESUMEN
CD44 is a polymorphic family of cell surface glycoproteins that was recently reported to have important role in cell adhesion and migration as well as modulation of cell-matrix interactions. Thus, expression of CD44 has been proposed to be associated with malignant behavior of tumors like invasive growth and formation of metastasis. The expression of CD44s and its v6 isoform (CD44v6) was determined immunohistochemically in 106 lung tumors of various histophenotypes, degrees of differentiation, and clinical stages. The results were compared with the expression of NCAM, CEA, EMA and UP1 and with clinicopathological parameters including patients' survival. CD44s was expressed in all histophenotypes of non-small cell lung carcinomas (NSCLC) with tendency being squamous cell lung carcinoma (SqCC) > bronchioloalveolar adenocarcinoma (BAC) > conventional adenocarcinoma (ConAC) (91, 66.7 and 38.9%, respectively). Almost identical distribution of positivity revealed CD44v6 in all three subgroups of NSCLC mentioned above (91, 66.7 and 36.1%, respectively). In the subgroup of neuroendocrine tumors, CD44s and CD44v6 were restrictedly expressed in small cell lung carcinomas (2/14 tumors), while all 3 typical carcinoids were strongly positive for these markers. Expression of NCAM and CEA was significantly higher in adenocarcinoma subgroup than those in SqCC subgroup (45.7 and 75% vs. 14.8 and 39%, respectively). NCAM expression was also significantly different in BACs and in ConACs (69.2 vs. 36.4%, p < 0.05). The expression of CD44 was related to the differentiation of SqCC. The carcinomas with keratinization were CD44 positive. Adenocarcinomas producing mucin were CD44 negative. The expression of CD44, NCAM, CEA, EMA and UP1 did not correlate with lymph node metastasis and disease stage. CD44V6 was the only marker that its expression was closely related to patients' survival. The absence CD44v6 but not CD44s in NSCLC group was associated with significantly longer survival of patients compared to patients with CD44v6 positive tumors. This difference was even higher in tumors negative for CD44v6 and simultaneously NCAM and/or CEA positive. The data of this study suggest that CD44v6 might be an independent prognostic factor in NSCLC. Moreover, our data give another evidence of diverse role of CD44 in the differentiation and progression of non-small cell lung carcinomas and neuroendocrine carcinomas of the lung.
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Empalme Alternativo , Antígeno Carcinoembrionario/biosíntesis , Receptores de Hialuranos/biosíntesis , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/metabolismo , Mucina-1/biosíntesis , Moléculas de Adhesión de Célula Nerviosa/biosíntesis , Biosíntesis de Proteínas , Uteroglobina , Adenocarcinoma/metabolismo , Adenocarcinoma/mortalidad , Biomarcadores de Tumor , Carcinoma de Pulmón de Células no Pequeñas/metabolismo , Carcinoma de Pulmón de Células no Pequeñas/mortalidad , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/mortalidad , Regulación hacia Abajo , Humanos , Receptores de Hialuranos/genética , Inmunohistoquímica , Neoplasias Pulmonares/mortalidad , Metástasis Linfática , Mucinas/metabolismo , Pronóstico , Isoformas de Proteínas , Factores de TiempoAsunto(s)
Antimaláricos/uso terapéutico , Artemisininas , Azitromicina/uso terapéutico , Malaria Falciparum/tratamiento farmacológico , Sesquiterpenos/uso terapéutico , Animales , Antimaláricos/administración & dosificación , Artesunato , Azitromicina/administración & dosificación , Países en Desarrollo , Esquema de Medicación , Humanos , Malaria Falciparum/prevención & control , Masculino , Proyectos Piloto , Recurrencia , Sesquiterpenos/administración & dosificación , Resultado del Tratamiento , VietnamRESUMEN
A series of isoindolo[2,1-a]- and pyrrolo[1,2-a]quinolines were designed and synthesized for DNA-gyrase and topoisomerase-II inhibition studies. Some of the compounds showed significant activity against the enzymes.
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Inhibidores Enzimáticos/síntesis química , Indoles/síntesis química , Pirroles/síntesis química , Quinolinas/síntesis química , Inhibidores de Topoisomerasa II , Bacterias/enzimología , Inhibidores Enzimáticos/química , Inhibidores Enzimáticos/farmacología , Humanos , Indoles/química , Indoles/farmacología , Pirroles/química , Pirroles/farmacología , Quinolinas/química , Quinolinas/farmacología , Relación Estructura-ActividadRESUMEN
The synthesis and inhibitory activity against DNA gyrase of a series of diphenic acid monohydroxamides 4a-f are described. A protocol of two biological assays showed conclusively that inhibition occurs specifically at the DNA-DNA gyrase complex and is not attributable to nonspecific inhibition. In the enzyme assays, 4c was potent as the prototypical quinolone, nalidixic acid (1), with an IC50 value of 58.3 micrograms/mL compared to 52 micrograms/mL for 1. MIC activity against bacterial strains showed a systematic drop for all compounds relative to 1. For compounds 4c-e, the addition of PMBN produced dramatic increases in MIC activity indicating that activity is likely to be related to membrane transport. Molecular modeling of 4a indicates that the diphenic acid monohydroxamides can bind to the DNA-DNA gyrase complex in a similar fashion as that hypothesized for the quinolone series according to the hypothesis suggested by Shen et al. but may not self-associate by pi-pi stacking. In contrast to the quinolone series, as the diphenic acid monohydroxamides are shown by molecular mechanics minimizations to be nonplanar, they may present novel approaches for chemotherapeutic intervention with a potential for decreased side effects.
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Antibacterianos/síntesis química , Compuestos de Bifenilo/química , Inhibidores Enzimáticos/síntesis química , Ácidos Hidroxámicos/química , Inhibidores de Topoisomerasa II , Antibacterianos/farmacología , Compuestos de Bifenilo/farmacología , Inhibidores Enzimáticos/farmacología , Escherichia coli/enzimología , Ácidos Hidroxámicos/farmacología , Modelos Químicos , Modelos MolecularesRESUMEN
A series of 2-substituted benzofuran hydroxyamic acids were synthesized as rigid analogs of simple (benzyloxy)phenyl hydroxamates, evaluated for their in vitro and in vivo 5-lipoxygenase activity and found to be potent inhibitors of the enzyme. Substituents which enhanced lipophilicity near the 2-position of the benzofuran nucleus increased inhibitor potency but reduced oral activity. Incorporation of small polar substituents such as methoxymethylene, hydroxymethylene, and amino (urea) on the acyl group led to more consistent oral activity. The most potent inhibitors of this series in vitro were N-hydroxy-N-[1-(2-phenyl-5-benzofuranyl)-ethyl]furancarboxamide (12) and methyl 5-[N-hydroxy-N-[1-(2-(3,4,5-trimethoxyphenyl)-5-benzofuranyl]ethyl]-5- oxopentanoate (17), both with IC50 values of 40 nM, and in vivo the most potent compound was N-hydroxy-N-[1-(2-phenyl-5-benzofuranyl)ethyl]urea, 20, with an ED50 = 10.3 mg/kg.
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Benzofuranos/síntesis química , Inhibidores de la Lipooxigenasa , Animales , Benzofuranos/farmacología , Masculino , Ratones , Estructura Molecular , Peritonitis/inducido químicamente , Relación Estructura-Actividad , ZimosanRESUMEN
Two series of novel bishydroxamic acids 2 and 3 (types A and B) were synthesized and tested for inhibition of 5-lipoxygenase from rat basophile leukemia (RBL) cells. Both series were potent inhibitors of the isolated enzyme but only the type B reverse hydroxamic acids possessed significant oral activity. The most potent compound, orally, was 3a, [IC50 = 270 nM; ED50 = 1.86 mg/kg], which compares favorably with the clinically useful 5-lipoxygenase inhibitor, zileuton. Unlike known hydroxamic acid inhibitors, the oral activity in this series appears to be associated with the second hydroxamic acid group. The corresponding monohydroxamic acids retained inhibitor potency, in vitro, with reduced oral activity in a mouse zymosan peritonitis model. Compound 4e [IC50 = 7 nM], a monohydroxamic acid derivative related to 3a, is among the most potent inhibitors of the isolated enzyme yet to be reported.