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1.
J Surg Case Rep ; 2023(8): rjad457, 2023 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-37564057

RESUMEN

Orbital infection is a rare complication of odontogenic infections, mostly originating from maxillary teeth. In our case, we present one of the unusual routes by which an odontogenic infection of a lower molar tooth has spread into the orbit. A 67-year-old uncontrolled diabetic patient was referred to our hospital with a complaint of a swollen right masseteric region and orbital infection following a dental procedure on the right mandibular third molar. Computed tomography scan and magnetic resonance imaging showed multiple abscesses localized in the masseteric and infratemporal spaces, extending into the orbital cavity through bony erosion in the lateral orbital with no sinus involvement. Improper treatment and poorly controlled diabetes resulted in the extensive spread of the infection. Clinical and radiological reevaluation has played a major role in the management of our case by elucidating the route of infection and localizing abscess foci accurately.

2.
Neurosurgery ; 92(6): 1183-1191, 2023 06 01.
Artículo en Inglés | MEDLINE | ID: mdl-36735514

RESUMEN

BACKGROUND: The increase in use of targeted systemic therapies in cancer treatments has catalyzed the importance of identifying patient- and tumor-specific somatic mutations, especially regarding metastatic disease. Mutations found to be most prevalent in patients with metastatic breast cancer include TP53, PI3K, and CDH1. OBJECTIVE: To determine the incidence of somatic mutations in patients with metastatic breast cancer to the spine (MBCS). To determine if a difference exists in overall survival (OS), progression-free survival, and progression of motor symptoms between patients who do or do not undergo targeted systemic therapy after treatment for MBCS. METHODS: This is a retrospective study of patients with MBCS. Review of gene sequencing reports was conducted to calculate the prevalence of various somatic gene mutations within this population. Those patients who then underwent treatment (surgery/radiation) for their diagnosis of MBCS between 2010 and 2020 were subcategorized. The use of targeted systemic therapy in the post-treatment period was identified, and post-treatment OS, progression-free survival, and progression of motor deficits were calculated for this subpopulation. RESULTS: A total of 131 patients were included in the final analysis with 56% of patients found to have a PI3K mutation. Patients who received targeted systemic therapies were found to have a significantly longer OS compared with those who did not receive targeted systemic therapies. CONCLUSION: The results of this study demonstrate that there is an increased prevalence of PI3K mutations in patients with MBCS and there are a significant survival benefit and delay in progression of motor symptoms associated with using targeted systemic therapies for adjuvant treatment.


Asunto(s)
Neoplasias de la Mama , Humanos , Femenino , Neoplasias de la Mama/genética , Neoplasias de la Mama/terapia , Neoplasias de la Mama/patología , Estudios Retrospectivos , Incidencia , Mutación/genética , Fosfatidilinositol 3-Quinasas/genética
3.
Int Dent J ; 73(2): 296-301, 2023 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-36030120

RESUMEN

INTRODUCTION: The delay in seeking dental treatment is a universal health problem, with a reported prevalence as high as 98%. It is a critical feature not only in planning management but also in the final treatment outcome. AIM: This study aimed to determine the reasons for the delay in seeking treatment for dental caries amongst patients attending public dental clinics in Dar es Salaam, Tanzania. METHODOLOGY: This was a cross-sectional study carried out in 5 public hospitals in Dar es Salaam, Tanzania. It included 315 adult patients who had dental caries. Data were collected using a questionnaire that included questions regarding reasons for the delay in seeking care for dental caries. Data were analysed using the SPSS computer software version 26. A one-way analysis of variance was used to assess the association between variables, and the significance level was set at P < .05. RESULTS: A majority (n = 244, 77.5%) of the participants delayed seeking dental care upon noting a problem in their teeth. However, the association between the sociodemographic characteristics of the participants and delay in seeking dental care was statistically insignificant (P > .05). The most common reason given by the participants who delayed seeking dental care for their decayed teeth included self-negligence (n = 184, 75.4%), the practice of self-medication (n = 164, 67.2%), and ignorance (n = 110, 45.1%). CONCLUSIONS: The majority of patients experiencing dental caries seek dental care very late. Delay in seeking dental care is not dependent on sociodemographic characteristics of individuals. Self-negligence, the practice of self­medication, and ignorance are the major reasons for the delay.


Asunto(s)
Caries Dental , Diente , Adulto , Humanos , Caries Dental/epidemiología , Tanzanía/epidemiología , Estudios Transversales , Resultado del Tratamiento
4.
Br J Cancer ; 122(7): 1005-1013, 2020 03.
Artículo en Inglés | MEDLINE | ID: mdl-32025027

RESUMEN

BACKGROUND: Ibrutinib is a Bruton's tyrosine kinase (BTK) and interleukin-2-inducible kinase (ITK) inhibitor used for treating chronic lymphocytic leukaemia (CLL) and other cancers. Although ibrutinib is known to inhibit the growth of breast cancer cell growth in vitro, its impact on the treatment and metastasis of breast cancer is unclear. METHODS: Using an orthotopic mouse breast cancer model, we show that ibrutinib inhibits the progression and metastasis of breast cancer. RESULTS: Ibrutinib inhibited proliferation of cancer cells in vitro, and Ibrutinib-treated mice displayed significantly lower tumour burdens and metastasis compared to controls. Furthermore, the spleens and tumours from Ibrutinib-treated mice contained more mature DCs and lower numbers of myeloid-derived suppressor cells (MDSCs), which promote disease progression and are linked to poor prognosis. We also confirmed that ex vivo treatment of MDSCs with ibrutinib switched their phenotype to mature DCs and significantly enhanced MHCII expression. Further, ibrutinib treatment promoted T cell proliferation and effector functions leading to the induction of antitumour TH1 and CTL immune responses. CONCLUSIONS: Ibrutinib inhibits tumour development and metastasis in breast cancer by promoting the development of mature DCs from MDSCs and hence could be a novel therapeutic agent for the treatment of breast cancer.


Asunto(s)
Adenina/análogos & derivados , Neoplasias de la Mama/tratamiento farmacológico , Células Dendríticas/metabolismo , Células Supresoras de Origen Mieloide/metabolismo , Metástasis de la Neoplasia/tratamiento farmacológico , Piperidinas/uso terapéutico , Adenina/farmacología , Adenina/uso terapéutico , Animales , Neoplasias de la Mama/patología , Progresión de la Enfermedad , Femenino , Humanos , Ratones , Piperidinas/farmacología
5.
Int J Cancer ; 146(6): 1717-1729, 2020 03 15.
Artículo en Inglés | MEDLINE | ID: mdl-31709529

RESUMEN

Cancers of the oral cavity remain the sixth most diagnosed cancer worldwide, with high rates of recurrence and mortality. We determined the role of STAT1 during oral carcinogenesis using two orthotopic models in mice genetically deficient for Stat1. Metastatic (LY2) and nonmetastatic (B4B8) head and neck squamous cell carcinoma (HNSCC) cell lines were injected into the oral cavity of Stat1 deficient (Stat1-/- ) and Stat1 competent (Stat1+/+ ) mice. Stat1-/- mice displayed increased tumor growth and metastasis compared to Stat1+/+ mice. Mechanistically, Stat1-/- mice displayed impaired CD4+ and CD8+ T-cell expansion compared to Stat1+/+ mice. This was associated with enhanced T-cell exhaustion, and severely attenuated T-cell antitumor effector responses including reduced expression of IFN-γ and perforin at the tumor site. Interestingly, tumor necrosis factor (TNF)-α production by T cells in tumor-bearing mice was suppressed by Stat1 deficiency. This deficiency in T-cell expansion and functional responses in mice was linked to PD-1 and CD69 overexpression in T cells of Stat1-/- mice. In contrast, we observed increased accumulation of CD11b+ Ly6G+ myeloid derived suppressor cells in tumors, draining lymph nodes, spleens and bone marrow of tumor-bearing Stat1-/- mice, resulting in a protumorigenic microenvironment. Our data demonstrates that STAT1 is an essential mediator of the antitumor response through inhibition of myeloid derived suppressor cell accumulation and promotion of T-cell mediated immune responses in murine head and neck squamous cell carcinoma. Selective induction of STAT1 phosphorylation in HNSCC patients could potentially improve oral tumor outcomes and response to therapy.


Asunto(s)
Inmunomodulación , Células Supresoras de Origen Mieloide/inmunología , Células Supresoras de Origen Mieloide/metabolismo , Factor de Transcripción STAT1/metabolismo , Carcinoma de Células Escamosas de Cabeza y Cuello/etiología , Carcinoma de Células Escamosas de Cabeza y Cuello/metabolismo , Linfocitos T/inmunología , Linfocitos T/metabolismo , Animales , Línea Celular Tumoral , Modelos Animales de Enfermedad , Progresión de la Enfermedad , Femenino , Humanos , Ganglios Linfáticos/patología , Masculino , Ratones , Ratones Noqueados , Metástasis de la Neoplasia , Estadificación de Neoplasias , Factor de Transcripción STAT1/deficiencia , Carcinoma de Células Escamosas de Cabeza y Cuello/patología , Subgrupos de Linfocitos T/inmunología , Subgrupos de Linfocitos T/metabolismo , Microambiente Tumoral
6.
Data Brief ; 26: 104394, 2019 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-31516941

RESUMEN

The provision of suitable incubation environments is vital for successful implementation of bio self-healing concrete (bio-concrete). We investigated the effect of soil incubation to examine if the self-healing process can be activated in comparison with the conventional incubation environment (water). The data was collected from laboratory-scale experiments conducted on mortar specimens. The mortar was impregnated with Bacillus subtilis and this bacteria was encapsulated in calcium alginate for protection from the production process. The mortar specimens were mechanically cracked and then incubated within fine-grained fully saturated natural soil for about 4 weeks. The cracks were inspected before and after incubation by light microscopy to evaluate the healing ratio. The mineral precipitations on crack surfaces were examined by Scanning Electron Microscope (SEM) and Energy Dispersive X-Ray Spectrometry (EDX). The data reflects the efficiency of bio-concrete for certain structures such as tunnels and deep foundation, where concrete elements are exposed to ground conditions.

7.
Future Med Chem ; 11(15): 1999-2018, 2019 08.
Artículo en Inglés | MEDLINE | ID: mdl-31390889

RESUMEN

Parasitic infections are responsible for significant morbidity and mortality throughout the world. Management strategies rely primarily on antiparasitic drugs that have side effects and risk of drug resistance. Therefore, novel strategies are needed for treatment of parasitic infections. Host-directed therapy (HDT) is a viable alternative, which targets host pathways responsible for parasite invasion/survival/pathogenicity. Recent innovative combinations of genomics, proteomics and computational biology approaches have led to discovery of several host pathways that could be promising targets for HDT for treating parasitic infections. Herein, we review major advances in HDT for parasitic disease with regard to core regulatory pathways and their interactions.


Asunto(s)
Antiinfecciosos/uso terapéutico , Enfermedades Parasitarias/tratamiento farmacológico , Antiinfecciosos/farmacología , Anticuerpos Monoclonales/uso terapéutico , Cannabinoides/farmacología , Cannabinoides/uso terapéutico , Enfermedad de Chagas/tratamiento farmacológico , Enfermedad de Chagas/patología , Humanos , Leishmaniasis/tratamiento farmacológico , Leishmaniasis/inmunología , Leishmaniasis/patología , Enfermedades Parasitarias/inmunología , Enfermedades Parasitarias/patología , Linfocitos T/citología , Linfocitos T/efectos de los fármacos , Linfocitos T/inmunología , Toxoplasmosis/tratamiento farmacológico , Toxoplasmosis/patología , Trypanosoma cruzi/efectos de los fármacos , Trypanosoma cruzi/fisiología
8.
Infect Immun ; 87(8)2019 08.
Artículo en Inglés | MEDLINE | ID: mdl-31182615

RESUMEN

CD4+ T helper 1 (Th1) cells producing interferon gamma (IFN-γ) are critical for the resolution of visceral leishmaniasis (VL). MicroRNA 155 (miR155) promotes CD4+ Th1 responses and IFN-γ production by targeting suppressor of cytokine signaling-1 (SOCS1) and Src homology-2 domain-containing inositol 5-phosphatase 1 (SHIP-1) and therefore could play a role in the resolution of VL. To determine the role of miR155 in VL, we monitored the course of Leishmania donovani infection in miR155 knockout (miR155KO) and wild-type (WT) C57BL/6 mice. miR155KO mice displayed significantly higher liver and spleen parasite loads than WT controls and showed impaired hepatic granuloma formation. However, parasite growth eventually declined in miR155KO mice, suggesting the induction of a compensatory miR155-independent antileishmanial pathway. Leishmania antigen-stimulated splenocytes from miR155KO mice produced significantly lower levels of Th1-associated IFN-γ than controls. Interestingly, at later time points, levels of Th2-associated interleukin-4 (IL-4) and IL-10 were also lower in miR155KO splenocyte supernatants than in WT mice. On the other hand, miR155KO mice displayed significantly higher levels of IFN-γ, iNOS, and TNF-α gene transcripts in their livers than WT mice, indicating that distinct organ-specific antiparasitic mechanisms were involved in control of L. donovani infection in miR155KO mice. Throughout the course of infection, organs of miR155KO mice showed significantly more PDL1-expressing Ly6Chi inflammatory monocytes than WT mice. Conversely, blockade of Ly6Chi inflammatory monocyte recruitment in miR155KO mice significantly reduced parasitic loads, indicating that these cells contributed to disease susceptibility. In conclusion, we found that miR155 contributes to the control of L. donovani but is not essential for infection resolution.


Asunto(s)
Leishmania donovani , Leishmaniasis Visceral/inmunología , MicroARNs/fisiología , Animales , Granuloma/etiología , Interferón gamma/fisiología , Ratones , Ratones Endogámicos C57BL , Monocitos/fisiología , Linfocitos T/inmunología , Factor de Necrosis Tumoral alfa/fisiología
9.
J Infect Dis ; 219(4): 599-608, 2019 01 29.
Artículo en Inglés | MEDLINE | ID: mdl-30239895

RESUMEN

Background: New drugs are needed for leishmaniasis because current treatments such as pentavalent antimonials are toxic and require prolonged administration, leading to poor patient compliance. Ibrutinib is an anticancer drug known to modulate T-helper type 1 (Th1)/Th2 responses and has the potential to regulate immunity against infectious disease. Methods: In this study, we evaluated the efficacy of oral ibrutinib as a host-targeted treatment for visceral leishmaniasis (VL) caused by Leishmania donovani using an experimental mouse model. Results: We found that oral ibrutinib was significantly more effective than the pentavalent antimonial sodium stibogluconate (70 mg/kg) for the treatment of VL caused by L. donovani. Ibrutinib treatment increased the number of interleukin 4- and interferon γ-producing natural killer T cells in the liver and spleen and enhanced granuloma formation in the liver. Further, ibrutinib treatment reduced the influx of Ly6Chi inflammatory monocytes, which mediate susceptibility to L. donovani. Finally, ibrutinib treatment was associated with the increased production of the cytokines interferon γ, tumor necrosis factor α, interleukin 4, and interleukin 13 in the liver and spleen, which are associated with protection against L. donovani. Conclusions: Our findings show that oral ibrutinib is highly effective for the treatment of VL caused by L. donovani and mediates its antileishmanial activity by promoting host immunity. Therefore, ibrutinib could be a novel host-targeted drug for the treatment of VL.


Asunto(s)
Factores Inmunológicos/administración & dosificación , Leishmania donovani/crecimiento & desarrollo , Leishmaniasis Visceral/tratamiento farmacológico , Inhibidores de Proteínas Quinasas/administración & dosificación , Pirazoles/administración & dosificación , Pirimidinas/administración & dosificación , Adenina/análogos & derivados , Administración Oral , Animales , Citocinas/metabolismo , Modelos Animales de Enfermedad , Femenino , Inmunidad Celular , Ratones , Ratones Endogámicos BALB C , Piperidinas , Resultado del Tratamiento
10.
Front Microbiol ; 9: 2655, 2018.
Artículo en Inglés | MEDLINE | ID: mdl-30555425

RESUMEN

The neglected tropical diseases (NTDs) caused by protozoan parasites are responsible for significant morbidity and mortality worldwide. Current treatments using anti-parasitic drugs are toxic and prolonged with poor patient compliance. In addition, emergence of drug-resistant parasites is increasing worldwide. Hence, there is a need for safer and better therapeutics for these infections. Host-directed therapy using drugs that target host pathways required for pathogen survival or its clearance is a promising approach for treating infections. This review will give a summary of the current status and advances of host-targeted therapies for treating NTDs caused by protozoa.

11.
J Pediatr Nurs ; 31(3): 293-8, 2016.
Artículo en Inglés | MEDLINE | ID: mdl-26850937

RESUMEN

UNLABELLED: The purpose of the current study was to explore factors related to the intention of parents from the Muslim Arab ethnic minority in Israel to vaccinate their children against influenza, using the Health Belief Model (HBM). DESIGN AND METHODS: This study is a cross sectional quantitative study. A convenience sample of 200 parents of children aged 12 and younger completed a questionnaire based on the HBM. RESULTS: Perceived susceptibility, severity, benefits, and barriers predicted 88% of parents' intention to vaccinate their children. Parents who vaccinated their children in the past year were younger and had fewer children. Community nurses and physicians were identified as important cues to action. CONCLUSIONS: The HBM components predicted a high percentage of parents' intention to vaccinate their children PRACTICE IMPLICATIONS: Interventions to raise vaccination coverage rates among children belonging to an ethnic minority of Israeli Muslim Arabs should begin on the micro level of the parent-health care professional encounter.


Asunto(s)
Conocimientos, Actitudes y Práctica en Salud/etnología , Vacunas contra la Influenza/administración & dosificación , Gripe Humana/prevención & control , Intención , Aceptación de la Atención de Salud/etnología , Árabes/psicología , Niño , Preescolar , Estudios Transversales , Estudios de Evaluación como Asunto , Femenino , Humanos , Islamismo/psicología , Israel , Modelos Lineales , Masculino , Análisis Multivariante , Padres , Factores de Riesgo , Vacunación/psicología
12.
Med Mycol ; 52(4): 333-41, 2014 May.
Artículo en Inglés | MEDLINE | ID: mdl-24713404

RESUMEN

Candida albicans can cause candidemia in neutropenic and critically ill patients and oropharyngeal candidiasis in human immunodeficiency virus (HIV)-positive patients with low CD4(+) counts. Because all patients at risk do not develop Candida infections, it is possible that a patient's genetic background might play a role in his or her susceptibility to infection. Autophagy mediates pathogen clearance and modulation of inflammation. Our aim was to assess the effect of genetic variations in the ATG16L1 and IRGM autophagy genes on the susceptibility of patients with candidemia and oropharyngeal candidiasis. We assessed genetic variations in the ATG16L1 and IRGM genes in a cohort of candidemia patients of both African and European origin. In addition, we evaluated the effect of these polymorphisms on the susceptibility to oropharyngeal candidiasis of an HIV-positive cohort from Tanzania. Functional studies have been performed to assess the effect of the ATG16L1 and IRGM genetic variants on both in vitro and in vivo cytokine production. The results indicate that ATG16L1 variants modulate production of tumor necrosis factor-alpha, but not other cytokines, while no effects were seen in the presence of IRGM polymorphisms. In addition, no significant associations between the single-nucleotide polymorphisms in the ATG16L1 and IRGM genetic variants and the incidence of candidemia or oropharyngeal candidiasis were identified. Despite moderate effects on the modulation of proinflammatory cytokine production, genetic variation in the autophagy genes ATG16L1 and IRGM has a minor impact on the susceptibility to both mucosal and systemic Candida infections.


Asunto(s)
Autofagia , Candidiasis/genética , Candidiasis/inmunología , Proteínas Portadoras/genética , Proteínas de Unión al GTP/genética , Predisposición Genética a la Enfermedad , África , Proteínas Relacionadas con la Autofagia , Estudios de Cohortes , Citocinas/metabolismo , Europa (Continente) , Humanos , Polimorfismo de Nucleótido Simple , Medición de Riesgo
13.
J Acquir Immune Defic Syndr ; 55(1): 87-94, 2010 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-20577092

RESUMEN

BACKGROUND: The occurrence of oropharyngeal candidiasis (OPC) in combination with HIV disease progression is a very common phenomenon. However, not all HIV-infected patients develop OPC, even when they progress to low CD4 T-cell counts. Because T-cell immunity is defective in AIDS, the innate defence mechanisms are likely to have a central role in antifungal immunity in these patients. We investigated whether genetic variations in the innate immune genes DECTIN-1, TLR2, TLR4, TIRAP, and CASPASE-12 are associated with the presence of OPC in HIV-infected subjects from East Africa. METHODS: A total of 225 HIV patients were genotyped for several single nucleotide polymorphisms (SNPs), and this was correlated with the occurrence of OPC in these patients. In addition, primary immune cells obtained from individuals with different genotypes were stimulated with Candida albicans, and cytokine production was measured. RESULTS: The analysis revealed that no significant differences in the polymorphism frequencies could be observed, although a tendency toward a protective effect on OPC of the DECTIN-1 I223S SNP was apparent. Furthermore, interferon gamma production capacity was markedly lower in cells bearing the DECTIN-1 SNP I223S. It could also be demonstrated that the 223S mutated form of the DECTIN-1 gene exhibits a lower capacity to bind zymosan. CONCLUSIONS: These data demonstrate that common polymorphisms of TLR2, TLR4, TIRAP, and CASPASE-12 do not influence susceptibility to OPC in HIV-infected patients in East Africa but suggest an immunomodulatory effect of the I223S SNP on dectin-1 function and possibly the susceptibility to OPC in HIV patients.


Asunto(s)
Candidiasis Bucal/epidemiología , Candidiasis Bucal/inmunología , Variación Genética , Infecciones por VIH/complicaciones , Inmunidad Innata/genética , África , Candida albicans/inmunología , Candida albicans/aislamiento & purificación , Citocinas/metabolismo , Genes Fúngicos , Humanos , Leucocitos Mononucleares/inmunología , Leucocitos Mononucleares/microbiología
14.
Clin Infect Dis ; 47(10): 1270-6, 2008 Nov 15.
Artículo en Inglés | MEDLINE | ID: mdl-18840077

RESUMEN

BACKGROUND: Oropharyngeal candidiasis is the most common opportunistic infection affecting patients with human immunodeficiency virus (HIV) infection. Because of convenience, cost, and reluctance to complicate antiretroviral treatment regimens, single-dose fluconazole may be a favorable regimen for treatment of moderate to severe oropharyngeal candidiasis. We conducted a prospective, randomized, double-blind, placebo-controlled trial to compare the clinical and mycological responses, relapse rates, and safety of a single 750-mg dose and a 14-day course of treatment with fluconazole. METHODS: A total of 220 HIV-infected patients with clinical and mycological evidence of oropharyngeal candidiasis were randomly assigned in a 1:1 ratio to receive either a 750-mg single dose of orally administered fluconazole (110 patients) or 150 mg of orally administered fluconazole once per day for 2 weeks (110 patients). The primary efficacy analysis was based on clinical and mycological responses at the end of treatment. Secondary parameters were safety and relapse rate. RESULTS: Single-dose fluconazole was equivalent to a 14-day course of fluconazole in achieving clinical and mycological cure, with clinical cure rates of 94.5% and 95.5%, respectively (odds ratio, 0.825; 95% confidence interval, 0.244-2.789; P= .99), and mycological cure rates of 84.5% and 75.5%, respectively (odds ratio, 1.780; 95% confidence interval, 0.906-3.496; P= .129). Drug-related adverse events were uncommon and were not different between the treatment groups. CONCLUSION: A single dose of 750 mg of fluconazole was safe, well tolerated, and as effective as the standard 14-day fluconazole therapy in patients with HIV infection and acquired immunodeficiency syndrome who had oropharyngeal candidiasis coinfection.


Asunto(s)
Antifúngicos/uso terapéutico , Candidiasis Bucal/tratamiento farmacológico , Fluconazol/uso terapéutico , Infecciones por VIH/complicaciones , Adulto , Anciano , Antifúngicos/administración & dosificación , Antifúngicos/efectos adversos , Método Doble Ciego , Femenino , Fluconazol/administración & dosificación , Fluconazol/efectos adversos , Humanos , Masculino , Persona de Mediana Edad , Orofaringe/microbiología , Placebos/administración & dosificación , Estudios Prospectivos , Resultado del Tratamiento
15.
BMC Microbiol ; 8: 135, 2008 Aug 12.
Artículo en Inglés | MEDLINE | ID: mdl-18694525

RESUMEN

BACKGROUND: In Tanzania, little is known on the species distribution and antifungal susceptibility profiles of yeast isolates from HIV-infected patients with primary and recurrent oropharyngeal candidiasis. METHODS: A total of 296 clinical oral yeasts were isolated from 292 HIV-infected patients with oropharyngeal candidiasis at the Muhimbili National Hospital, Dar es Salaam, Tanzania. Identification of the yeasts was performed using standard phenotypic methods. Antifungal susceptibility to fluconazole, itraconazole, miconazole, clotrimazole, amphotericin B and nystatin was assessed using a broth microdilution format according to the guidelines of the Clinical and Laboratory Standard Institute (CLSI; M27-A2). RESULTS: Candida albicans was the most frequently isolated species from 250 (84.5%) patients followed by C. glabrata from 20 (6.8%) patients, and C. krusei from 10 (3.4%) patients. There was no observed significant difference in species distribution between patients with primary and recurrent oropharyngeal candidiasis, but isolates cultured from patients previously treated were significantly less susceptible to the azole compounds compared to those cultured from antifungal naïve patients. CONCLUSION: C. albicans was the most frequently isolated species from patients with oropharyngeal candidiasis. Oral yeast isolates from Tanzania had high level susceptibility to the antifungal agents tested. Recurrent oropharyngeal candidiasis and previous antifungal therapy significantly correlated with reduced susceptibility to azoles antifungal agents.


Asunto(s)
Infecciones Oportunistas Relacionadas con el SIDA/microbiología , Antifúngicos/farmacología , Candidiasis Bucal/microbiología , Orofaringe/microbiología , Levaduras/efectos de los fármacos , Levaduras/aislamiento & purificación , Infecciones Oportunistas Relacionadas con el SIDA/tratamiento farmacológico , Infecciones Oportunistas Relacionadas con el SIDA/epidemiología , Infecciones Oportunistas Relacionadas con el SIDA/patología , Adulto , Candida albicans/efectos de los fármacos , Candida albicans/aislamiento & purificación , Candidiasis Bucal/epidemiología , Candidiasis Bucal/patología , Femenino , Humanos , Masculino , Pruebas de Sensibilidad Microbiana , Recurrencia , Tanzanía/epidemiología
16.
BMC Oral Health ; 8: 12, 2008 Apr 30.
Artículo en Inglés | MEDLINE | ID: mdl-18447929

RESUMEN

BACKGROUND: Human bites in the maxillofacial region compromise function and aesthetics, resulting in social and psychological effects. There is paucity of information regarding human bite injuries in Tanzania. The aim of the study was to assess the occurrence, treatment modalities and prognosis of human bite injuries in the oro-facial region at the Muhimbili National Hospital Dar es Salaam, Tanzania. METHODS: In a prospective study the details of patients with human bite injuries in the oro-facial region who attended at the Department of Oral and Maxillofacial Surgery of the Muhimbili National Hospital between January 2001 and December 2005 were recorded. Data included information on age, sex, site, duration of the injury at the time of reporting to hospital, reasons, details of treatment offered and outcome after treatment. RESULTS: A total of 33 patients, 13 males and 20 females aged between 12 and 49 years with human bite injuries in the oro-facial region were treated. Thirty patients presented with clean uninfected wounds while 3 had infected wounds. The most (45.5%) frequently affected site was the lower lip. Treatment offered included thorough surgical cleansing with adequate surgical debridement and primary suturing. Tetanus prophylaxis and a course of broad-spectrum antibiotics were given to all the patients. In 90% of the 30 patients who were treated by suturing, the healing was uneventful with only 10% experiencing wound infection or necrosis. Three patients who presented with wounds that had signs of infection were treated by surgical cleansing with debridement, antibiotics and daily dressing followed by delayed primary suturing. CONCLUSION: Most of the human bite injuries in the oro-facial region were due to social conflicts. Although generally considered to be dirty or contaminated they could be successfully treated by surgical cleansing and primary suture with a favourable outcome. Management of such injuries often need multidisciplinary approach.

17.
Basic Clin Pharmacol Toxicol ; 102(6): 515-26, 2008 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-18331392

RESUMEN

HIV-infected patients in sub-Saharan countries highly depend on traditional medicines for the treatment of opportunistic oral infections as candidiasis. Previous investigations on antifungal activity of medicinal plant extracts utilized by traditional healers in Tanzania have revealed 12 extracts with potent antifungal activity. Although the plants may be good candidates for new treatment opportunities, they can be toxic or genotoxic and could cause pharmacokinetic interactions when used concomitantly with antiretroviral agents. Therefore, we investigated the cytotoxicity, genotoxicity and cytochrome P450 interaction potential of these medicinal plants. Cytotoxicity was tested by Hoechst 33342, Alamar Blue, calcein-AM, glutathione depletion and O(2)-consumption assays and genotoxicity by a Vitotox assay. Competition of the 12 extracts on substrate metabolism by CYP3A4, 2C9, 2C19 and 2D6 was tested with high-throughput CYP inhibition screening. Pregnane X receptor (PXR) activation was tested using Chinese hamster ovary cell lines expressing human PXR. Herbal extracts inducing high human PXR activation were tested for enhanced CYP3A4 mRNA levels with quantitative polymerase chain reaction. Genotoxicity was found for Jatropha multifida, Sterculia africana and Spirostachys africana. All plant extracts showed high cytotoxic effects in almost all tests. Potent competition with CYP3A4, 2D6, 2C9 and 2C19 was found for 75% of the herbal extracts. Spirostachys africana did not affect CYP2D6 and for S. africana and Turraea holstii no effect on CYP2D6 and CYP3A4 (DBF) was found. Nine plant extracts showed significant activation of human PXR, but only Agaura salicifolia, Turraea holstii and S. africana significantly induced CYP3A4 mRNA levels. These results indicate the possibility of potential medicinal plant-antiretroviral interactions.


Asunto(s)
Antifúngicos/farmacología , Sistema Enzimático del Citocromo P-450/metabolismo , Medicinas Tradicionales Africanas , Mutágenos/farmacología , Extractos Vegetales/farmacología , Animales , Antifúngicos/metabolismo , Células CHO , Supervivencia Celular/efectos de los fármacos , Cricetinae , Cricetulus , Sistema Enzimático del Citocromo P-450/genética , ADN Bacteriano/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Inducción Enzimática , Etnofarmacología , Regulación Enzimológica de la Expresión Génica/efectos de los fármacos , Genes Bacterianos/efectos de los fármacos , Genes Bacterianos/genética , Células HeLa/efectos de los fármacos , Células HeLa/enzimología , Hepatocitos/efectos de los fármacos , Hepatocitos/enzimología , Humanos , Pruebas de Sensibilidad Microbiana , Microsomas Hepáticos/efectos de los fármacos , Microsomas Hepáticos/metabolismo , Mitocondrias Hepáticas/efectos de los fármacos , Mitocondrias Hepáticas/metabolismo , Pruebas de Mutagenicidad/métodos , Mutágenos/clasificación , Mutágenos/metabolismo , Extractos Vegetales/metabolismo , Plantas Medicinales/química , Receptor X de Pregnano , Ratas , Receptores de Esteroides/metabolismo , Tanzanía
18.
BMC Oral Health ; 6: 12, 2006 Aug 18.
Artículo en Inglés | MEDLINE | ID: mdl-16916469

RESUMEN

BACKGROUND: The aim of the study was to compare the prevalence and types of HIV-related oral lesions between children and adult Tanzanian patients on HAART with those not on HAART and to relate the occurrence of the lesions with anti-HIV drug regimen, clinical stage of HIV disease and CD4+ cell count. METHODS: Participants were 532 HIV infected patients, 51 children and 481 adults, 165 males and 367 females. Children were aged 2-17 years and adults 18 and 67 years. Participants were recruited consecutively at the Muhimbili National Hospital (MNH) HIV clinic from October 2004 to September 2005. Investigations included; interviews, physical examinations, HIV testing and enumeration of CD4+ T cells. RESULTS: A total of 237 HIV-associated oral lesions were observed in 210 (39.5%) patients. Oral candidiasis was the commonest (23.5%), followed by mucosal hyperpigmentation (4.7%). There was a significant difference in the occurrence of oral candidiasis (chi2 = 4.31; df = 1; p = 0.03) and parotid enlargement (chi2 = 36.5; df = 1; p = 0.04) between children and adults. Adult patients who were on HAART had a significantly lower risk of; oral lesions (OR = 0.32; 95% CI = 0.22-0.47; p = 0.005), oral candidiasis (OR = 0.28; 95% CI = 0.18-0.44; p = 0.003) and oral hairy leukoplakia (OR = 0.18; 95% CI = 0.04-0.85; p = 0.03). There was no significant reduction in occurrence of oral lesions in children on HAART (OR = 0.35; 95% CI = 0.11-1.14; p = 0.15). There was also a significant association between the presence of oral lesions and CD4+ cell count < 200 cell/mm3 (chi2 = 52.4; df = 2; p = 0.006) and with WHO clinical stage (chi2 = 121; df = 3; p = 0.008). Oral lesions were also associated with tobacco smoking (chi2 = 8.17; df = 2; p = 0.04). CONCLUSION: Adult patients receiving HAART had a significantly lower prevalence of oral lesions, particularly oral candidiasis and oral hairy leukoplakia. There was no significant change in occurrence of oral lesions in children receiving HAART. The occurrence of oral lesions, in both HAART and non-HAART patients, correlated with WHO clinical staging and CD4+ less than 200 cells/mm3.

19.
J Ethnopharmacol ; 108(1): 124-32, 2006 Nov 03.
Artículo en Inglés | MEDLINE | ID: mdl-16829001

RESUMEN

Using the ethnobotanical approach, some Tanzanian plants reported to be used by traditional healers for the treatment of oral candidiasis and fungal infections of the skin were collected and screened for their antifungal activity against Candida albicans, Candida glabrata, Candida tropicalis, Candida parapsilosis, Candida krusei and Cryptococcus neoformans. A total of 65 crude methanol extracts belonging to 56 plant species and 38 families were screened using the broth microdilution method, according to the guidelines of the Clinical and Laboratory Standard Institute (CLSI) (formerly, National Committee for Clinical and Laboratory Standards) [National Committee for Clinical Laboratory Standards, 2002. Reference Method for Broth Dilution Antifungal Susceptibility Testing of Yeasts. Approved Standard-2nd Edition M27-A2, National Committee for Clinical Laboratory Standards, Wayne, PA, USA]. Among the tested plant species, 45% (25 species) showed antifungal activity against one or more of the test fungi. The most susceptible yeasts were Cryptococcus neoformans, followed by Candida krusei, Candida tropicalis, and Candida parapsilosis. The least susceptible were Candida albicans and Candida glabrata. Strong antifungal activity was exhibited by extracts of Clausena anisata Oliv., Sclerocariya birrea Sond, Turraea holstii Gurk, Sterculia africana (Lour) Fiori, Acacia robusta subsp. Usambarensis (Taub) Brenan, Cyphosterma hildebrandti (Gilg), Desc, Elaeodendron buchannanii (Lows), Acacia nilotica (L.) Wild ex Del, Jatropha multifida L., and Pteridium aquilinum (L.) Kuhn.


Asunto(s)
Antifúngicos/química , Antifúngicos/farmacología , Hongos/efectos de los fármacos , Medicinas Tradicionales Africanas , Preparaciones de Plantas/química , Preparaciones de Plantas/farmacología , Plantas Medicinales/química , Etnofarmacología , Pruebas de Sensibilidad Microbiana , Tanzanía
20.
Afr J Tradit Complement Altern Med ; 4(2): 219-25, 2006 Nov 13.
Artículo en Inglés | MEDLINE | ID: mdl-20162095

RESUMEN

Plants which are used by traditional healers in Tanzania have been evaluated to obtain preliminary data of their toxicity using the brine shrimps test. The results indicate that 9 out of 44 plant species whose extracts were tested exhibited high toxicity with LC(50) values below 20 microg/ml. These include Aloe lateritia Engl. (Aloaceae) [19.1 microg/ml], Cassia abbreviata Oliv. (Caesalpiniaceae) [12.7 microg/ml], Croton scheffleri Pax (Euphorbiaceae) [13.7 microg/ml], Hymenodactyon parvifolium Brig (Rubiaceae) [13.4 microg/ml], Kigelia Africana L. (Bignoniaceae) [7.2 microg/ml], and Ocimum suave Oliv. (Labiatae) [16.7 microg/ml]. Twelve plants gave LC(50) values between 21 and 50 microg/ml, 11 plants gave LC(50) values between 50 and 100 microg/ml, and 18 plants gave LC(50) values greater than 100 microg/ml.

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