Borohydride Compounds Catalyze the Selective 4e- Reduction of CO2 with 9-BBN.

The selective double hydroboration of CO2 into bis(boryl)acetal (BBA) is a challenging yet appealing reduction process since BBA can be used as a versatile C1 and Cn sources for the synthesis of value-added products. In the present study, we demonstrate that simple borohydride compounds are efficient and selective catalysts for the synthesis of BBA when using 9-borabicyclo(3.3.1)nonane (9-BBN) as a reductant. The experimental and theoretical investigations show that while the borohydride species catalyzes the first reduction step of CO2 into formoxyborane (2e- reduction intermediate), the observed 4e- reduction selectivity is mostly due to the ability of 9-BBN to reduce the formoxyborane into BBA without a catalyst. Notably, 0.2 mol % of LiH2BBN catalyzed the hydroboration of CO2 with 9-BBN as a reductant into the corresponding BBA in 77% yield with TON and TOF of 385 and 196 h-1, respectively. The simplicity of borohydride contrasts with the more elaborate catalytic systems used so far for the 4e- reduction of CO2.

Adherence to Treatment Guidelines in Ambulatory Heart Failure Patients with Reduced Ejection Fraction in a Latin-American Country: Observational Study of the Colombian Heart Failure Registry (RECOLFACA).

INTRODUCTION: Although several guidelines recommend that patients with heart failure with reduced ejection fraction (HFrEF) be treated with angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers (ACEIs/ARBs) or angiotensin receptor-neprilysin inhibitors (ARNIs), beta-blockers, mineralocorticoid receptor antagonists (MRAs), and sodium-glucose cotransporter-2 inhibitor (SGLT2i), there are still several gaps in their prescription and dosage in Colombia. This study aimed to describe the use patterns of HFrEF treatments in the Colombian Heart Failure Registry (RECOLFACA). METHODS: Patients with HFrEF enrolled in RECOLFACA during 2017-2019 were included. Heart failure (HF) medication prescription and daily dose were assessed using absolute numbers and proportions. Therapeutic schemes of patients treated by internal medicine specialists were compared with those treated by cardiologists. RESULTS: Out of 2,528 patients in the registry, 1,384 (54.7%) had HFrEF. Among those individuals, 88.9% were prescribed beta-blockers, 72.3% with ACEI/ARBs, 67.9% with MRAs, and 13.1% with ARNIs. Moreover, less than a third of the total patients reached the target doses recommended by the European HF guidelines. No significant differences in the therapeutic schemes or target doses were observed between patients treated by internal medicine specialists or cardiologists. CONCLUSION: Prescription rates and target dose achievement are suboptimal in Colombia. Nevertheless, RECOLFACA had one of the highest prescription rates of beta-blockers and MRAs compared to some of the most recent HF registries. However, ARNIs remain underprescribed. Continuous registry updates can improve the identification of patients suitable for ARNI and SGLT2i therapy to promote their use in clinical practice.

Electrophysiological Measures of Listening-in-Noise With and Without Remote Microphone System Use in Autistic and Non-Autistic Youth.

OBJECTIVES: This study examined the neural mechanisms by which remote microphone (RM) systems might lead to improved behavioral performance on listening-in-noise tasks in autistic and non-autistic youth. DESIGN: Cortical auditory evoked potentials (CAEPs) were recorded in autistic (n = 25) and non-autistic (n = 22) youth who were matched at the group level on chronological age ( M = 14.21 ± 3.39 years) and biological sex. Potentials were recorded during an active syllable identification task completed in quiet and in multi-talker babble noise with and without the use of an RM system. The effects of noise and RM system use on speech-sound-evoked P1-N1-P2 responses and the associations between the cortical responses and behavioral performance on syllable identification were examined. RESULTS: No group differences were observed for behavioral or CAEP measures of speech processing in quiet or in noise. In the combined sample, syllable identification in noise was less accurate and slower than in the quiet condition. The addition of the RM system to the noise condition restored accuracy, but not the response speed, to the levels observed in quiet. The CAEP analyses noted amplitude reductions and latency delays in the noise compared with the quiet condition. The RM system use increased the N1 amplitude as well as reduced and delayed the P2 response relative to the quiet and noise conditions. Exploratory brain-behavior correlations revealed that larger N1 amplitudes in the RM condition were associated with greater behavioral accuracy of syllable identification. Reduced N1 amplitude and accelerated P2 response were associated with shorter syllable identification response times when listening with the RM system. CONCLUSIONS: Findings suggest that although listening-in-noise with an RM system might remain effortful, the improved signal to noise ratio facilitates attention to the sensory features of the stimuli and increases speech sound identification accuracy.

Health insurance and clinical outcomes in patients with chronic heart failure in Latin America: an observational study of the Colombian Heart Failure Registry (RECOLFACA).

The effect of the health insurance type on the prognosis of heart failure (HF) patients in Colombia and Latin America is poorly known. We aimed to analyze the characteristics of HF patients that participated in the Colombian Heart Failure Registry (RECOLFACA) as stated by their health insurance type and their relationship with the immediate prognosis of these patients. Patients with HF diagnosis were included in the RECOLFACA registry between 2017-2019. The registry was conducted in 60 centers in Colombia. All-cause mortality was the principal outcome. To evaluate the impact of health insurance on mortality, a Cox proportional hazards regression model was used. The Kaplan-Meier analysis was performed to compare survival probabilities according to insurance type. All statistical analyses were two-tailed and were considered significant with a p value < 0.05. Of the 2,528 participants enrolled in the registry, 99% held details about their health insurance. Of those, 897 patients (35.6%) were covered by public insurance. These patients were significantly younger, with a lower proportion of men, more frequently from rural origin, and lower prevalence of most comorbidities (omitting hypertension, chronic obstructive pulmonary disease (COPD), and Chagas disease) than those with private insurance. Furthermore, patients with public insurance had a worse functional class, as well as a poorer quality of life, and lower frequency of use of implantable devices, while exhibiting similar prescription rates of triple medical therapy for HF. Finally, no differences in short-term mortality were observed between the two groups (HR 1.09; 95% CI 0.79, 1.51). The type of health insurance represents a condition related with relevant differences in the profile of patients with HF in Colombia. Despite this, no significant differences were detected in the short-term prognosis of these patients based on the type of health insurance.

Plasticity Changes in Central Auditory Systems of School-Age Children Following a Brief Training With a Remote Microphone System.

OBJECTIVES: The objective of this study was to investigate whether a brief speech-in-noise training with a remote microphone (RM) system (favorable listening condition) would contribute to enhanced post-training plasticity changes in the auditory system of school-age children. DESIGN: Before training, event-related potentials (ERPs) were recorded from 49 typically developing children, who actively identified two syllables in quiet and in noise (+5 dB signal-to-noise ratio [SNR]). During training, children completed the same syllable identification task as in the pre-training noise condition, but received feedback on their performance. Following random assignment, half of the sample used an RM system during training (experimental group), while the other half did not (control group). That is, during training' children in the experimental group listened to a more favorable speech signal (+15 dB SNR) than children from the control group (+5 dB SNR). ERPs were collected after training at +5 dB SNR to evaluate the effects of training with and without the RM system. Electrical neuroimaging analyses quantified the effects of training in each group on ERP global field power (GFP) and topography, indexing response strength and network changes, respectively. Behavioral speech-perception-in-noise skills of children were also evaluated and compared before and after training. We hypothesized that training with the RM system (experimental group) would lead to greater enhancement of GFP and greater topographical changes post-training than training without the RM system (control group). We also expected greater behavioral improvement on the speech-perception-in-noise task when training with than without the RM system. RESULTS: GFP was enhanced after training only in the experimental group. These effects were observed on early time-windows corresponding to traditional P1-N1 (100 to 200 msec) and P2-N2 (200 to 400 msec) ERP components. No training effects were observed on response topography. Finally, both groups increased their speech-perception-in-noise skills post-training. CONCLUSIONS: Enhanced GFP after training with the RM system indicates plasticity changes in the neural representation of sound resulting from listening to an enriched auditory signal. Further investigation of longer training or auditory experiences with favorable listening conditions is needed to determine if that results in long-term speech-perception-in-noise benefits.

Mapping Tree Canopy in Urban Environments Using Point Clouds from Airborne Laser Scanning and Street Level Imagery.

Resilient cities incorporate a social, ecological, and technological systems perspective through their trees, both in urban and peri-urban forests and linear street trees, and help promote and understand the concept of ecosystem resilience. Urban tree inventories usually involve the collection of field data on the location, genus, species, crown shape and volume, diameter, height, and health status of these trees. In this work, we have developed a multi-stage methodology to update urban tree inventories in a fully automatic way, and we have applied it in the city of Pamplona (Spain). We have compared and combined two of the most common data sources for updating urban tree inventories: Airborne Laser Scanning (ALS) point clouds combined with aerial orthophotographs, and street-level imagery from Google Street View (GSV). Depending on the data source, different methodologies were used to identify the trees. In the first stage, the use of individual tree detection techniques in ALS point clouds was compared with the detection of objects (trees) on street level images using computer vision (CV) techniques. In both cases, a high success rate or recall (number of true positive with respect to all detectable trees) was obtained, where between 85.07% and 86.42% of the trees were well-identified, although many false positives (FPs) or trees that did not exist or that had been confused with other objects were always identified. In order to reduce these errors or FPs, a second stage was designed, where FP debugging was performed through two methodologies: (a) based on the automatic checking of all possible trees with street level images, and (b) through a machine learning binary classification model trained with spectral data from orthophotographs. After this second stage, the recall decreased to about 75% (between 71.43 and 78.18 depending on the procedure used) but most of the false positives were eliminated. The results obtained with both data sources were robust and accurate. We can conclude that the results obtained with the different methodologies are very similar, where the main difference resides in the access to the starting information. While the use of street-level images only allows for the detection of trees growing in trafficable streets and is a source of information that is usually paid for, the use of ALS and aerial orthophotographs allows for the location of trees anywhere in the city, including public and private parks and gardens, and in many countries, these data are freely available.

Flower Extracts from Ornamental Plants as Sources of Sunscreen Ingredients: Determination by In Vitro Methods of Photoprotective Efficacy, Antigenotoxicity and Safety.

Plants are sources of sunscreen ingredients that prevent cellular mutations involved in skin cancer and aging. This study investigated the sunscreen properties of the extracts from some ornamental plants growing in Colombia. The UV filter capability of the flower extracts obtained from Rosa centifolia L., Posoqueria latifolia (Rudge) Schult, and Ipomoea horsfalliae Hook. was examined. Photoprotection efficacies were evaluated using in vitro indices such as sun protection factor and critical wavelength. UVB antigenotoxicity estimates measured with the SOS Chromotest were also obtained. Extract cytotoxicity and genotoxicity were studied in human fibroblasts using the trypan blue exclusion and Comet assays, respectively. Major compounds of the promising flower extracts were identified by UHPLC-ESI+-Orbitrap-MS. The studied extracts showed high photoprotection efficacy and antigenotoxicity against UVB radiation, but only the P. latifolia extract showed broad-spectrum photoprotection at non-cytotoxic concentrations. The P. latifolia extract appeared to be safer for human fibroblast cells and the R. centifolia extract was shown to be moderately cytotoxic and genotoxic at the highest assayed concentrations. The I. horsfalliae extract was unequivocally cytotoxic and genotoxic. The major constituents of the promising extracts were as follows: chlorogenic acid, ecdysterone 20E, rhamnetin-rutinoside, cis-resveratrol-diglucoside, trans-resveratrol-diglucoside in P. latifolia; quercetin, quercetin-glucoside, quercetin-3-rhamnoside, kaempferol, kaempferol-3-glucoside, and kaempferol-rhamnoside in R. centifolia. The potential of the ornamental plants as sources of sunscreen ingredients was discussed.

Quantum Information Entropies on Hyperbolic Single Potential Wells.

In this work, we study the quantum information entropies for two different types of hyperbolic single potential wells. We first study the behaviors of the moving particle subject to two different hyperbolic potential wells through focusing on their wave functions. The shapes of these hyperbolic potentials are similar, but we notice that their momentum entropy densities change along with the width of each potential and the magnitude of position entropy density decreases when the momentum entropy magnitude increases. On the other hand, we illustrate the behaviors of their position and momentum entropy densities. Finally, we show the variation of position and momentum entropies Sx and Sp with the change of the potential well depth u and verify that their sum still satisfies the BBM inequality relation.

Therapeutic plasmapheresis for the treatment of thyrotoxicosis: A retrospective multi-center study.

BACKGROUND AND AIMS: Thyroid storm and severe thyrotoxicosis remain among the most frequent endocrine emergencies, and first-line hyperthyroidism treatment is not always an option. Since the first report in 1970, plasmapheresis is a second-line treatment for severe or otherwise untreatable thyrotoxicosis when rapid euthyroidism is desired. METHODS: We present a retrospective study of the experience in treating thyrotoxicosis with plasmapheresis between 2012 and 2020 in two specialized centers in Colombia. We register the demographic and clinical characteristic and compare the thyroid hormones and other biochemical measurements before and after treatment. RESULTS: Data from 19 patients was obtained, 58% female with a median age of 35 years (IQR 23.5), and most of them with Graves' disease. The most frequent indication for plasmapheresis was thyroid storm. A median of 4 (IQR 2) sessions lead to a significant reduction in FT4 (P .0001) and TT3 (P < .0003) with a nonsignificant decrease in beta-blocker (P .7353) dose, no change in hepatic enzymes, and no adverse events. After plasmapheresis, thyroidectomy was performed in 10 patients. CONCLUSIONS: Plasmapheresis is an effective and safe treatment option for reducing circulating thyroid hormones in severe thyrotoxicosis when other forms of treatment are contraindicated or in case of urgent thyroid and non-thyroid surgery. It is limited by its cost and the need for highly specialized resources.

The Challenge of Listening at Home: Speech and Noise Levels in Homes of Young Children With Hearing Loss.

OBJECTIVES: The objective of this study was to characterize the acoustics of the home environment of young children with hearing loss. Specifically, we aimed to quantify the range of speech levels, noise levels, and signal-to-noise ratios (SNRs) encountered by children with hearing loss in their homes. DESIGN: Nine families participated in the study. The children with hearing loss in these families were between 2 and 5 years of age. Acoustic recordings were made in the children's homes over one weekend (Saturday and Sunday) using Language ENvironmental Analysis (LENA) recorders. These recordings were analyzed using LENA's proprietary software to determine the range of speech and noise levels in the child's home. A custom Matlab program analyzed the LENA output to estimate the SNRs in the children's homes. RESULTS: The average SNR encountered by children with hearing loss in our sample was approximately +7.9 dB SNR. It is important to note that our analyses revealed that approximately 84% of the SNRs experienced by these children with hearing loss were below the +15 dB SNR recommended by the American Speech-Language Hearing Association. Averaged across families, speech and noise levels were 70.1 and 62.2 C-weighted decibels, respectively. CONCLUSIONS: These data show that, for much of the time, young children with hearing loss are forced to listen under suboptimal conditions in their home environments. This has important implications as listening under these conditions could negatively affect learning opportunities for young children with hearing loss. To mitigate these potential negative effects, the use of assistive listening devices that improve the SNR (e.g., remote microphone systems) should be considered for use at home by young children with hearing loss.

Keystone flap: a safe coverage option in the handling of salvage for myelomeningocele.

BACKGROUND: Myelomeningocele (MMC) is the most common and severe pathology of open spina bifida compatible with life. Its early closure is an urgent therapeutic objective to reduce the morbidity and mortality of neonates, being a surgical challenge with two major objectives: (1) achieve closure of the dural cerebrum-spinal fluid fistula and (2) ensure a stable and durable soft tissue coverage. The use of fasciocutaneous flaps in keystone design is shown as a safe and stable surgical option with excellent aesthetic results in patients with MMC and who presented failed primary closures. METHODS: Two clinical cases of fasciocutaneous flaps in keystone design were described as a coverage option in patients with lumbosacral MMC, in whom the primary closure was unsuccessful and required a safe coverage as a priority. RESULTS: Successful coverage of the lumbosacral defect was performed using keystone flaps in neonatal patients with MMC and previous manipulation of the soft tissues when attempting primary closure, but they have had dehiscence of the wound, with a large area of lumbosacral defect and sizeable defect/back ratio. CONCLUSIONS: The use of keystone flaps is a useful, accessible, and versatile technique as a management option for lumbosacral coverage defects in MMC, achieving a stable and safe covering of the meninges, without cerebrum-spinal fluid fistulas, which also allows the primary closure of the soft tissues in the donor area. The safety of this type of flap when used as salvage in lumbosacral defects with previously handled and raised tissues could infer that it is reliable enough to be considered as a first surgical option in the initial management of MMC.

Identifying Drugs that Bind Selectively to Intersubunit General Anesthetic Sites in the α1ß3γ2 GABAAR Transmembrane Domain.

GABAA receptors (GABAARs) are targets for important classes of clinical agents (e.g., anxiolytics, anticonvulsants, and general anesthetics) that act as positive allosteric modulators (PAMs). Previously, using photoreactive analogs of etomidate ([3H]azietomidate) and mephobarbital [[3H]1-methyl-5-allyl-5-(m-trifluoromethyl-diazirynylphenyl)barbituric acid ([3H]R-mTFD-MPAB)], we identified two homologous but pharmacologically distinct classes of general anesthetic binding sites in the α1ß3γ2 GABAAR transmembrane domain at ß +-α - (ß + sites) and α +-ß -/γ +-ß - (ß - sites) subunit interfaces. We now use competition photolabeling with [3H]azietomidate and [3H]R-mTFD-MPAB to identify para-substituted propofol analogs and other drugs that bind selectively to intersubunit anesthetic sites. Propofol and 4-chloro-propofol bind with 5-fold selectivity to ß +, while derivatives with bulkier lipophilic substitutions [4-(tert-butyl)-propofol and 4-(hydroxyl(phenyl)methyl)-propofol] bind with ∼10-fold higher affinity to ß - sites. Similar to R-mTFD-MPAB and propofol, these drugs bind in the presence of GABA with similar affinity to the α +-ß - and γ +-ß - sites. However, we discovered four compounds that bind with different affinities to the two ß - interface sites. Two of these bind with higher affinity to one of the ß - sites than to the ß + sites. We deduce that 4-benzoyl-propofol binds with >100-fold higher affinity to the γ +-ß - site than to the α +-ß - or ß +-α - sites, whereas loreclezole, an anticonvulsant, binds with 5- and 100-fold higher affinity to the α +-ß - site than to the ß + and γ +-ß - sites. These studies provide a first identification of PAMs that bind selectively to a single intersubunit site in the GABAAR transmembrane domain, a property that may facilitate the development of subtype selective GABAAR PAMs.

Supplemental Fixation of Inner Graft Limbs in All-Inside, Quadrupled, Single-Tendon Anterior Cruciate Ligament Reconstruction Graft Construct Yields Improved Biomechanical Properties.

PURPOSE: To compare the time-zero load to failure of a quadrupled, single-tendon, all-inside anterior cruciate ligament (ACL) reconstruction graft construct with (supplemented) and without the incorporation of inner-limb whipstitch sutures (control) into a tibial suspensory fixation button. METHODS: Eight matched pairs of peroneus longus tendons were prepared according to a quadrupled, all-inside ACL soft-tissue graft technique with 1 side serving as a control and the contralateral side supplemented. The constructs were biomechanically tested for strain in the inner and outer limbs during a preconditioning protocol, single-cycle load to failure, and elongation of the whole construct. RESULTS: Ultimate load to failure was significantly higher in the supplemented group: 797.5 ± 49.6 N (95% confidence interval [CI], 763.13-831.87 N) versus 719.6 ± 69.6 N (95% CI, 671.38-767.82 N; P = .044). Less graft elongation at failure was observed in the supplemented group (3.1 ± 1.5 mm; 95% CI, 2.07-4.17 mm) versus the control group (21.0 ± 21.2 mm; 95% CI, 6.31-35.69 mm; P = .052). The number of grafts undergoing a 5-mm or greater change in length at failure was 1 of 8 in the supplemented group versus 5 of 8 in the control group (P = .038). CONCLUSIONS: Inner-limb supplemental tibial fixation results in higher time-zero load to failure and decreased graft elongation in a quadrupled, single-tendon, all-inside ACL reconstruction graft construct. CLINICAL RELEVANCE: The weak point of a single-tendon, quadrupled, all-inside ACL graft construct is the tendon-to-tendon suturing to secure the inner limbs of the graft. Adding supplemental fixation by incorporating the sutures from the inner limb to the tibial suspensory fixation button leads to a higher time-zero load to failure and decreased graft elongation.

Bilingual Versus Monolingual Vocabulary Instruction for Bilingual Children with Hearing Loss.

Effective vocabulary interventions for children with hearing loss, including children who are bilingual, are needed because of persistent vocabulary deficits in this population. Current instructional practices for children with hearing loss who are bilingual vary in the degree to which they incorporate the language the child uses at home. Unfortunately, there is little direct evidence as to whether bilingual or monolingual instructional practices yield greater benefits for these children. Three Spanish-English-speaking children participated in this single case adapted alternating treatments design study that evaluated the effectiveness and efficiency of bilingual and monolingual teaching procedures for an expressive vocabulary intervention. Contrary to predictions from a monolingual instruction perspective, no evidence of an inhibitory effect of bilingual instruction on English performance was identified. Participants exhibited gains in Spanish for words in the bilingual condition only. Findings suggest more efficient word learning in the bilingual condition as measured by conceptual vocabulary.

MRI findings in bucket-handle tears of the triangular fibrocartilage complex.

The triangular fibrocartilage complex (TFCC) is an intricate ligamentous and cartilaginous structure that helps transmit axial load across the wrist, and provide stability to the ulnocarpal and distal radioulnar joints (DRUJ). Because the blood supply to the TFCC varies depending on location, certain types of tears are more amenable to surgical repair than others. Since Palmer proposed his classification system of TFCC tears in 1989, only 1 case of a "bucket-handle" type tear has been reported. In this article, we describe two new cases of bucket-handle tears of the TFCC. In both cases, the torn fragment was displaced into a previously undescribed location (intra-articular DRUJ and prestyloid recess). Because this type of injury pattern has not been previously well characterized in the literature and such cases rarely reported, MRI findings have not been fully described and its implications on clinical management have largely yet to be determined.

Stereoselective Traceless Borylation-Allenation of Propargylic Epoxides: Dual Role of the Copper Catalyst.

Chiral α-allenols are prepared with high diastereocontrol through an unprecedented and spontaneous ß-oxygen elimination of an α-epoxy vinyl boronate. Stochiometric experiments and DFT calculations support a dual role of the copper catalyst, which orchestrates the hydroboration and the syn-elimination step.

Calcitriol-mediated hypercalcemia secondary to granulomatous disease caused by soft-tissue filler injection: a case report.

Soft-tissue filler (STF) injections have been used worldwide for cosmetic reasons. In most cases, they are not approved by the United States Food and Drug Administration (FDA). Regulatory boards in Latin American countries do not allow the medical use of STF injections; however, these injections are still widely used. A case of calcitriol-mediated hypercalcemia with ectopic calcifications, chronic kidney disease, nephrolithiasis and calcinosis is presented. The reported case highlights the consequences of STF use, including calcitriol-mediated hypercalcemia secondary to granulomatous reactions years after an esthetic procedure.

Perforin-2 Protects Host Cells and Mice by Restricting the Vacuole to Cytosol Transitioning of a Bacterial Pathogen.

The host-encoded Perforin-2 (encoded by the macrophage-expressed gene 1, Mpeg1), which possesses a pore-forming MACPF domain, reduces the viability of bacterial pathogens that reside within membrane-bound compartments. Here, it is shown that Perforin-2 also restricts the proliferation of the intracytosolic pathogen Listeria monocytogenes Within a few hours of systemic infection, the massive proliferation of L. monocytogenes in Perforin-2(-/-)mice leads to a rapid appearance of acute disease symptoms. We go on to show in cultured Perforin-2(-/-)cells that the vacuole-to-cytosol transitioning of L. monocytogenesis greatly accelerated. Unexpectedly, we found that in Perforin-2(-/-)macrophages,Listeria-containing vacuoles quickly (≤ 15 min) acidify, and that this was coincident with greater virulence gene expression, likely accounting for the more rapid translocation of L. monocytogenes to its replicative niche in the cytosol. This hypothesis was supported by our finding that aL. monocytogenes strain expressing virulence factors at a constitutively high level replicated equally well in Perforin-2(+/+)and Perforin-2(-/-)macrophages. Our findings suggest that the protective role of Perforin-2 against listeriosis is based on it limiting the intracellular replication of the pathogen. This cellular activity of Perforin-2 may derive from it regulating the acidification of Listeria-containing vacuoles, thereby depriving the pathogen of favorable intracellular conditions that promote its virulence gene activity.

Seco-limonoid derived from Raputia heptaphylla promotes the control of cutaneous leishmaniasis in hamsters (Mesocricetus auratus).

The rational search of novel bioactive molecules against pathogens with immunomodulatory activity is presently one of the most significant approaches to discover and design new therapeutic agents for effective control of infectious diseases, such as the infection caused by Leishmania parasites. In the present study, we evaluated the therapeutic efficacy of the recently characterized immunomodulatory compound 11α,19ß-dihydroxy-7-acetoxy-7-deoxoichangin, a seco-limonoid derived from the bark of Raputia heptaphylla (Pittier) using: (1) peritoneal macrophages and (2) Mesocricetus auratus hamsters infected with Leishmania (V.) panamensis and Leishmania (L.) amazonensis. We observed the ability of this seco-limonoid to induce the effective control of the parasite either in vitro [determining an effective concentration 50 (EC50) of 59 µ m at the infection model] and in vivo (inducing clinical improvement or even cure in infected animals treated compared with the groups of animals treated with vehicle solution or meglumine antimoniate).