The progress and challenges in modeling colorectal cancer and the impact on novel drug discovery.

INTRODUCTION: Colorectal cancer (CRC) remains one of the leading causes of cancer-related morbidity and mortality worldwide. This disease is complex and heterogeneous, influenced by a variety of genetic, epigenetic, and environmental factors that drive CRC initiation and progression. Despite advances in therapeutic strategies, the five-year survival rate for metastatic CRC is alarmingly low. Traditional two-dimensional (2D) cell culture systems have been the foundation of cancer research, but their inability to replicate the complex tumor microenvironment (TME) limits their effectiveness. AREAS COVERED: This paper explores the evolution of CRC models, starting with the limitations of traditional 2D cell culture systems and the significant advancements offered by 3D models. Additionally, it highlights 3D bioprinting and on-chip CRC models, which have enhanced the ability to mimic in vivo conditions. EXPERT OPINION: The transition to advanced 3D models represents a pivotal shift in CRC research, offering considerable improvements over the established 2D models. These models hold promise for the development of patient-specific models that better mimic in vivo conditions. However, the inherent complexity of CRC continues to pose challenges in developing models that can fully capture the disease's multifaceted nature. This complexity and high costs associated with these technologies, along with the need for standardized protocols, pose significant challenges to their widespread adoption.

Freeze-drying cycle optimization of an amorphous solid dispersion of resveratrol.

Resveratrol (RES) has demonstrated advantages as anti-cancer, anti-inflammatory, blood sugar-lowering agent and as cardioprotective agent, among others. Despite RES therapeutic advantages its use in pharmaceutical applications is limited by its low oral bioavailability, mainly due to its poor water solubility. Formulation of poorly water-soluble compound as solid dispersion (SD) converts a crystalline into a more soluble in water amorphous drug. Lyophilization or freeze-drying is a process in which water, an organic solvent, or a co-solvent system is frozen, followed by its removal from the sample, initially by sublimation (primary drying) and then by desorption (secondary drying). This study aimed the development and optimization of a bulk freeze-drying cycle by critical process parameters assessment in each phase to prepare a RES third-generation SD, containing Eudragit E PO as hydrophilic polymer at 1:2 ratio, and Gelucire 44/14 as surfactant at 16 % (w/w) to RES, using a tert-butanol (TBA)/Acetate buffer pH 4.5 (75:25) co-solvent system. A RES third-generation SD with good appearance, not cracked, collapsed, or melted was prepared by an optimized and robust bulk lyophilization process. A physicochemical characterization confirmed the conversion of RES to the amorphous state in the SD and formulation stability after 1 month at 40 °C/75 % RH. Increased solubility and higher dissolution rate compared with pure RES were also obtained.

Profiles of interferon-stimulated genes in multiple tissues and circulating pregnancy-associated glycoproteins and their association with pregnancy loss in dairy cows†.

Pregnancy loss (PL) in lactating dairy cows disrupts reproductive and productive efficiency. We evaluated the expression of interferon-stimulated genes (ISG) in blood leukocytes, vaginal and cervical epithelial cells, luteolysis-related genes, progesterone, and pregnancy-associated glycoprotein (PAG) profiles in lactating dairy cows (n = 86) to gain insight about PL. Expression of ISG on d17, d19, and d21 was greater in cows that maintained the pregnancy (P33) compared to nonpregnant with no PL (NP). Greater ISG differences between groups were observed in the cervix (96.7-fold) than vagina (31.0-fold), and least in blood leukocytes (5.6-fold). Based on individual profiles of ISG and PAG, PL was determined to occur either before (~13%) or after (~25%) d22. For cows with PL before d22, ISG expression was similar on d17 but by d21 was lower and OXTR was greater than P33 cows and similar to NP; timing of luteolysis was similar compared to NP cows suggesting embryonic failure to promote luteal maintenance and to attach to the endometrium (no increase in PAG). For cows with PL after d22, ISG expression was similar to P33 cows on d17, d19, and d21 and luteolysis, when it occurred, was later than NP cows; delayed increase in PAG suggested later or inadequate embryonic attachment. In conclusion, PL before d22 occurred due to embryonic demise/failure to signal for luteal maintenance, as reflected in reduced ISG expression by d21. Alternatively, embryos with PL between d22 and 33 adequately signaled for luteal maintenance (ISG) but had delayed/inadequate embryonic attachment and/or inappropriate luteolysis causing PL.

The antidepressant fluoxetine (Prozac®) modulates serotonin signaling to alter maternal peripartum calcium homeostasis.

Antidepressant use is two-fold greater in women compared to men; however, most studies have been performed in male subjects. We aimed to understand the impact of selective serotonin reuptake inhibitors (SSRI, most used antidepressants) on calcium homeostasis and steroid metabolism during the peripartum period. Pregnant sheep (n = 10/group) were treated with vehicle or fluoxetine (most common SSRI) during the last month of gestation. Fluoxetine treatment decreased circulating calcium prior to parturition (8.7 ± 0.1 mg/dL vs 8.2 ± 0.1 mg/dL; P = 0.07). In the control group, total calcium decreased after parturition corresponding to the onset of lactogenesis followed by increase in calcium by day 2 postpartum. Interestingly, this normal transient decrease in circulating calcium was absent in fluoxetine-treated ewes. The steroids cortisol and progesterone were not altered by fluoxetine treatment whereas estradiol was decreased after the onset of treatment (12.4 ± 1.3 vs 9.1 ± 1.2 pg/mL, P = 0.05) and prior to parturition (38.1 ± 8.1 vs 22.3 ± 4.2 pg/mL, P = 0.03). Our hypothesis was supported that fluoxetine treatment alters circulating concentrations of calcium in the peripartum period; however, we surprisingly observed a decrease in estradiol concentrations contrary to reports in in vitro studies.

Comparison of Laparoscopy and Laparotomy in the Management of Early-stage Ovarian Cancer.

Objectives: The objective of this study was to assess the feasibility of minimally invasive surgery for early-stage ovarian cancer (EOC) by comparing the surgical and survival outcomes between laparoscopy and laparotomy. Materials and Methods: This was a retrospective, single-center observational study that included all patients who underwent surgical staging for EOC by laparoscopy or laparotomy between 2010 and 2019. Results: Forty-nine patients were included; of which 20 underwent laparoscopy, 26 laparotomy, and three conversion from laparoscopy to laparotomy. No significant differences were observed between the two groups regarding operative time, number of lymph nodes dissected, or intraoperative tumor rupture rate, while estimated blood loss and transfusion requirements were lower in the laparoscopy group. The complication rate tended to be higher in the laparotomy group. Patients in the laparoscopy group had a faster recovery, with earlier urinary catheter and abdominal drain removal, shorter hospital stay, and a trend toward earlier tolerance of oral diet and mobilization. At a mean follow-up of 45.7 months, 14 patients had disease recurrence, with no differences in the mean progression-free survival between the two groups (36 months for laparoscopy vs. 35.5 months for laparotomy, P = 0.22). Conclusion: Laparoscopic surgery performed by a trained gynecological oncologist is a safe and effective surgical approach for comprehensive staging of EOC, with the additional benefits of a faster recovery compared to laparotomy.

Dopamine receptors D1 and D2 show prognostic significance and potential therapeutic applications for endometrial cancer patients.

OBJECTIVE: Catecholaminergic signaling has been a target for therapy in different type of cancers. In this work, we characterized the ADRß2, DRD1 and DRD2 expression in healthy tissue and endometrial tumors to evaluate their prognostic significance in endometrial cancer (EC), unraveling their possible application as an antitumor therapy. METHODS: 109 EC patients were included. The expression of the ADRß2, DRD1 and DRD2 proteins was evaluated by immunohistochemistry and univariate and multivariate analysis to assess their association with clinic-pathological and outcome variables. Finally, HEC1A and AN3CA EC cell lines were exposed to different concentrations of selective dopaminergic agents alone or in combination to study their effects on cellular viability. RESULTS: ADRß2 protein expression was not associated with clinico-pathological parameters or prognosis. DRD1 protein expression was reduced in tumors samples but showed a significant inverse association with tumor size and stage. DRD2 protein expression was significantly associated with non-endometrioid EC, high grade tumors, tumor size, worse disease-free survival (HR = 3.47 (95%CI:1.35-8.88)) and overall survival (HR = 2.98 (95%CI:1.40-6.34)). The DRD1 agonist fenoldopam showed a reduction of cellular viability in HEC1A and AN3CA cells. The exposure to domperidone, a DRD2 antagonist, significantly reduced cell viability compared to the control. Finally, DRD1 agonism and DRD2 antagonism combination induced a significant reduction in cell viability of the AN3CA cells compared to monotherapy, close to being an additive response than a synergistic effect (CI of 1.1 at 0.5% Fa). CONCLUSION: DRD1 and DRD2 expression levels showed a significant association with clinico-pathological parameters. Both the combined activation of DRD1 and blockage of DRD2 may form an innovative strategy to inhibit tumor growth in EC.

Systematic Review of the Clinical and Experimental Research Assessing the Effects of Craniosynostosis on the Brain.

Although neurocognitive impairment has been considered as the main argument for the surgical treatment of craniosynostosis (CS), recent studies reported subtle deficits in neurological function even in operated patients. However, the cause of these deficits remains poorly understood. This systematic review sought to examine the impact of CS on the brain microstructure, mainly on functional connectivity, and comprehensively summarize the clinical and experimental research available on this topic. A systematic review was performed considering the publications of the last 20 years in PubMed and Web of Science, including relevant human and animal studies of the types of brain-microstructure disturbances in CS. Among the 560 papers identified, 11 were selected for analysis. Seven of those were conducted in humans and 4 in animal models. Resting-state functional magnetic resonance imaging, task-based magnetic resonance imaging, and diffusion tensor imaging were the main instruments used to investigate brain connectivity in humans. The main findings were increased connectivity of the posterior segment of cingulum gyri, reduced interconnectivity of the frontal lobes, and reduced diffusivity on diffusion tensor imaging, which were associated with hyperactivity behaviors and poorer performance on neurocognitive tests. Conversely, despite the lack of evidence of brain dysfunction in animal studies, they reported a tendency toward the development of hyperactive behaviors and impairment of neurocognitive function. Skull restriction caused by CS apparently chronically increases the intracranial pressure and produces white matter injuries. The current evidence supports the contention that an early surgical approach could minimize brain-connectivity impairment in this context.

Surgical treatment in older patients with endometrial cancer: A retrospective study.

INTRODUCTION: Older patients (OP) diagnosed with endometrial cancer (EC) are less likely to receive an optimal surgical treatment compared with non-older patients (NOP). This undertreatment along with the presence of more aggressive tumours at diagnosis can explain the worse prognosis of EC in OP. There is limited evidence comparing perioperative outcomes between OP and NOP, and the benefit of applying complex procedures to OP is still controversial. The primary objective of the study was to compare intraoperative and postoperative complications between NOP and OP with EC that underwent primary surgery. Secondary objectives were to compare surgical management and survival rates. METHODS: This is a retrospective single-centre observational study including women undergoing surgery for EC between 2010 and 2019. Patients were classified according to age as NOP (younger than 75 years) or OP (75 years or older). Basal characteristics and surgical outcomes of groups were compared using Chi-square, Fisher's exact tests, student T-tests or Mann Whitney tests. Kaplan Meier analysis was used to evaluate survival. RESULTS: In total 281 patients underwent primary surgery for EC between 2010 and 2019 in our centre. At diagnosis, 184 patients were younger than 75 years while 97 were 75 and older. No differences were found in disease characteristics. Most of our patients (83,3%) underwent laparoscopic surgery. Pelvic (58,2% vs. 37,1%, p = 0,001) and para-aortic (46,7% vs. 23,7%, p < 0,001) lymphadenectomies were performed more frequently in NOP compared with OP. Rates of intra-operative (6,5% vs. 12,4%, p = 0,116) and post-operative (13,0% vs. 20,6%, p = 0,120) complications were not statistically different between NOP and OP, and neither was the rate of severe complications according to Clavien-Dindo classification (5,4% vs. 8,2% of complications grade III-V respectively, p = 0,387). The 5-year disease-specific survival (DSS) rate tended to be lower in the OP than in the NOP (74,8% vs. 82,5%, p = 0,071). Considering only patients in whom complete surgical staging was performed, OP presented similar DSS to NOP, with comparable complication rate. CONCLUSIONS: OP do not present a significantly higher rate of perioperative complications compared to NOP. However, they underwent fewer lymphadenectomies and tended to present poorer DSS. Further studies are needed to standardize the surgical management of these patients.

Effect of drying methods on nutritional constitutes of fermented grape residue.

One of the biggest hurdles faced by the wine industry is the disposal of residual biomass generated after vinification. Although this residue is biodegradable, it constitutes a potential source of environmental pollutants. To alleviate this issue, this biomass may be used in alternative applications; for example, it may be transformed into an enriched flour that can be used to improve the nutrient content in different foods. In this study, were evaluated the effects of drying processes on the relevant nutritional components in dry extracts obtained from the residue of fermented grape pomace. The concentrations of phenolic compounds and anthocyanins were higher when drying the flour by the traditional oven procedure than by freeze-drying. The highest difference (approximately 40%) was observed for tannin compounds. Therefore, drying in an oven is recommended due to the lower loss of bioactive compounds, in addition to being simple and cheap.

Functionalized FcRn-targeted nanosystems for oral drug delivery: A new approach to colorectal cancer treatment.

Colorectal cancer (CRC) is the second type of cancer with the highest lethality rate. The current chemotherapy to treat CRC causes systemic toxicity, unsatisfying response rate, and low tumor-specific selectivity, which is mainly administered by invasive routes. The chronic and aggressive nature of cancers may require long-term regimens. Thus, the oral route is preferred. However, the orally administered drugs still need to surpass the harsh environment of the gastrointestinal tract and the biological barriers. Nanotechnology is a promising strategy to overcome the oral route limitations. Targeted nanoparticle systems decorated with functional groups can enhance the delivery of anticancer agents to tumor sites. It is described in the literature that the neonatal Fc receptor (FcRn) is expressed in cancer tissue and overexpressed in CRC epithelial cells. However, the impact of FcRn-targeted nanosystems in the treatment of CRC has been poorly investigated. This review article discusses the current knowledge on the involvement of the FcRn in CRC, as well as to critically assess its relevance as a target for further localization of oral nanocarriers in CRC tumor cells. Finally, a brief overview of cancer therapeutics, strategies to design the nanoparticles of anticancer drugs and a review of decorated nanoparticles with FcRn moieties are explored.

Sweet's Syndrome: A Case Report of a Rare Extraintestinal Manifestation of Ulcerative Colitis.

Sweet's syndrome is a neutrophilic dermatosis of unknown etiology and a rare extraintestinal manifestation of ulcerative colitis. Classically, it is more common in women with active inflammatory bowel disease (IBD). This syndrome typically presents in patients with acute-onset painful tender erythematous skin lesions and is usually accompanied by fever, arthralgia, and elevated inflammatory markers. Histological examination is characterized by diffuse dense dermal neutrophilic infiltrate with leukocytoclasia, without vasculitis. The treatment goals are to reduce morbidity and complications, and the most effective therapy is systemic corticosteroids. Early recognition of this syndrome is essential to improve our diagnostic and therapeutic abilities. We report a case of a 59-year-old female with ulcerative colitis, which presented with manifestations of Sweet's syndrome.

Risk Factors for the Incidence of Dental Caries in Low, Very Low, and Extremely Low Birth Weight Children: A Cohort Study

Abstract Objective: To assess the incidence of caries in a two-year period among low birth weight (LBW), very low birth weight (VLBW), and extremely low birth weight (ELBW) children considering socioeconomic indicators, dietary factors and oral hygiene. Material and Methods: A convenience sample was formed of 42 low birth weight children aged two to five years at baseline. Two examiners diagnosed caries using the World Health Organization criteria. Birth weight, socioeconomic indicators and diet were collected from medical records and questionnaires. Binomial models were used to estimate unadjusted and adjusted rate ratios (RR) and respective 95% confidence intervals for the factors evaluated. Results: Thirty-six children were re-examined after two years. The incidence of dental caries was 36.7%. The dmft index was 0.44 (±1.25) at baseline and increased to 1.36 (±3.85) at follow-up. VLBW children (1,000 to 1,500 g) (RR=0.23; 95%CI: 0.08-0.72) and LBW children (1,500 to 2,500 g) (RR=0.06; 0.01-0.55) had fewer carious lesions compared to ELBW children (<1,000 g). Carious lesions were more frequent among children with a lower income (RR=6.05; 1.05-34.84) and less frequent among those who did not consume sweetened juice, tea or yogurt (RR: 0.21; 0.07-0.62). Conclusion: An inverse dose-response relation was found between birth weight and the incidence of caries. A lower income and the consumption of sweetened beverages were risk factors for the development of caries (AU).

Criptococosis sistémica con presentación cutánea / Systemic cryptococcosis with cutaneous presentation

La enfermedad avanzada por VIH sigue siendo un reto importante. A pesar de grandes avances en la última década de la terapia antirretroviral (TAR), muchos pacientes mueren a causa de enfermedades oportunistas relacionadas con el VIH. La criptococosis es una infección micótica oportunista causada por especies de Cryptococcus. Desde el punto de vista clínico y epidemiológico, la criptococosis se asocia con las condiciones de inmunosupresión celulares y es causada principalmente por Cryptococcus neoformans (serotipo D) y Cryptococcus grubii (serotipo A). En los últimos años, el aumento de número de casos de síndrome de inmunodeficiencia adquirida (SIDA), ha conllevado a un aumento de la incidencia de criptococosis. La infección normalmente se produce por inhalación del agente causal. Presentamos un caso de infección diseminada con Cryptococcus neoformans, con una exuberante presentación cutánea tras el inicio de la terapia antirretroviral (TAR), con una buena evolución clínica. (AU)

Rhabdomyolysis Due to Salmonellosis: A Case Report of a Rare Presentation.

Salmonella infection has been commonly associated with gastrointestinal symptoms, such as diarrhea, abdominal pain, and nausea. However, in some cases, patients can develop rare and life-threatening complications such as rhabdomyolysis. Here, we report a case of gastroenteritis due to Salmonella enteritidis infection complicated by rhabdomyolysis. The patient was successfully treated with fluids and antibiotics. Despite rare, the association of Salmonella infection and rhabdomyolysis may occur. Prompt diagnosis and treatment with aggressive fluid replacement and antibiotics are paramount to prevent acute kidney injury.

Synthesis of a chitosan nanoparticle suspension and its protective effects against enamel demineralization after an in vitro cariogenic challenge.

OBJECTIVE: Our study aims to synthesize, characterize, and determine the effects of a ChNPs suspension on human enamel after cariogenic challenge via pH-cycling. METHODOLOGY: ChNPs were synthesized by ion gelation and characterized by Transmission Electron Microscopy (TEM) and Dynamic Light Scattering. Forty enamel blocks were divided into four groups (n=10/group): (i) ChNPs suspension; (ii) chitosan solution; (iii) 0.05% sodium fluoride (NaF) solution; and (iv) distilled water. Specimens were exposed to cariogenic challenge by cycling in demineralization solution (3 h) and then remineralized (21h) for 7 days. Before each demineralization cycle, the corresponding solutions were passively applied for 90 s. After 7 days, specimens were examined for surface roughness (Ra) and Knoop hardness (KHN) before and after the cariogenic challenge; % KHN change (variation between initial and final hardness), and surface topography by an optical profilometer. The data were analyzed by repeated-measures ANOVA, One-way ANOVA, and Tukey tests (α=0.05). RESULTS: TEM images showed small spherical particles with diameter and zeta potential values of 79.3 nm and +47.9 mV, respectively. After the challenge, all groups showed an increase in Ra and a decrease in KHN values. Optical profilometry indicated that ChNPs- and NaF-treated specimens showed uneven roughness interspersed with smooth areas and the lowest %KHN values. CONCLUSION: The ChNPs suspension was successfully synthesized and minimized human enamel demineralization after a cariogenic challenge, showing an interesting potential for use as an oral formulation for caries prevention.

Idiopathic Chronic Eosinophilic Pneumonia.

Idiopathic chronic eosinophilic pneumonia (CEP) is a rare disease of unknown cause characterized by eosinophilic alveolar and interstitial infiltration. The authors describe the case of a 46-year-old black man, presenting with insidious onset and progressive course of dyspnea on minimum exertion, cough, fever, night sweats, and weight loss for one year and worsening in the last three months. The main findings were serum eosinophilia. Chest radiographs showed multifocal infiltrations of irregular distribution in both lungs and a restrictive functional impairment. The patient underwent open lung biopsy, and the anatomopathological examination revealed consolidation by exudate constituted predominantly by macrophages (25%) and eosinophils (51%), which filled small air spaces, including respiratory and membranous bronchioles. The anatomopathological diagnosis was eosinophilic pneumonia (eosinophils > 25% is widely accepted for diagnosing eosinophilic pneumonia). The patient had a good clinical response after starting corticosteroid therapy.

Developmental Enamel Defects and Dental Caries in the Primary Dentition of Preterm Children.

Purpose: To assess developmental enamel defects (DED) and dental caries of preterm (PT) and/or low birth weight (LBW) children compared to full term (FT) and/or normal birth weight (NBW) infants, and to evaluate the association of DED with socioeconomic factors, gestational health, and postnatal factors.
Methods: This study included 84 two- to five-year-old children. The PT/LBW group included 42 children who received medical care at a university hospital, while FT/ NBW group included 42 subjects. Children were matched by sex and age (1:1 ratio). Descriptive statistics, bivariate analysis, and Poisson regression were used to analyse the data.
Results: Children in the PT/LBW group had a significantly higher number of teeth with DED than subjects in the FT/NBW group. No difference was observed between the groups regarding dental caries (P >0.05). Admission to the neonatal intensive care was significantly associated with DED unit (prevalence ratio = 0.21 [95 percent confidence interval = 0.1 to 0.5]).
Conclusion: PT/LBW children presented more DED than FT/NBW children. No differences were observed between the groups for dental caries. Admission to the neonatal intensive care unit was associated with DED.

Synthesis of a chitosan nanoparticle suspension and its protective effects against enamel demineralization after an in vitro cariogenic challenge

Abstract Objective Our study aims to synthesize, characterize, and determine the effects of a ChNPs suspension on human enamel after cariogenic challenge via pH-cycling. Methodology ChNPs were synthesized by ion gelation and characterized by Transmission Electron Microscopy (TEM) and Dynamic Light Scattering. Forty enamel blocks were divided into four groups (n=10/group): (i) ChNPs suspension; (ii) chitosan solution; (iii) 0.05% sodium fluoride (NaF) solution; and (iv) distilled water. Specimens were exposed to cariogenic challenge by cycling in demineralization solution (3 h) and then remineralized (21h) for 7 days. Before each demineralization cycle, the corresponding solutions were passively applied for 90 s. After 7 days, specimens were examined for surface roughness (Ra) and Knoop hardness (KHN) before and after the cariogenic challenge; % KHN change (variation between initial and final hardness), and surface topography by an optical profilometer. The data were analyzed by repeated-measures ANOVA, One-way ANOVA, and Tukey tests (α=0.05). Results TEM images showed small spherical particles with diameter and zeta potential values of 79.3 nm and +47.9 mV, respectively. After the challenge, all groups showed an increase in Ra and a decrease in KHN values. Optical profilometry indicated that ChNPs- and NaF-treated specimens showed uneven roughness interspersed with smooth areas and the lowest %KHN values. Conclusion The ChNPs suspension was successfully synthesized and minimized human enamel demineralization after a cariogenic challenge, showing an interesting potential for use as an oral formulation for caries prevention.

Uterine secretory activity and histology of prepubertal female dogs in an animal model of partial ablation of endometrial glands development / Atividade secretória uterina e histologia de cadelas pré-púberes em um modelo animal de ablação parcial do desenvolvimento das glândulas uterinas

Inadequate exposure of the female reproductive system to steroids in uterine developmental periods can partially inhibit the development of endometrial glands in dogs. However, the effects of steroids on the formed glands functionality remain unknown, as well as the possible occurrence of endometrial fibrosis. This study aimed to evaluate the secretory activity of endometrial glands in prebubertal female dogs submitted to a protocol of partial ablation of the uterine adenogenesis. Sixteen females of non-specific breed were distributed into two groups; MPA (n=8), females that received applications of medroxyprogesterone acetate every 3 weeks; and C (n=8) untreated control females. Ovariohysterectomy was performed in all animals at the age of 6 months and evaluated the uterine horns by histological and histochemistry exams. The secretion intensity (degrees 1-4) was evaluated using periodic acid-Schiff (PAS) and alcian blue (AB) pH 2.5. Histological evaluation was performed using Masson's trichrome and toluidine blue. Only degree 1 and 2 marks for PAS were observed in both groups, with no difference of uterine secretion intensity between the groups regarding the degrees found. However, the MPA group revealed higher intensity of uterine secretion compared to group C (p<0.05). Staining with AB pH 2.5 also revealed only degree 1 and 2 marks in both groups, with no statistically significance between them. Masson's trichrome staining revealed no marks in the periglandular region in both groups. A higher among of mast cells was observed in the myometrial region of the uterus in both groups. Prepubertal female dogs with partial ablation of the uterine adenogenesis present minimal uterine secretory activity, absence of periglandular fibrosis and increased presence of mast cells in the myometrium compared to endometrium.(AU)

A exposição inadequada do sistema reprodutor feminino a esteróides em períodos do desenvolvimento uterino pode inibir parcialmente o desenvolvimento das glândulas endometriais em cães. Entretanto, não se conhece os efeitos dos esteróides sobre a funcionalidade das glândulas formadas, bem como a possível ocorrência de fibrose endometrial. Objetivou-se avaliar a atividade secretória das glândulas endometriais de cadelas pré-púberes submetidas a protocolo de ablação parcial da adenogênese uterina. Foram utilizadas 16 fêmeas, sem-raça-definida, distribuídas nos grupos MPA (n=8), fêmeas que receberam aplicações de acetato de medroxiprogesterona a cada 3 semanas, e C (n=8), fêmeas controle não tratadas. Aos seis meses de idade, foi realizada ovariohisterectomia em todos os animais, e avaliados os cornos uterinos pelo exame histológico e de histoquímica. Para avaliar a intensidade de secreção (graus 1-4), foram utilizadas periodic acid-Schiff e alcian blue (AB) pH 2,5. Para a avaliação histológica foram utilizados tricrômico de Masson e azul de toluidina. Apenas marcações graus 1 e 2 foram observadas para PAS em ambos os grupos, sem diferença na intensidade de secreção uterina entre grupos com relação aos graus encontrados. Entretanto, o grupo MPA apresentou maior intensidade de secreção uterina em relação ao grupo C (p<0,05). Com relação ao AB pH 2,5, em ambos os grupos também foram encontradas apenas marcações de graus 1 e 2, sem diferença estatística entre grupos. Não foram observadas marcações para a coloração de tricrômico de Masson na região periglandular, em ambos os grupos. Foi observada maior quantidade de mastócitos presentes no útero na região do miométrio, em ambos os grupos. Conclui-se que cadelas pré-púberes com ablação parcial da adenogênese uterina apresentam mínima atividade secretória uterina, ausência de fibrose periglandular e maior presença de mastócitos no miométrio em relação ao endométrio.(AU)

Synthesis and characterization of TPP/chitosan nanoparticles: Colloidal mechanism of reaction and antifungal effect on C. albicans biofilm formation.

In the present study chitosan (Chit) nanoparticles were synthetized by the ionic gelation process, using tripolyphosphate (TPP) as crosslinking agent. The TPP/Chit nanoparticle formation was evaluated by titrations, measuring electrical conductivity (k), zeta potential (ZP), hydrodynamic diameter (Dh), viscosity (η) and heat by isothermal calorimetry (ITC). The antifungal effects were evaluated by C. albicans time-kill assays, inhibition of C. albicans initial adhesion and biofilm formation in comparison with nystatin and chitosan. Conductometric titration exhibited a typical precipitation profile, with an inflection at molar ratio of [TPP]/[Chitmon] ≈ 0.3, suggesting a 1:3.3 stoichiometry. The highest Dh, ZP and η values were shown at the beginning of titrations, due to the intramolecular repulsion between Chit-Chit. With addition of TPP, the values showed gradual reduction, with an intermediary transition at [TPP]/[Chitmon] ≈ 0.16, which was attributed to the partial breakdown of interchain crosslinking and formation of discrete charged aggregates. After this point, reaction should occur by neutralization of these assemblies, causing new reduction in values of Dh, ZP and η until [TPP]/[Chitmon] ≈ 0.3, when they reached their lowest values. ITC experiment also showed the occurrence of two bindings (K1 = 3.6 × 103 and K2 = 7.7 × 104), which were entropy driven. Biological results showed lower C. albicans viability for TPP/Chit over 24 h compared with chitosan and nystatin at MIC and 2 MIC. Moreover, TPP/Chit showed 25-50% inhibition of C. albicans adhesion and biofilm formation. The results showed that TPP/Chit nanoparticles reduced the initial adhesion and biofilm formation of C. albicans and demonstrated potential for use in a formulation for the treatment of oral candidiasis.