Generation of hiPSC-Derived Intestinal Organoids for Developmental and Disease Modelling Applications.

hiPSC-derived intestinal organoids are epithelial structures that self-assemble from differentiated cells into complex 3D structures, representative of the human intestinal epithelium, in which they exhibit crypt/villus-like structures. Here, we describe the generation of hiPSC-derived intestinal organoids by the stepwise differentiation of hiPSCs into definitive endoderm, which is then posteriorized to form hindgut epithelium before being transferred into 3D culture conditions. The 3D culture environment consists of extracellular matrix (ECM) (e.g., Matrigel or other compatible ECM) supplemented with SB202190, A83-01, Gastrin, Noggin, EGF, R-spondin-1 and CHIR99021. Organoids undergo passaging every 7 days, where they are mechanically disrupted before transfer to fresh extracellular matrix and allowed to expand. QPCR and immunocytochemistry confirm that hiPSC-derived intestinal organoids contain mature intestinal epithelial cell types including goblet cells, Paneth cells and enterocytes. Additionally, organoids show evidence of polarization by expression of villin localized on the apical surface of epithelial cells. The resulting organoids can be used to model human intestinal development as well as numerous human intestinal diseases including inflammatory bowel disease. To model intestinal inflammation, organoids can be exposed to inflammatory mediators such as TNF-α, TGF-ß, and bacterial LPS. Organoids exposed to proinflammatory cytokines display an inflammatory and fibrotic phenotype in response. Pairing of healthy versus hiPSCs derived from patients with IBD may be useful in understanding mechanisms driving IBD. This may reveal novel therapeutic targets and novel biomarkers to assist in early disease diagnosis.

Conservative kidney management and kidney supportive care: core components of integrated care for people with kidney failure.

Integrated kidney care requires synergistic linkage between preventative care for people at risk for chronic kidney disease and health services providing care for people with kidney disease, ensuring holistic and coordinated care as people transition between acute and chronic kidney disease and the 3 modalities of kidney failure management: conservative kidney management, transplantation, and dialysis. People with kidney failure have many supportive care needs throughout their illness, regardless of treatment modality. Kidney supportive care is therefore a vital part of this integrated framework, but is nonexistent, poorly developed, and/or poorly integrated with kidney care in many settings, especially in low- and middle-income countries. To address this, the International Society of Nephrology has (i) coordinated the development of consensus definitions of conservative kidney management and kidney supportive care to promote international understanding and awareness of these active treatments; and (ii) identified key considerations for the development and expansion of conservative kidney management and kidney supportive care programs, especially in low resource settings, where access to kidney replacement therapy is restricted or not available. This article presents the definitions for conservative kidney management and kidney supportive care; describes their core components with some illustrative examples to highlight key points; and describes some of the additional considerations for delivering conservative kidney management and kidney supportive care in low resource settings.

Primeras recomendaciones de consenso SLANH - COLABIOCLI / Primeiras Recomendações de Consenso SLANH - COLABIOCLI / (Sociedad Latinoamericana de Nefrología e Hipertensión - Confederación Latinoamericana de Bioquímica Clínica) / Informe de la tasa de filtración glomerular estimada junto a la determinación de la creatininemia en población adulta / First SLANH-COLABIOCLI Consensus Recommendations

Resumen La enfermedad renal crónica (ERC) es de alta prevalencia en América Latina y en todo el mundo. Se estima que entre 10 y 20% de la población adulta es portadora de ERC y su prevalencia va en aumento. La ERC progresa en forma silenciosa. Su diagnóstico temprano y oportuno permite iniciar un tratamiento efectivo, en la mayoría de los casos, para detener la enfermedad. Desde hace mucho tiempo, el análisis de la creatininemia es la principal prueba utilizada para valorar la función renal, pero su confiabilidad es limitada. De acuerdo con las recomendaciones de las GUIAS KDOQI del año 2002 la tasa de filtración glomerular estimada (TFGe) obtenida a través de fórmulas, se estableció como una de las herramientas principales para detectar la enfermedad renal de manera precoz, ya que alerta de forma precisa al médico y al equipo de salud sobre el nivel de función renal del paciente. La detección de una TFGe disminuida (menor de 60 mL/min/1,73 m2) es clínicamente relevante, ya que permite establecer el diagnóstico de enfermedad renal en adultos. En el año 2022, en una encuesta realizada por SLANH y COLABIOCLI dirigida a los laboratorios de análisis clínicos de América Latina (n: 237), el 49% de los mismos no informaban la TFGe rutinariamente. En base a esta realidad SLANH y COLABIOCLI elaboraron estas recomendaciones de consenso en referencia al uso de la TFGe.

Abstract Chronic kidney disease (CKD) has a high prevalence worldwide and in Latin America (10 to 20% of the adult population) and is increasing. CKD progresses silently. Opportune diagnosis and treatment are effective in most cases to improve outcomes. Serum creatinine was the main test to assess kidney function, but its reliability is limited. Through the KDOQI Guidelines 2002, the estimated glomerular filtration rate (eGFR) obtained from equations was established as one of the main tools for the early detection of kidney disease in clinical practice. The detection of a decreased eGFR (less than 60 mL/min/1.73 m2) is clinically relevant. This cut-off level establishes the diagnosis of kidney disease in adults. In 2022 SLANH and COLABIOCLI conducted a survey among the clinical laboratories from Latin America. The survey included 237 laboratories, 49% of which did not routinely report the eGFR. Based on this situation, SLANH and COLABIOCLI have elaborated the following consensus recommendations regarding the use of eGFR.

Resumo A doença renal crônica (DRC) é altamente prevalente na América Latina e em todo o mundo. Estima-se que entre 10 e 20% da população adulta seja portadora de DRC e sua prevalência esteja aumentando. A DRC progride silenciosamente. Seu diagnóstico precoce e oportuno permite iniciar um tratamento eficaz, na maioria dos casos, para estancar a doença. Faz muito tempo, a análise da creatinina tem sido o principal teste usado para avaliar a função renal mas sua confiabilidade é limitada. De acordo com as recomendações dos GUIAS KDOQI do ano de 2002, a estimativa da taxa de filtração glomerular (eGFR), obtida por meio de fórmulas, consolidou-se como uma das principais ferramentas para a detecção precoce da doença renal, visto que alerta com precisão ao médico e ao equipe de saúde sobre o nível de função renal do paciente. A detecção de uma eGFR diminuída (inferior a 60 mL/min/1,73 m2) é clinicamente relevante, pois permite estabelecer o diagnóstico de doença renal em adultos. No ano de 2022, em pesquisa realizada pela SLANH e COLABIOCLI dirigida a laboratórios de análises clínicas da América Latina (n: 237), 49% deles não relataram rotineiramente eGFR. Com base nessa realidade, SLANH e COLABIOCLI prepararam essas recomendações de consenso sobre o uso de eGFR.

Fatal Outcome After Reduction of a Superior Shoulder Dislocation, A Case Report and Literature Review: A Case Report and Literature Review.

CASE: An 81-year-old woman presented a superior glenohumeral dislocation after a low-energy fall, with a mechanism of axial load while the shoulder was in adduction and extension. After successful closed reduction, the patient presented sudden symptoms of severe vascular injury with a protruding axillary hematoma and hypovolemic shock. CONCLUSION: Superior shoulder dislocations and vascular injuries are extremely rare among shoulder dislocations, especially after low-energy trauma. Vascular injuries may result in limb compromise and death. We highlight the importance of high clinical suspicion, particularly in superior dislocations, and the importance of prompt management of vascular complications to avoid catastrophic outcomes.

Fractal and Polarization Properties of Light Scattering Using Microcrystalline Pharmaceutical Aggregates.

Fractal and polarization analysis of diffusively scattered light is applied to determine the complex relationship between fractal dimension of structural morphology and concentration of chemically active ingredients in two pharmaceutical mixture systems including a series of binary mixtures of acetaminophen in lactose and three multicomponent blends with a proprietary active ingredient. A robust approach is proposed to identify and filter out multiple- and single-scattering components of scattering indicatrix. The fractal dimension extracted from scattering field reveals complex structural details of the sample, showing strong dependence on low-dose drug concentration in the blend. Low-angle diffraction shows optical "halo" patterns near the angle of specular reflection caused by light refraction in microcrystalline aggregates. Angular measurements of diffuse reflection demonstrate noticeable dependence of Brewster's angle on drug concentration. It is shown that the acetaminophen microcrystals produce scattered light depolarization due to their optical birefringence. The light scattering measurement protocol developed for diffusively scattered light by microcrystalline pharmaceutical compositions provides a novel approach for the pattern recognition, analysis and classification of materials with a low concentration of active chemical ingredients.

Challenges for sustainable end-stage kidney disease care in low-middle-income countries: the problem of the workforce.

Prevention and early detection of kidney diseases in adults and children should be a priority for any government health department. This is particularly pertinent in the low-middle-income countries, mostly in Asia, Africa, Latin America, and the Caribbean, where up to 7 million people die because of lack of end-stage kidney disease treatment. The nephrology workforce (nurses, technicians, and doctors) is limited in these countries and expanding the size and expertise of the workforce is essential to permit expansion of treatment for both chronic kidney disease and end-stage kidney disease. To achieve this will require sustained action and commitment from governments, academic medical centers, local nephrology societies, and the international nephrology community.

Supportive care for end-stage kidney disease: an integral part of kidney services across a range of income settings around the world.

A key component of treatment for all people with advanced kidney disease is supportive care, which aims to improve quality of life and can be provided alongside therapies intended to prolong life, such as dialysis. This article addresses the key considerations of supportive care as part of integrated end-stage kidney disease care, with particular attention paid to programs in low- and middle-income countries. Supportive care should be an integrated component of care for patients with advanced chronic kidney disease, patients receiving kidney replacement therapy (KRT), and patients receiving non-KRT conservative care. Five themes are identified: improving information on prognosis and support, developing context-specific evidence, establishing appropriate metrics for monitoring care, clearly communicating the role of supportive care, and integrating supportive care into existing health care infrastructures. This report explores some general aspects of these 5 domains, before exploring their consequences in 4 health care situations/settings: in people approaching end-stage kidney disease in high-income countries and in low- and middle-income countries, and in people discontinuing KRT in high-income countries and in low- and middle-income countries.

Method transfer of a near-infrared spectroscopic method for blend uniformity in a poorly flowing and hygroscopic blend.

The challenges in transferring and executing a near-infrared (NIR) spectroscopic method for croscarmellose (disintegrant) in binary blends for a continuous manufacturing (CM) process are presented. This work demonstrates the development of a NIR calibration model and its use to determine the blending parameters needed for binary blends at a development plant and later used to predict CM process blends. The calibration models were developed with laboratory scale powder blends ranging from 4.32%-64.77 (%w/w) of croscarmellose and evaluated using independent test blends. The selected model was then transferred to the continuous manufacturing development site to determine the croscarmellose concentration for spectra collected in real-time. A total of 18 development plant runs were monitored using an in-line NIR spectrometer, however, these spectra showed high baseline variations. The baseline variations were caused by the poor flow of the material within the system. An inconsistent bias which varied from 2.51 to 14.95 (%w/w) was observed in the predictions of croscarmellose. High baseline spectra were eliminated and the bias was significantly reduced by 42-51%. Experiments at lower flow rate speeds did not show significant changes in baseline and bias values showed more consistency. The calibration model was then transferred to two NIR spectrometers installed at-line at the commercial site, where powder samples were collected at the beginning middle and end of each CM plant run. The NIR calibration model predicted disintegrant concentration from the powder samples. Results showed the bias values for the NIR (1) varied from 0.74 to 2.21 (%w/w) and NIR (2) from 0.28 to 3.39 (%w/w). Average concentration values for both equipments were very close to the reference concentration values of 43.18 and 50.98 (%w/w). The study showed the model was able to identify flow issues, identified as baseline shifts, that could be used to alert to problems in the powder bed that may warrant diversion from a production line. These powder flow problems such as air gaps and inconsistent powder bed height affected the NIR spectra collected at the development plant and provided results with high bias. A lower bias was obtained in samples collected at line after blending.

Increasing access to integrated ESKD care as part of universal health coverage.

The global nephrology community recognizes the need for a cohesive strategy to address the growing problem of end-stage kidney disease (ESKD). In March 2018, the International Society of Nephrology hosted a summit on integrated ESKD care, including 92 individuals from around the globe with diverse expertise and professional backgrounds. The attendees were from 41 countries, including 16 participants from 11 low- and lower-middle-income countries. The purpose was to develop a strategic plan to improve worldwide access to integrated ESKD care, by identifying and prioritizing key activities across 8 themes: (i) estimates of ESKD burden and treatment coverage, (ii) advocacy, (iii) education and training/workforce, (iv) financing/funding models, (v) ethics, (vi) dialysis, (vii) transplantation, and (viii) conservative care. Action plans with prioritized lists of goals, activities, and key deliverables, and an overarching performance framework were developed for each theme. Examples of these key deliverables include improved data availability, integration of core registry measures and analysis to inform development of health care policy; a framework for advocacy; improved and continued stakeholder engagement; improved workforce training; equitable, efficient, and cost-effective funding models; greater understanding and greater application of ethical principles in practice and policy; definition and application of standards for safe and sustainable dialysis treatment and a set of measurable quality parameters; and integration of dialysis, transplantation, and comprehensive conservative care as ESKD treatment options within the context of overall health priorities. Intended users of the action plans include clinicians, patients and their families, scientists, industry partners, government decision makers, and advocacy organizations. Implementation of this integrated and comprehensive plan is intended to improve quality and access to care and thereby reduce serious health-related suffering of adults and children affected by ESKD worldwide.

Development of near infrared spectroscopic calibration models for in-line determination of low drug concentration, bulk density, and relative specific void volume within a feed frame.

This study describes the development of a near infrared (NIR) calibration model for real time determination of drug concentration, powder density, and porosity or relative specific void volume (RSVV) of 3.00%w/w acetaminophen blends within a feed frame. The NIR calibration model was developed from 1.50 to 4.50%w/w of acetaminophen, using a high variability of major excipients (from 12.92 to 81.95%w/w) which facilitates the prediction of powder density and RSVV based on near infrared calibration spectra. The model using second derivative as spectral preprocessing explained the changes related to acetaminophen concentration in the first latent variable. The second latent variable was related to changes in concentration of microcrystalline cellulose and lactose in the powder blends. NIR calibrations were also developed based on the bulk density and RSVV of the powder blends using the same design as the API model, due to the physical properties of the particles and their effects on the NIR spectra. The RSVV was predicted for the independent set blends with an RSEP(%) below 4% with a significantly low bias (0.04 cm3/g) from reference values of 1.33 to 1.58 cm3/g. The bulk density model also exhibited excellent predictions with RSEP(%) below 2.6% and significantly low bias (0.01 g/cm3) from reference values of 0.45 to 0.51 g/cm3. The excellent results obtained show the potential of near infrared spectroscopic measurements within the feed frame for a Process Analytical Technology method to control the critical properties such as tablet mass, hardness and dissolution in batch and continuous manufacturing processes.

Thermal Jeans Fragmentation within ~ 1000 AU in OMC-1S.

We present subarcsecond 1.3 mm continuum ALMA observations towards the Orion Molecular Cloud 1 South (OMC-1S) region, down to a spatial resolution of 74 AU, which reveal a total of 31 continuum sources. We also present subarcsecond 7 mm continuum VLA observations of the same region, which allow to further study fragmentation down to a spatial resolution of 40 AU. By applying a Mean Surface Density of Companions method we find a characteristic spatial scale at ~ 560 AU, and we use this spatial scale to define the boundary of 19 'cores' in OMC-1S as groupings of millimeter sources. We find an additional characteristic spatial scale at ~ 2900 AU, which is the typical scale of the filaments in OMC-1S, suggesting a two-level fragmentation process. We measured the fragmentation level within each core and find a higher fragmentation towards the southern filament. In addition, the cores of the southern filament are also the densest (within 1100 AU) cores in OMC-1S. This is fully consistent with previous studies of fragmentation at spatial scales one order of magnitude larger, and suggests that fragmentation down to 40 AU seems to be governed by thermal Jeans processes in OMC-1S.

A molecular docking study of the interactions between human transferrin and seven metallocene dichlorides.

Human Transferrin (hTf) is a metal-binding protein found in blood plasma and is well known for its role in iron delivery. With only a 30% of its capacity for Fe+3 binding, this protein has the potential ability to transport other metal ions or organometallic compounds from the blood stream to all cell tissues. In this perspective, recent studies have described seven metallocene dichlorides (Cp2M(IV)Cl2, M(IV)=V, Mo, W, Nb, Ti, Zr, Hf) suitable as anticancer drugs and less secondary effects than cisplatin. However, these studies have not provided enough data to clearly explain how hTf binds and transports these organometallic compounds into the cells. Thus, a computational docking study with native apo-hTf using Sybyl-X 2.0 program was conducted to explore the binding modes of these seven Cp2M(IV)Cl2 after their optimization and minimization using Gaussian 09. Our model showed that the first three Cp2M(IV)Cl2 (M(IV)=V, Mo, W) can interact with apo-hTf on a common binding site with the amino acid residues Leu-46, Ile-49, Arg-50, Leu-66, Asp-69, Ala-70, Leu-72, Ala-73, Pro-74 and Asn-75, while the next four Cp2M(IV)Cl2 (M(IV)=Nb, Ti, Zr, Hf) showed different binding sites, unknown until now. A decreasing order in the total score (equal to -log Kd) was observed from these docking studies: W (5.4356), Mo (5.2692), Nb (5.1672), V (4.5973), Ti (3.6529), Zr (2.0054) and Hf (1.8811). High and significant correlation between the affinity of these seven ligands (metallocenes) for apo-hTf and their bond angles CpMCp (r=0.94, p<0.01) and Cl-M-Cl (r=0.95, p<0.01) were observed, thus indicating the important role that these bond angles can play in ligand-protein interactions. Fluorescence spectra of apo-hTf, measured at pH 7.4, had a decrease in the fluorescence emission spectrum with increasing concentration of Cp2M(IV)Cl2. Experimental data has a good correlation between KA (r=0.84, p=0.027) and Kd (r=0.94, p=0.0014) values and the calculated total scores obtained from our docking experiments. In conclusion, these results suggest that the seven Cp2M(IV)Cl2 used for this study can interact with apo-hTf, and their affinity was directly and inversely proportional to their bond angles CpMCp and ClMCl, respectively. Our docking studies also suggest that the binding of the first three Cp2M(IV)Cl2 (M(IV)=V, Mo, W) to hTf could abrogate the formation of the hTf-receptor complex, and as a consequence the metallocene-hTf complex might require another transport mechanism in order to get into the cell.

Near infrared spectroscopic calibration models for real time monitoring of powder density.

Near infrared spectroscopic (NIRS) calibration models for real time prediction of powder density (tap, bulk and consolidated) were developed for a pharmaceutical formulation. Powder density is a critical property in the manufacturing of solid oral dosages, related to critical quality attributes such as tablet mass, hardness and dissolution. The establishment of calibration techniques for powder density is highly desired towards the development of control strategies. Three techniques were evaluated to obtain the required variation in powder density for calibration sets: 1) different tap density levels (for a single component), 2) generating different strain levels in powders blends (and as consequence powder density), through a modified shear Couette Cell, and 3) applying normal forces during a compressibility test with a powder rheometer to a pharmaceutical blend. For each variation in powder density, near infrared spectra were acquired to develop partial least squares (PLS) calibration models. Test samples were predicted with a relative standard error of prediction of 0.38%, 7.65% and 0.93% for tap density (single component), shear and rheometer respectively. Spectra obtained in real time in a continuous manufacturing (CM) plant were compared to the spectra from the three approaches used to vary powder density. The calibration based on the application of different strain levels showed the greatest similarity with the blends produced in the CM plant.

Management of burst fractures in the thoracolumbar spine.

UNLABELLED: The most common fractures in the spine take place in the thoracolumbar region. Currently there is no consensus regarding optimum treatment. OBJECTIVE: Analyze the current medical literature available regarding treatment of compression fractures of the thoracolumbar spine. METHODS: Research of current literature in medical databases. RESULTS: Regarding current available literature, we found no consensus in the treatment of compression fractures in the thoracolumbar spine. CONCLUSIONS: Burst fractures of the thoracolumbar junction is a very common condition, treatment of each patient must be individualized. Conservative treatment is recommended for stable fractures without neurological compromise and less than 35° of kyphosis.

Long-Term High-Temperature Stability of Functionalized Graphene Oxide Nanoplatelets in Arab-D and API Brine.

Partially reduced graphene oxide (prGO) was covalently functionalized with a zwitterionic polymer polyzwitterionic polymer to afford a composite material with excellent dispersibility and long-term stability in high salinity brines including standard API and Arab-D found in deep oil reservoirs. When heated at 90 °C, the dispersions remained stable in excess of 140 days. These results suggest the utility of imidazolium-based polymers for brine stabilization as well as the use of diazonium containing polymers for a "grafting-to" approach to nanocarbon functionalization.

Water soluble molybdenocene complexes: synthesis, cytotoxic activity and binding studies to ubiquitin by fluorescence spectroscopy, circular dichroism and molecular modeling.

Four new molybdenocene complexes, Cp2Mo(l-ascorbato), Cp2Mo(6-O-palmitoyl-l-ascorbato), [Cp2Mo(ethyl maltolato)]Cl and Cp2Mo((2S)-2-amino-3-methyl-3-thiolato-butanoato), were synthesized and structurally characterized by standard analytical methods. The cytotoxicity of these complexes was assessed on colon HT-29 and breast MCF-7 cancer cell lines using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. A higher cytotoxic activity was shown by all the new complexes on the MCF-7 cells over the Cp2MoCl2 complex. The complexes Cp2Mo(l-ascorbato), Cp2Mo(6-O-palmitoyl-l-ascorbato) and [Cp2Mo(ethyl maltolato)]Cl displayed a stronger cytotoxic activity on colon cancer HT-29 cell line, over the molybdenocene dichloride (Cp2MoCl2). In contrast, Cp2Mo((2S)-2-amino-3-methyl-3-thiolato-butanoato) exhibited proliferative properties on this cell line. Ubiquitin (Ub)-molybdenocene interactions were investigated using cyclic voltammetry, fluorescence quenching spectroscopy, circular dichroism (CD) and molecular modeling. The thermodynamic parameters (ΔH and ΔS) obtained using fluorescence quenching spectra and van't Hoff plot indicate the Ub-molybdenocene interactions are mainly hydrophobic. The CD data also support hydrophobic interactions with conformational changes in the Ub protein. Docking studies using molecular modeling revealed the amino acids involved in the Ub-molybdenocene interactions and corroborated the hydrophobic nature of the binding combined with hydrogen bonding.

Acute treatment of trigeminal neuralgia with onabotulinum toxin A.

A double-blind, randomized, placebo-controlled study of patients with essential trigeminal neuralgia and treatment with a single injection of onabotulinum toxin A (BTX) was carried out. The efficacy, safety, and tolerability of either 1 mL 0.9% saline plus 50 U of BTX or only 1 mL of 0.9% saline injected subcutaneously in the affected area were evaluated. Cases with involvement of the third branch of the trigeminal nerve also received intramuscularly either 10 U of BTX or matching placebo in the masseter muscle, ipsilateral to the pain location. Pain was assessed with the visual analog scale (VAS). Twenty subjects were administered BTX, and 16 subjects received placebo. Two months after the intervention, a trend to statistical significance was observed for the VAS mean values in subjects treated with BTX and those who received placebo (VAS 4.9 vs 6.63, t test, P = 0.07). Three months after the injection, significant differences were observed in the average VAS score for subjects treated with BTX and those treated with placebo (VAS 4.75 vs 6.94, respectively; t test, P = 0.01). Onabotulinum toxin A was well tolerated and seems to be a safe and useful therapy for patients with essential trigeminal neuralgia.

A study of prevention and regression of cardiac hypertrophy with a prolactin inhibitor in a biological model of ventricular hypertrophy caused by aorto caval fistulae in rat.

BACKGROUND: The possibility of decreasing or reverting left ventricular hypertrophy and, therefore, cardiac hypertrophy (CH) is an important medical issue. The aim of the present study was to evaluate these two possibilities with a 3-week daily dose of captopril, losartan, or bromocriptine in a preventive or corrective model. METHODS: After aorto caval fistulae (ACF) surgery on adult male Wistar rats to induce CH, animals were assigned to the preventive protocol (drug treatment began immediately after surgery) or corrective protocol (hypertrophy was allowed to develop before drug treatment). After treatments, isoproterenol was administered to half of the animals to further induce CH. The groups included the passive control, the sham-operated animals, those with ACF surgery but without drug treatment, and the 3-week treatments with captopril, losartan, or the low or high dose of bromocriptine. RESULTS: Three treatments, with captopril, losartan, or the high dose of bromocriptine, significantly impeded/reverted an increase in CH-related parameters in the preventive/corrective model compared to the surgically treated group without drug treatment. The same effect was found after isoproterenol administration. The present results show an avoidance/reversion of CH with these three treatments. Better results were found with the angiotensin converting enzyme inhibitor (captopril) than with the prolactin inhibitor (bromocriptine). CONCLUSIONS: Treatments with captopril, losartan, and the high dose of bromocriptine were effective in preventing/reversing the manifestation of CH in the preventive/corrective rat models. Further studies are needed to identify the initial mediator, the key component, and the molecular events involved in the pathogenesis of CH.