Ten Years Follow Up of Patients with Tinnitus and Normal Hearing.

OBJECTIVE: To describe the natural history of tinnitus in normal hearing patients. STUDY DESIGN: This is a prospective longitudinal observational study. SETTING: Tertiary University Hospital. METHODS: In 2009 we studied 68 patients with significant tinnitus and normal hearing (Study Group-SG) compared to 46 patients with normal hearing and no tinnitus (Control Group-CG). We have been able to contact and recruit 24 patients from SG (35.3 %) and ten patients from CG) (21.74%) in 2019. Both groups were submitted to conventional audiometry, Distortion Product Otoacoustic Emissions (DPOAE), Tinnitus Handicap Inventory (THI), Visual Analog Scale (VAS) and Beck`S Depression and Anxiety Scales (BDS, BAS). These measures were compared with the same ones performed ten years ago in the same groups of patients. The software SPSS for windows version 21 was used. P values <0.05 were considered significant. Student t test was used to compare SG and CG results in 2019 and to compare 2009 and 2019 outcomes.. RESULTS: Hearing loss, especially in the higher frequencies, were significantly worse in SG compared to GC in 2019. DPOAE were significantly worse in SG and CG in 2019 however CG had more abnormal results than SG. These results suggest that outer hair cells lesions are not the only determinant for tinnitus and hearing loss development. CONCLUSIONS: These results suggest that outer hair cells lesions are not the only determinant for tinnitus and hearing loss development.

The promising drugs included in WHO's Solidarity Project: a choice based in scientific knowledge and institutional competencies.

BACKGROUND: In March 2020, the World Health Organization (WHO) launched the Solidarity Program, probably the largest global initiative to encourage and support research in four promising drugs, named Remdesivir, Hydroxychloroquine, ß Interferon and the combination Lopinavir / Ritonavir, to reduce the mortality of Coronavirus disease 2019 (COVID-19). OBJECTIVES: Considering the potential impact of Solidarity Program to restrain the current pandemic, the present study aims to investigate whether it was designed upon indicators of scientific productivity, defined as the level of the production of new scientific knowledge and of the institutional capabilities, estimated in terms of scientific publications and technological agreements. METHODS: The scientific documents on Alphacoronavirus, Betacoronavirus, Gammacoronavirus and Coronavirus were retrieved from Scopus database while the technological agreements on coronavirus were obtained through Cortellis. As for the institutions and countries, we have considered the data on author's affiliations in both set of data. For comparison, we included the analysis of documents related with other drugs or therapies, such as vaccines and antibodies, which were listed in a Clarivate's report on coronaviruses research. FINDINGS: Most of the analysis refers to documents on Coronavirus, the largest group. The number of documents related to WHO's drugs are almost five times higher than in the other groups. This subset of documents involves the largest and most diverse number of institutions and countries. As for agreements, we observed a smaller number of institutions involved in it, suggesting differences between countries in terms of technical and human capabilities to develop basic and/or clinical research on coronavirus and to develop new forms or products to treat or to prevent the disease. MAIN CONCLUSIONS: Hence, the results shown in this study illustrate that decisions taken by an international scientific body, as WHO, were mainly based in scientific knowledge and institutional competencies.

Expression, purification, and characterization of asparaginase II from Saccharomyces cerevisiae in Escherichia coli.

l-asparaginase catalyzes the conversion of l-asparagine to l-aspartate and ammonium. This protein is an important therapeutic enzyme used for the treatment of acute lymphoblastic leukemia. In this study, the asparaginase II-encoding gene ASP3 from Saccharomyces cerevisiae was cloned into the expression vector pET28a in-fusion with a 6x histidine tag and was expressed in Escherichia coli BL21 (DE3) cells. The protein was expressed at a high level (225.6 IU/g cells) as an intracellular and soluble molecule and was purified from the supernatant by nickel affinity chromatography. The enzyme showed very low activity against l-glutamine. The denaturing electrophoresis analysis indicated that the recombinant protein had a molecular mass of ∼38 kDa. The native enzyme was a tetramer with a molecular mass of approximately 178 kDa. The enzyme preparation showed antitumor activity against the K562 and Jurkat cell lines comparable or even superior to the E. coli commercial asparaginase.

Effects of septorhinoplasty on smell perception.

PURPOSE: To assess whether significant changes in smell perception occur after septorhinoplasty, and evaluate whether septum deviation, allergic rhinitis, and surgical technique affect postoperative smell perception. METHODS: Thirty-four patients (> 18 years old) awaiting septorhinoplasty were included, while those with previous severe hyposmia or anosmia were excluded. The participants self-assessed their smell perception using a 100-mm visual analogue scale (VAS), where 0 mm indicated the inability to smell and 100 mm indicated normal smell perception. The University of Pennsylvania Smell Identification Test (UPSIT) was applied before the procedure, and 4 and 12 weeks after surgery. RESULTS: The UPSIT score showed no significant changes at 4 (p = 0.59; 95% CI - 0.35 to + 2) or 12 weeks (p = 0.16; 95% CI - 1.13 to + 0.66). A comparison of the VAS scores before and 4 weeks after surgery (p = 0.62; 95% CI - 0.63 to + 0.39) yielded similar results. However, the average VAS scores improved 12 weeks after surgery (p = 0.007; 95% CI + 0.22 to + 1.30). Olfactory function, measured using the UPSIT, was not influenced by open or closed surgical techniques (p ≥ 0.10), the presence or absence of rhinitis (p ≥ 0.15), or obstructive septum deviation (p ≥ 0.38). Twelve weeks after surgery, self-evaluated smell perception was better in patients who underwent a closed procedure rather than an open procedure (p = 0.006; 95% CI: -1.39 to -0.37). CONCLUSION: A validated test demonstrates that septorhinoplasty does not compromise smell perception 4 and 12 weeks after surgery. However, it might improve smell perception by the self-report observation.

Prenatal sonographic diagnosis of isolated fetal ascites in cri-du-chat (5p-) syndrome: A case report.

Isolated fetal ascites and cri-du-chat syndrome (CdCS; OMIM #123450) are two very rare conditions that, to our best knowledge, have never been reported together. Here, we describe a case of isolated fetal ascites detected in the first trimester ultrasound, with no other remarkable signs. After an extensive work-up (fetal ultrasound, serologies, Coombs test, and NIPT), an amniocentesis was performed and revealed an abnormal karyotype of 46,XX,del(5)(p15.2), characteristic of CdCS. We hypothesize that isolated fetal ascites has to be considered an antenatal ultrasonographic marker for CdCS, a finding that should be confirmed in further cases.

Prevalence of metabolic syndrome in rheumatoid arthritis patients from Northeastern Brazil: Association with disease activity.

OBJECTIVES: To determine the prevalence of metabolic syndrome (MetS) in patients with rheumatoid arthritis (RA) and controls from Northeastern Brazil and to verify its association with specific RA parameters and cardiovascular risk factors. METHODS: The prevalence of MetS was assessed cross-sectionally in 338 RA patients from a single center and 84 age and gender-matched controls from the local community. MetS was defined according to NCEP/ATPIII guidelines. Disease activity was assessed with CDAI, SDAI and DAS28 scores. Independent risk factors for MetS in RA patients were identified by multivariate logistic regression. RESULTS: The prevalence of MetS was higher in RA patients than in controls (51.3% vs. 21.8%; p < .001). RA patients had a higher frequency of hypertension and type-2 diabetes mellitus, greater waist circumference (WC), higher blood glucose levels and lower HDL levels. DAS28, CDAI and SDAI scores were higher and high disease activity was more frequent in MetS patients. The multivariate logistic regression identified BMI (OR = 1.12, 95% CI = 1.05-1.20; p < .001) and disease activity (OR = 1.23, 95% CI = 1.04-1.47; p = .016) as independent risk factors for MetS in patients with RA. CONCLUSION: RA in patients from Northeastern Brazil was found to be associated with increased WC, high prevalence of MetS (one of the highest in the world) and disease activity. Patients with MetS displayed a higher frequency of cardiovascular risk factors, indicating the need for better control of disease activity and modifiable risk factors for cardiovascular disease (CVD).

Analysis of Hearing and Tinnitus in Workers Exposed to Occupational Noise.

INTRODUCTION: Noise is one of the harmful agents to health that is present in the various branches of economic activity. Hearing loss and tinnitus are among the most frequently reported complaints by workers exposed to occupational noise. OBJECTIVE: To analyze the hearing and tinnitus in normal-hearing workers exposed to occupational noise. METHODS: This is a cross-sectional analytical trial in metallurgical industries, in which we evaluated normal-hearing workers through anamnesis, audiometry and otoacoustic emissions. RESULTS: It was observed high prevalence of failure of otoacoustic emissions (40%) and tinnitus (66.6%). Both in the amplitude and in the signal-to-noise ratio, the higher is the frequency of the sound, the worse the results. Despite having audiometry within normal limits, the results indicate that workers are suffering the effects of exposure and reveals association between failure of otoacoustic emissions and tinnitus in this population (X2 = 6,732). CONCLUSION: It is concluded that failures in DPOAE and tinnitus are predictors of hearing damage in normal-hearing workers.

Saccharomyces cerevisiae asparaginase II, a potential antileukemic drug: Purification and characterization of the enzyme expressed in Pichia pastoris.

Asparaginase obtained from Escherichia coli and Erwinia chrysanthemi are used to treat acute lymphocytic leukaemia and non-Hodgkin's lymphoma. However, these agents cause severe adverse effects. Saccharomyces cerevisiae asparaginase II, encoded by the ASP3 gene, could be a potential candidate for the formulation of new drugs. This work aimed to purify and characterize the periplasmic asparaginase produced by a recombinant Pichia pastoris strain harbouring the ASP3 gene. The enzyme was purified to homogeneity with an activity recovery of 51.3%. The estimated molecular mass of the enzyme was 136 kDa (under native conditions) and 48.6 kDa and 44.6 kDa (under reducing conditions), suggesting an oligomeric structure. The recombinant asparaginase is apparently non-phosphorylated, and the major difference between the monomers seems to be their degree of glycosylation. The enzyme showed an isoelectric point of 4.5 and maximum activity at 46 °C and pH 7.2, retaining 92% of the activity at 37 °C. Circular dichroism and fluorescence analyses showed that the enzyme structure is predominantly α-helical with the contribution of ß-sheet and that it remains stable up to 45 °C and in the pH range of 6-10. In vitro tests indicated that the recombinant asparaginase demonstrated antitumoural activity against K562 leukaemic cells.

Tinnitus Annoyance in Normal-Hearing Individuals: Correlation With Depression and Anxiety.

OBJECTIVE: To assess and correlate tinnitus annoyance in normal-hearing patients with auditory brainstem response and with anxiety/depression. METHODS: A sample of 84 individuals with tinnitus and normal hearing levels (pure-tone thresholds ≤25 dB HL) was compared to a matched control group of 47 normal-hearing individuals without tinnitus. All participants underwent auditory brainstem response testing. Tinnitus annoyance was assessed using the Tinnitus Handicap Inventory and depression and anxiety using the Beck Depression Inventory and Beck Anxiety Inventory, respectively. We compared auditory brainstem response and anxiety/depression symptoms between groups. In the study group, we correlated the degree of tinnitus annoyance with normal/abnormal auditory brainstem response and presence/level of anxiety/depression symptoms. RESULTS: All controls had normal auditory brainstem response; 30 patients with tinnitus had abnormal results. Thirty-five patients with tinnitus had depression and 41 anxiety, while only 2 controls had depression and none had anxiety, with a significant between-group difference (P < .001). Normal/abnormal auditory brainstem response showed no association with tinnitus annoyance, anxiety, or depression. A higher degree of tinnitus annoyance was associated with severity of depression and anxiety. CONCLUSIONS: Increased tinnitus annoyance was positively correlated with greater severity of anxiety and depression in normal-hearing patients but was unrelated to normal/abnormal auditory brainstem response.

Risk of hearing alterations in newborns of mothers treated for malaria.

INTRODUCTION: The antimalarial drugs can cause irreversible sensorineural hearing loss, and chloroquine phosphate use can be ototoxic to the fetus. OBJECTIVE: To compare the results of hearing screening in newborns of mothers treated for malaria in pregnancy with the results of newborns of mothers untreated and check for increased risk of hearing alterations in the group exposed to treatment. METHOD: Retrospective cohort study which involved 284 infants, 30 in the exposed group to malaria treatment and 254 in the unexposed group, matched for gestational age, birth weight and risk indicators for hearing. They underwent hearing screening by means of transient evoked otoacoustic emissions and/or auditory brainstem response automatic. The variables were collected in an interview with the parents in the health record and the screening database. RESULTS: The prevalence of fail in exposed group (6.7%) was significant when compared with the unexposed group (1.2%). The risk of failing in the hearing screening in the exposed group was 5.64 (CI 1.17 to 27.3). CONCLUSION: Newborns of mothers treated for malaria in pregnancy had a prevalence of fail in hearing screening at 6.7% and 5.64 higher chances to fail than newborns of untreated mothers.

The chemopreventive effect of Ginkgo biloba extract 761 against cisplatin ototoxicity: a pilot study.

OBJECTIVE: The purpose of this study was to evaluate, by using distortion product otoacoustic emission test, the action of Ginkgo biloba extract 761, which has a known antioxidant property, as a possible otoprotective against cisplatin induced hearing loss. This prospective and double blinded study was conducted on individuals that were to begin cisplatin treatment in a tertiary university center. They were randomized and allocated in two groups: control group (CG) (n = 07) receiving placebo and cisplatin and study group (SG) (n = 08) receiving Ginkgo biloba extract 761 (240 mg/day) and cisplatin. METHODS: This prospective study was conducted on individuals that were treated by cancer with cisplatin (CDDP) in a tertiary University center. Both groups were instructed to ingest the either placebo or Ginkgo biloba extract 761 before the first cisplatin dose. They were rated and followed up for approximately 90 days. The maximum cumulative cisplatin dosage was 300 mg/m(2). The ototoxic effect was measured with distortion product otoacoustic emissions. Distortion product otoacoustic emissions were recorded before the first cisplatin cycle, 30, 60 and 90 days after the treatment. The average of the amplitude of the signals were calculated and used for comparisons between the groups. RESULTS: Comparisons were made between baseline measurements and those recorded after maximum cumulative CDDP dose. The control group showed smaller distortion product otoacoustic emissions mean amplitudes and smaller signal/noise ratio than the study group (p < 0.05). CONCLUSION: Ginkgo biloba extract 761 probably has antioxidant properties, and might play otoprotective effect against cisplatin ototoxicity in these patients.

Association between suppression of otoacoustic emissions and annoyance levels in tinnitus patients with normal hearing.

OBJECTIVE: To correlate the annoyance of tinnitus assessed by the Tinnitus Handicap Inventory and on a visual analogue scale with the evoked otoacoustic emission test result in tinnitus patients with normal hearing. STUDY DESIGN: Case-control study. SETTING: Public tertiary hospital. SUBJECTS AND METHODS: The sample was initially based on a population of 80 subjects with tinnitus; 20 of them had normal hearing and normal evoked otoacoustic emission test results and comprised the study group. For the purpose of comparison, a control group was formed, which consisted of 17 subjects with no hearing complaints and normal hearing. The participants were submitted to hearing tests, immittance testing and tests for the evaluation of acoustic reflexes, distortion product otoacoustic emissions, transient evoked otoacoustic emissions (TEOAEs), and suppression of TEOAEs. The tests were performed in a sound-treated booth using a linear contralateral noise of 60 dB. The presence of suppression effects was defined when the response amplitude was 0.5 dB or higher. RESULTS: Abnormal evoked otoacoustic emission suppression test results were observed in 52.9% of tinnitus patients and in 32.4% of control subjects (p = 0.086). Suppression effects of TEOAEs were absent in 38.5% of subjects with minimal or mild discomfort and in 61.9% of subjects with moderate or severe discomfort (p = 0.183). CONCLUSION: It was not possible to associate the annoyance caused by tinnitus with the TEOAE suppression test results, although suppression effects were found to decrease with increasing annoyance.

Prevalence of hearing loss in newborns of mothers who had malaria and were treated with antimalaric drugs in pregnancy.

INTRODUCTION: Gestational malaria is related to very bad perinatal outcomes and antimalarial drugs used during pregnancy can be ototoxic to the fetus. OBJECTIVE: To determine the prevalence of hearing loss in newborns of mothers who had malaria and treated with antimalarial drugs during pregnancy. MATERIALS AND METHODS: Cross-sectional study which involved 35 newborns. All underwent neonatal hearing screening with otoacoustic emissions combined with automatic auditory brainstem response. Those who failed were referred to audiological diagnosis with evoked otoacoustic emissions and brainstem auditory evoked potential associated with tympanometry (1000 Hz). Data were obtained through interviews with the mothers' and analyzing the patient chart and the newborn, and underwent to statistical tests analysis of variance, equality of two proportions and Chi-square test (p = 0.05). RESULTS: The infection by Plasmodium vivax and chloroquine treatment with the first quarter prevailed; 88.6% (n = 31) newborns passed the hearing screening and 11.4% (n = 4) failed, of these, 50% (n = 2) attended for diagnosis, being diagnosed with hearing loss. CONCLUSION: The prevalence of hearing loss in newborns of mothers who had vivax malaria and used chloroquine during pregnancy was 3%.

A Novel Trypsin Kunitz-Type Inhibitor from Cajanus cajan Leaves and Its Inhibitory Activity on New Cancer Serine Proteases and Its Effect on Tumor Cell Growth.

A novel trypsin inhibitor from Cajanus cajan (TIC) fresh leaves was partially purified by affinity chromatography. SDS-PAGE revealed one band with about 15 kDa with expressive trypsin inhibitor activity by zymography. TIC showed high affinity for trypsin (Ki = 1.617 µM) and was a competitive inhibitor for this serine protease. TIC activity was maintained after 24 h of treatment at 70 °C, after 1 h treatments with different pH values, and ß-mercaptoethanol increasing concentrations, and demonstrated expressive structural stability. However, the activity of TIC was affected in the presence of oxidizing agents. In order to study the effect of TIC on secreted serine proteases, as well as on the cell culture growth curve, SK-MEL-28 metastatic human melanoma cell line and CaCo-2 colon adenocarcinoma was grown in supplemented DMEM, and the extracellular fractions were submitted salting out and affinity chromatography to obtain new secreted serine proteases. TIC inhibited almost completely, 96 to 89%, the activity of these serine proteases and reduced the melanoma and colon adenocarcinoma cells growth of 48 and 77% respectively. Besides, it is the first time that a trypsin inhibitor was isolated and characterized from C. cajan leaves and cancer serine proteases were isolated and partial characterized from SK-MEL-28 and CaCo-2 cancer cell lines. Furthermore, TIC shown to be potent inhibitor of tumor protease affecting cell growth, and can be one potential drug candidate to be employed in chemotherapy of melanoma and colon adenocarcinoma.

Task force of the Brazilian Society of Otology - evaluation and management of peripheral facial palsy.

OBJECTIVE: To review key evidence-based recommendations for the diagnosis and treatment of peripheral facial palsy in children and adults. METHODS: Task force members were educated on knowledge synthesis methods, including electronic database search, review and selection of relevant citations, and critical appraisal of selected studies. Articles written in English or Portuguese on peripheral facial palsy were eligible for inclusion. The American College of Physicians' guideline grading system and the American Thyroid Association's guideline criteria were used for critical appraisal of evidence and recommendations for therapeutic interventions. RESULTS: The topics were divided into 2 main parts: (1) Evaluation and diagnosis of facial palsy: electrophysiologic tests, idiopathic facial palsy, Ramsay Hunt syndrome, traumatic peripheral facial palsy, recurrent peripheral facial palsy, facial nerve tumors, and peripheral facial palsy in children; and (2) Rehabilitation procedures: surgical decompression of the facial nerve, facial nerve grafting, surgical treatment of long-term peripheral facial palsy, and non-surgical rehabilitation of the facial nerve. CONCLUSIONS: Peripheral facial palsy is a condition of diverse etiology. Treatment should be individualized according to the cause of facial nerve dysfunction, but the literature presents better evidence-based recommendations for systemic corticosteroid therapy.

Biphasic modulation of NOS expression, protein and nitrite products by hydroxocobalamin underlies its protective effect in endotoxemic shock: downstream regulation of COX-2, IL-1ß, TNF-α, IL-6, and HMGB1 expression.

BACKGROUND: NOS/•NO inhibitors are potential therapeutics for sepsis, yet they increase clinical mortality. However, there has been no in vivo investigation of the (in vitro) •NO scavenger, cobalamin's (Cbl) endogenous effects on NOS/•NO/inflammatory mediators during the immune response to sepsis. METHODS: We used quantitative polymerase chain reaction (qPCR), ELISA, Western blot, and NOS Griess assays, in a C57BL/6 mouse, acute endotoxaemia model. RESULTS: During the immune response, pro-inflammatory phase, parenteral hydroxocobalamin (HOCbl) treatment partially inhibits hepatic, but not lung, iNOS mRNA and promotes lung eNOS mRNA, but attenuates the LPS hepatic rise in eNOS mRNA, whilst paradoxically promoting high iNOS/eNOS protein translation, but relatively moderate •NO production. HOCbl/NOS/•NO regulation is reciprocally associated with lower 4 h expression of TNF-α, IL-1ß, COX-2, and lower circulating TNF-α, but not IL-6. In resolution, 24 h after LPS, HOCbl completely abrogates a major late mediator of sepsis mortality, high mobility group box 1 (HMGB1) mRNA, inhibits iNOS mRNA, and attenuates LPS-induced hepatic inhibition of eNOS mRNA, whilst showing increased, but still moderate, NOS activity, relative to LPS only. experiments (LPS+D-Galactosamine) HOCbl afforded significant, dose-dependent protection in mice. CONCLUSIONS: HOCbl produces a complex, time- and organ-dependent, selective regulation of NOS/•NO during endotoxaemia, corollary regulation of downstream inflammatory mediators, and increased survival. This merits clinical evaluation.

Stapedotomy in a residency training program.

INTRODUCTION: The major objective of a stapedotomy is the restoration of hearing. In training centers, the hearing results obtained by resident physicians are lower than those achieved by more experienced surgeons. An analysis of the surgical results obtained by resident physicians is essential to identification of the deficiencies in the learning process. OBJECTIVE: To analyze the postoperative hearing results obtained by otosclerosis patients who underwent stapedotomy performed by surgeons in a residency program. METHODS: The pre- and postoperative audiometric results were evaluated in a retrospective study of 98 otosclerosis patients who underwent stapedotomy from January 2000 to December 2010. RESULTS: The distribution of patients according to the postoperative results was as follows: 68.4% of the patients achieved a postoperative gap of less than or equal to 10 dB, and 91.8% of the patients achieved a postoperative gap of less than or equal to 20 dB. Three (3.1%) patients had profound sensorineural hearing loss after the procedure. CONCLUSIONS: An improvement in surgical outcomes of doctors in training is essential for the continuation of training for stapes surgery during medical residency.

Effect of hormone replacement therapy on the auditory brainstem response of postmenopausal women.

OBJECTIVE: To investigate whether hormone replacement therapy modifies the auditory brainstem response in postmenopausal women. METHODS: Nineteen postmenopausal women received hormone replacement therapy (study group) and 25 received no treatment nor placebo (control group). In both groups, age ranged from 45 to 60 years and pure-tone sensitivity was 25 dB or better at frequencies between 500 and 2000 Hz. Auditory brainstem response was evaluated before and after 3 months of hormone use in the study group. The control group was also evaluated at the same periods. The following auditory brainstem response parameters were compared between the two groups: latencies of waves I, III, and V; I-III, III-V, and I-V interpeak intervals. RESULTS: Mean age did not differ between groups (study group: 51.5 ± 0.7 years; control: 52.9 ± 0.6 years). No significant differences in wave latencies, or interpeak intervals were observed between the two groups (p > 0.05).

Changes in the communicative skills of young people as a result of a communication training.

PURPOSE: To analyze the effect of communication training developed for adolescents on the youth's communication skills. METHODS: Forty-one young people participated in the study and were divided into two groups. Group I received intervention - communication training for five weeks; Group II - were guided on the importance of voice for communication. Participants had their communication skills assessed before/after interventions through a self-administered questionnaire, answered by the participant and parents. Both groups had oral presentations recorded on video, which were analyzed by speech therapists through the evaluation of the communication profile, listing the aspects that should be observed as a point of strength/opportunity for improvement. Association between qualitative variables was assessed using Fischer's exact test, Pearson's chi-square test, McNemar's test, and McNemar-Bowker's test. To compare groups, paired t-test and t-test for independent samples, p level <0.05, were used. RESULTS: The analysis of questionnaires showed improvement in GI in two of the four skills assessed and no difference for GII. The video evaluations showed a significant difference between the groups in terms of eye contact and speech velocity. CONCLUSION: This study points out that the communication training method applied to young people might improve communicative skills, providing some insights into their communication strengths and potential areas for development.

Aurelianolides from Aureliana fasciculata var. fasciculata Trigger Apoptosis With Caspase Activation in Human Leukemia Cells.

BACKGROUND/AIM: Aurelianolide A and B were identified and isolated from Aureliana fasciculata var. fasciculata leaves. Withanolides are naturally occurring C-28 steroidal lactone triterpenoids with cytotoxic and anticancer properties, among other relevant pharmacological activities. Herein we have described, for the first time, the cytotoxic effects of aurelianolides on human cancer cells. MATERIALS AND METHODS: Aurelianolide A and B were tested on human leukemia cell lines: THP-1, MOLT-4, Jurkat, K562 and K562-Lucena 1. RESULTS: For aurelianolide A, MOLT-4 had the lower IC50 (1.17 µM) and for aurelianolide B, Jurkat was the most susceptible cell line (IC50 2.25 µM). On the other hand, the multidrug resistant (MDR) cell line K562-Lucena 1 showed higher IC50 for both aurelianolides. Using 293T, a non-tumor embryonic kidney cell line, we observed an excellent selectivity index for both aurelianolides, from 2.24 (aurelianolide B in K562-Lucena 1) to 45.5 (aurelianolide A in MOLT-4). Aurelianolide A and B activated caspase 3/7 with consequent induction of apoptosis on Jurkat and K562-Lucena 1 cell lines. We have not observed induction of necrosis. CONCLUSION: Aurelianolides A and B have important cytotoxic effects on human leukemia cell lines by the activation of the caspase pathway.