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1.
Chemistry ; 2020 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-32030819

RESUMO

Nitridophosphates exhibit an intriguing structural diversity with different structural motifs, e.g. chains, layers or frameworks. In this contribution we present the novel nitridophosphate Sr 3 P 3 N 7 with unprecedented dreier double chains. Crystalline powders were synthesized using the ammonothermal method, while single crystals were obtained by high-pressure multianvil technique. The crystal structure of Sr 3 P 3 N 7 was solved and refined from single-crystal X-ray diffraction and confirmed by powder X-ray methods. Sr 3 P 3 N 7 crystallizes in monoclinic space group P 2/ c . Energy dispersive X-ray and Fourier transformed infrared spectroscopy were conducted to confirm the chemical composition as well as the absence of NH x functionality. The optical band gap was estimated to be 4.4 eV using diffuse reflectance UV-Vis spectroscopy. Upon doping with Eu 2+ , Sr 3 P 3 N 7 shows a broad deep-red to infrared emission (λ em = 681 nm, fwhm ≈ 3402 cm -1 ) with an internal quantum efficiency of 42%.

3.
Chemistry ; 2020 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-31944443

RESUMO

Barium imidonitridophosphate BaP6N10NH was synthesized at 5 GPa and 1000 °C with a high-pressure high-temperature approach using the multianvil technique. Ba(N3)2, P3N5 and NH4Cl were used as starting materials, applying a combination of azide and mineralizer routes. The structure elucidation of BaP6N10NH (P63, a = 7.5633(11), c = 8.512(2) Å, Z = 2) was performed by a combination of transmission electron microscopy and single-crystal diffraction with microfocused synchrotron radiation. Phase purity was verified by Rietveld refinement. 1H and 31P solid-state NMR and FTIR spectroscopy are consistent with the structure model. The chemical composition was confirmed by energy-dispersive X-ray spectroscopy and CHNS analyses. Eu2+-doped samples of BaP6N10NH show blue emission upon excitation with UV to blue light (λem = 460 nm, fwhm = 2423 cm-1) representing unprecedented Eu2+-luminescence of an imidonitride.

4.
Quintessence Int ; 51(2): 170-177, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31942577

RESUMO

OBJECTIVE: Some patients with Down syndrome experience premature edentulism, which can lead to severe alveolar atrophy. This may cause retention problems with purely mucosa-supported dentures and ill-fitting total dentures. The intellectual disability associated with Down syndrome, with an (implied) inadequate ability for compliance, may pose a further challenge to dental treatment. The aim of this case report was to demonstrate that a combined implant-prosthetic denture with bar constructions can, nevertheless, be implemented in elderly Down syndrome patients with limited cooperation ability. METHOD AND MATERIALS: This report is the first to describe the procedure for an implant-supported total prosthetic restoration with bar joint in a 52-year-old edentulous patient with Down syndrome and limited ability to cooperate. Previous dental solutions had severely curtailed the patient's quality of life. By combining various forms of treatment, including behavior management, the course of therapy could be adapted to the patient's cooperation capability. RESULTS: The implant-supported total prosthetic restoration with bar joint was well accepted by the patient. Moreover, the patient's relatives reported that his life quality had improved distinctly (eg, considerable weight-gain, more positive mood). No impairments of the prostheses were observed during the 24-month follow-up period, and both implants remained clinically inconspicuous. CONCLUSION: The lack, or inadequacy, of dental prostheses can impair the life quality of individuals in need of such restorations. Implant-supported dentures in combination with a bar construction improve the retention of prostheses in atrophied jaws. This form of restoration is also proving to be a successful therapy option for elderly persons with Down syndrome.


Assuntos
Implantes Dentários , Síndrome de Down , Arcada Edêntula , Idoso , Prótese Dentária Fixada por Implante , Falha de Restauração Dentária , Revestimento de Dentadura , Seguimentos , Humanos , Pessoa de Meia-Idade , Qualidade de Vida , Resultado do Tratamento
5.
Med Sci Sports Exerc ; 2019 Dec 23.
Artigo em Inglês | MEDLINE | ID: mdl-31876668

RESUMO

INTRODUCTION: Acute mountain sickness (AMS) may develop in non-acclimatized individuals after exposure to altitudes ≥2500m. Anecdotal reports suggest that endurance trained (ET) athletes with a high maximal oxygen uptake (VO2max) may be at increased risk for AMS. Possible underlying mechanisms include a training-induced increase in resting parasympathetic activity, higher resting metabolic rate (RMR), and lower hypoxic ventilatory response (HVR). METHODS: In 38 healthy, non-acclimatized men (19 ET and 19 untrained controls (UT), VO2max 66±6 vs. 45±7 mL/min/kg; p<0.001) peripheral oxygen saturation (SpO2), heart rate variability, RMR, and poikilocapnic HVR were assessed at 424m and during 48 hours at 3450m following passive ascent by train (~2 hours). AMS was evaluated by AMS-C score. RESULTS: On day 1 at altitude, ET presented with a higher AMS incidence (42% vs. 11%; p<0.05) and severity (AMS-C score: ET: 0.48±0.5 vs UT: 0.21±0.2; p=0.03), but no group difference was found on day 2 and 3. SpO2 decreased upon arrival at altitude (ET: 82±6% vs. UT: 83±4%; ptime<0.001) with a significantly different time course between ET and UT (ptime*group=0.045). Parasympathetic activity decreased at altitude (p<0.001) but was always higher in ET (p<0.05). At altitude RMR increased (p<0.001) and was higher in ET (p<0.001). HVR increased only in ET (p<0.05) and was greater than in UT after 24 and 48 hours (p<0.05). CONCLUSION: ET are at higher risk for developing AMS on the first day following passive and rapid ascent to 3450m, possibly due to an increased parasympathetic activity and an increased RMR, while HVR appeared to be of minor importance. Differences in AMS time course and physiological responses should be taken into consideration when ET are planning high-altitude sojourns.

6.
United European Gastroenterol J ; 7(9): 1250-1260, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31700638

RESUMO

Background: Obesity is a risk factor for colorectal cancer (CRC). Objective: The objective of this article is to investigate whether anthropometric measures reflecting visceral obesity are better predictors of CRC than body mass index (BMI). Methods: Data were analysed from the Malmö Diet and Cancer study in Sweden, comprising 16,669 women and 10,805 men (median age 56.6 and 59.1 years) followed for a median 21.5 years. Diagnoses of CRC were identified using Swedish national registers. Cox regression was used to test the associations of BMI, waist circumference (WC), waist-hip ratio, waist-to-height ratio, waist-to-hip-to-height ratio, A Body Shape Index (ABSI) and percentage body fat with the development of CRC adjusted for age, alcohol consumption, smoking, education and physical activity in men and women. Results: None of the measures were significantly associated with an increased risk for CRC in women. WC was the strongest predictor of colon cancer (CC) in men and the only measure that was independent of BMI. ABSI was the only measure significantly associated with the risk of rectal cancer in men. Conclusions: Visceral obesity, best expressed as WC, is a risk factor for CC in men but a poor predictive marker for CRC in women.

7.
Psychopathology ; 52(5): 304-315, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31734668

RESUMO

BACKGROUND: To examine psychopathology present under prolonged antipsychotic treatment in schizophrenia and to analyse their relationship to both the duration of the prodromal stage (DPS; time between onset of first unspecific psychological symptoms and first schizophrenic symptoms) and the duration of untreated psychosis (DUP; time between the onset of psychosis and the initiation of antipsychotic treatment). METHODS: The psychopathology of 93 patients was assessed cross-sectionally using the Scales for the Assessment of Negative and Positive Symptoms and the Brief Psychiatric Rating Scale. DPS and DUP were assessed by means of the patient records and the Interview for the Retrospective Assessment of the Onset and Course of Schizophrenia and Other Psychoses. A path analysis using maximum likelihood estimation was conducted with the program Analysis of Moment Structures for Windows. RESULTS: The resulting path model indicated that DPS was predictive for a more severe negative symptomatology in schizophrenia, whereas DUP was associated with a more severe positive symptomatology in the long-term. Furthermore, DUP showed an inverse correlation with the age of the patients at the onset of both first unspecific psychological symptoms and first schizophrenic symptoms. CONCLUSION: A long prodromal stage suggests an increased risk of a long-term progression with negative symptoms in schizophrenia, whereas a delayed start of antipsychotic treatment could lead to an increased manifestation and severity of positive symptoms in the long term. These results underline the need to shorten the duration of the prodrome by an early detection and adequate intervention in patients with increased risk to develop psychosis.

8.
Gut ; 2019 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-31601615

RESUMO

OBJECTIVE: The ethiopathogenesis of irritable bowel syndrome (IBS) is unknown. While a link to the gut microbiome is postulated, the heterogeneity of the healthy gut makes it difficult to draw definitive conclusions. We aimed to describe the faecal and mucosa-associated microbiome (MAM) and health correlates on a community cohort of healthy and IBS individuals with no colonoscopic findings. DESIGN: The PopCol study recruited a random sample of 3556 adults; 745 underwent colonoscopy. IBS was defined by Rome IV criteria and organic disease excluded. 16S rRNA gene sequencing was conducted on sigmoid biopsy samples from 376 representative individuals (63 IBS cases) and faecal samples from 185 individuals (32 IBS cases). RESULTS: While sigmoid MAM was dominated by Lachnospiraceae, faeces presented a higher relative abundance of Ruminococcaceae. Microbial richness in MAM was linearly correlated to that in faeces from the same individual (R²=0.255, p<3E-11) as was diversity (R²=0.06, p=0.0022). MAM diversity decreased with increasing body mass index (BMI; Pearson's r=-0.1, p=0.08) and poorer self-rated health (r=-0.15, p=0.007), but no other health correlates. Faecal microbiome diversity was correlated to stool consistency (r=-0.16, p=0.043). Several taxonomic groups were correlated to age, BMI, depression and self-reported health, including Coprococcus catus associated with lower levels of depression (r=-0.003, p=0.00017). The degree of heterogeneity observed between IBS patients is higher than that observed between healthy individuals. CONCLUSIONS: No distinct microbial signature was observed in IBS. Individuals presenting with low self-rated health or high BMI have lower gut microbiome richness.

9.
Anticancer Res ; 39(9): 4965-4970, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31519602

RESUMO

BACKGROUND/AIM: Colonic crypts with normal epithelium albeit with corrupted shapes (CCS) were previously found beneath nonpolypoid adenomas (NPA). This study aimed to analyze the distribution of proliferating cells (PC) and p53-up-regulated cells in CCS. MATERIALS AND METHODS: Sections from 48 NPA were immunostained with the proliferating-marker Ki67 and against the tumor-suppressor protein p53. RESULTS: Asymmetric-haphazardly distributed PC were found in 87.5% of the NPA, continuous PC-domains in 8.3%, asymmetric-haphazardly distributed single PC in 4.2% and p53-up-regulated cells in 29.2%. In 12 controls, the normal-shaped crypts revealed symmetrically-distributed PC-domains in their lower thirds, and no p53-up-regulated cells. CONCLUSION: The normal epithelium that lines the CCS below NPA, thrives with relocated PC-domains, and with occasional p53-up-regulated cells. These findings strongly suggest that the normal epithelium of CCS beneath NPA might harbor somatic mutations. The accretion of putative mutated CCS might play an important role in the evolution of nonpolypoid adenomas in the human colon.


Assuntos
Adenoma/genética , Neoplasias do Colo/genética , Regulação Neoplásica da Expressão Gênica , Mucosa Intestinal/metabolismo , Proteína Supressora de Tumor p53/genética , Adenoma/metabolismo , Adenoma/patologia , Proliferação de Células , Neoplasias do Colo/metabolismo , Neoplasias do Colo/patologia , Humanos , Fenótipo , Proteína Supressora de Tumor p53/química , Proteína Supressora de Tumor p53/metabolismo , Regulação para Cima
10.
Sci Rep ; 9(1): 13774, 2019 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-31551531

RESUMO

New Synthetic Opioids (NSOs) are one class of New Psychoactive Substances (NPS) enjoying increasing popularity in Europe. Data on their toxicological or metabolic properties have not yet been published for most of them. In this context, the metabolic fate of three NSOs, namely, trans-3,4-dichloro-N-[2-(dimethylamino)cyclohexyl]-N-methyl-benzenacetamide (U-51754), trans-4-bromo-N-[2-(dimethylamino)cyclohexyl]-N-methyl-benzamide (U-47931E), and 2-methoxy-N-phenyl-N-[1-(2-phenylethyl)piperidin-4-yl] acetamide (methoxyacetylfentanyl), was elucidated by liquid chromatography high-resolution mass spectrometry after pooled human S9 fraction (phS9) incubations and in rat urine after oral administration. The following major reactions were observed: demethylation of the amine moiety for U-51754 and U-47931E, N-hydroxylation of the hexyl ring, and combinations thereof. N-dealkylation, O-demethylation, and hydroxylation at the alkyl part for methoxyacetylfentanyl. Except for U-47931E, parent compounds could only be found in trace amounts in rat urine. Therefore, urinary markers should preferably be metabolites, namely, the N-demethyl-hydroxy and the hydroxy metabolite for U-51754, the N-demethylated metabolite for U-47931E, and the N-dealkylated metabolite as well as the O-demethylated one for methoxyacetylfentanyl. In general, metabolite formation was comparable in vitro and in vivo, but fewer metabolites, particularly those after multiple reaction steps and phase II conjugates, were found in phS9. These results were consistent with those of comparable compounds obtained from human liver microsomes, human hepatocytes, and/or human case studies.

11.
Artigo em Inglês | MEDLINE | ID: mdl-31372757

RESUMO

Postpartum depression (PPD) is a common complication following delivery, though evidence-based treatment options are limited. This study explores the feasibility and efficacy of outpatient PPD treatment with transdermal estradiol (TE). In a pilot, double-blind, placebo-controlled trial, women with PPD were randomized to receive transdermal 17ß-estradiol (100 mcg/day) or placebo patch. Over 6 weeks, women completed weekly ratings on the Beck Depression Inventory (BDI), Edinburgh Postnatal Depression Scale (EPDS), and Hamilton Depression Scale (HAM-D). Primary outcome measures were treatment response (> 50% decrease from baseline BDI) and remission (BDI < 10) at 6 weeks, and secondary outcome measures included severity on all scales at weeks 3 and 6. Of 12 recruited women, 6 received TE and 6 received placebo. By week 6, 5 women receiving TE responded to treatment and 4 showed symptom remission, compared to 2 responders and 1 remitter in the placebo group. This difference was not significant (p = 0.24). In a mixed-model of BDI ratings, TE was associated with a 9.2 point decrease at 3 weeks (95%CI - 19.5 to + 1.0, p = 0.074) and a 10.5 point decrease at 6 weeks (95%CI - 21.0-0.0, p = 0.049) compared to placebo, though these differences did not survive multiple comparisons correction. Analogous effects were found for HAM-D but not EPDS scores. Interestingly, no significant difference in plasma estradiol levels existed between groups. We were unable to demonstrate a significant therapeutic benefit of TE compared with placebo in PPD. Although limited by under-recruitment and loss to follow-up, our results suggest TE is a feasible option for outpatient PPD management, with preliminary evidence (based on secondary outcomes) for efficacy. Therapeutic effects may be seen as early as 3 weeks and may not directly depend on peripheral measures of estradiol.

12.
Scand J Gastroenterol ; 54(9): 1065-1069, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31453726

RESUMO

Background and study aims: Barrett's esophagus is a premalignant condition in the distal esophagus associated with esophageal adenocarcinoma. Since gastroesophageal reflux is known to be of etiological importance in both Barrett's esophagus and esophageal adenocarcinoma, we aimed to study which endoscopic alterations at the Z-line can be attributed to a previous history of reflux symptoms. Patients and methods: From 1988, a population cohort in Sweden has been prospectively studied regarding gastrointestinal symptoms, using a validated questionnaire. In 2012, the population was invited to undergo a gastroscopy and participate in the present study. In order to determine which endoscopic alterations that can be attributed to a previous history of gastroesophageal reflux, three different endoscopic definitions of columnar-lined esophagus (CLE) were used: (1) ZAP I, An irregular Z-line with a suspicion of tongue-like protrusions; (2) ZAP II/III, Distinct, obvious tongues of metaplastic columnar epithelium; (3) CLE ≥1 cm, The Prague C/M-classification with a minimum length of 1 cm. Results: A total of 165 community subjects were included in the study. Of these, 40 had CLE ≥ 1 cm, 99 had ZAP I, and 26 had ZAP II/III. ZAP II/III was associated with an over threefold risk of previous GER symptoms (OR: 3.60, CI: 1.49-8.70). No association was found between gastroesophageal reflux and ZAP I (OR: 2.06, CI: 0.85-5.00), or CLE ≥1 cm (OR: 1.64, CI: 0.77-3.49). Conclusions: In a general community, the only endoscopic alteration to the Z-line definitely linked to longstanding GER symptoms was the presence of obvious tongues of metaplastic columnar epithelium (ZAP II/III).

13.
Artigo em Inglês | MEDLINE | ID: mdl-31464033

RESUMO

AIM: To evaluate the accuracy of the Kejian 8000 (KJ-8000) transcutaneous bilirubinometer in infants of differing ethnicity and gestational age. METHODS: This was a prospective study of infants in the Newborn Care Unit at Gold Coast University Hospital. Transcutaneous bilirubin (TcB) and serum bilirubin (SBR) results were compared using linear regression and a Bland-Altman plot. Predicted indices were calculated to assess the KJ-8000 as a screening tool using local jaundice management guidelines. RESULTS: A total of 416 paired samples were collected from 201 infants. There was a strong correlation between TcB and SBR with a Pearson correlation coefficient of 0.8 (<0.00001). The bias was -5.9 µmol/L (95% confidence interval: -101, 89). The bias was not evenly spread, with the KJ-8000 tending to underestimate at higher SBR levels. Infants <32 weeks' gestation had a poor correlation of 0.48. Non-Caucasian infants were more likely to have TcB overestimation, and measurements were less precise. As a screening tool using local guidelines, the KJ-8000 had a sensitivity, specificity, positive predictive value and negative predictive value of 83, 53, 20 and 96%, respectively, and is predicted to avoid blood tests in 48% of infants screened. CONCLUSIONS: In this study, the correlation and agreement of TcB measurements using the KJ-8000 were not as good as has been reported with other more studied devices but may still have value as a screening tool. The poor correlation in preterm infants suggests that use should be restricted to term infants. The overall results of this study are affected by an underrepresentation of term infants, and so, further clinical assessment of this device should be undertaken before it can be recommended for widespread use.

14.
Anticancer Res ; 39(8): 4259-4263, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31366515

RESUMO

BACKGROUND/AIM: Sessile serrated polyps (SSP) are characterized by crypts with corrupted shapes (CCS). MATERIALS AND METHODS: The number of CCS and the lateral size of 60 non-dysplastic SSP (NDSSP) were investigated. RESULTS: Out of 60 NDSSP, 34 were small (≤9 mm) and 26, large (≥10 mm). In total, 1,101 CCS were recorded: 547 CCS were connected to the lumen (CCSL) and 554 CCS were not (CCSNL). The lateral size of NDSSP, the total number of CCS and the number of CCSNL were significantly higher in large NDSSP than in small NDSSP. Conversely, the number of CCS connected to the lumen/mm (CCSL/mm) and of crypts with normal shapes connected to the lumen/mm (CCSNL/mm), were significantly lower in large NDSSP than in small NDSSP. CONCLUSION: The lateral expansion of large NDSSP ensues via increased numbers of CCS at the expense of a decreased number of both CCSL/mm and CCSNL/mm.


Assuntos
Adenoma/fisiopatologia , Neoplasias do Colo/fisiopatologia , Pólipos do Colo/fisiopatologia , Adenoma/cirurgia , Colo/fisiopatologia , Colo/cirurgia , Neoplasias do Colo/cirurgia , Pólipos do Colo/cirurgia , Humanos
15.
Artigo em Inglês | MEDLINE | ID: mdl-31323378

RESUMO

BACKGROUND & AIMS: There is controversy about whether psychological factors (anxiety and depression) increase health care seeking by patients with irritable bowel syndrome (IBS). We investigated whether psychological factors increase health care seeking by patients with IBS and the effects of extragastrointestinal (extra-GI) symptoms. METHODS: We performed a population-based prospective study of health care use over a 12-year period in Sweden. From 2002 through 2006, 1244 subjects were selected randomly for an examination by a gastroenterologist and to complete questionnaires, including the Rome II modular questionnaire. Psychological factors were measured with the valid Hospital Anxiety and Depression scale and extra-GI symptoms were measured with a symptom checklist. Responses from 1159 subjects (57% female; mean age, 48.65 y) were matched with health records in 2016 (164 were classified as having IBS based on Rome II criteria). RESULTS: The overall association between depression or anxiety and health care use varied in subjects with and without IBS at baseline. The presence of extra-GI symptoms strengthened the relationship between anxiety and depression and prospective psychiatric visits for subjects with IBS and without IBS (incidence rate ratio, 1.14-1.26). Extra-GI symptoms did not alter the association of anxiety or depression with use of GI or extra-GI health care. CONCLUSIONS: In a population-based study in Sweden, we found that individuals with high baseline anxiety or depression were more likely to seek psychiatric health care, but not GI or extra-GI health care, in the presence of extra-GI symptoms at baseline. Patients with IBS might benefit from more thorough assessments that examine extra-GI and psychological symptoms, to reduce health care utilization.

18.
Arch Toxicol ; 93(8): 2211-2218, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31227841

RESUMO

New psychoactive substances, especially synthetic cannabinoids (SC), are gaining increasing relevance in postmortem forensic toxicology. Particularly, the interpretation of analytical results is challenging, as usually, no toxicokinetic (TK) data concerning distribution in organs and tissues are available. Thus, a controlled pig TK study allowing for examination of organ and tissue distribution of SC was performed. For this purpose, 12 pigs received a single pulmonary dose of 200 µg/kg body weight each of 4-ethylnaphthalene-1-yl-(1-pentylindole-3-yl)methanone (JWH-210), 2-(4-methoxyphenyl)-1-(1-pentylindole-3-yl)methanone (RCS-4), and Δ9-tetrahydrocannabinol (THC) via an ultrasonic nebulizer. Eight hours after administration, the animals were put to death by the administration of T61. Thereupon, relevant organs, important body fluids such as bile and colon content, and tissues such as muscle tissue were collected. After enzymatic hydrolysis and solid-phase extraction, analysis was performed by liquid chromatography-tandem mass spectrometry. For quantification, a standard addition method was applied. The parent compounds could be detected in every analyzed specimen with the exception of colon content. Regarding JWH-210, the kidneys and lungs are viable matrices for postmortem analysis. In terms of RCS-4, the lungs were found to be an appropriate matrix. Concerning THC, the liver, bile fluid as well as duodenum content were suitable matrices for detection. Metabolites were only detected in tissues/body fluids involved in metabolism and/or elimination. Bile fluid and duodenum content were shown, as the most appropriate specimens for quantification of metabolites.

19.
Dalton Trans ; 48(24): 8671-8677, 2019 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-31140530

RESUMO

Recently, a number of different structurally related nitrides characterized by pairs of edge-sharing Si-N tetrahedra forming [Si2N6]10- units have emerged via different synthesis methods. Concurrently, upon doping with rare earth elements (e.g. Eu2+ and Ce3+), numerous applications in the field of luminescent materials were revealed, ranging from the visible spectrum to the near IR. This compound class in turn emphasizes the extraordinary large tuning range with respect to relative composition by formal cation exchange. In this contribution, we study the dynamical stabilities of the existing Si-based nitridotetrelates and hypothetical Ge analogues promising for future synthesis efforts of luminescent materials by means of extensive phonon calculations. Further calculations of electronic and mechanical properties corroborate the fundamental suitability of the predicted compounds for the applications of potential luminescent materials with regard to band gap (Eg) and Debye temperature (ΘD). Calculated enthalpies of the reaction provide further beneficial insights for future experimental attempts. Our study hence highlights a potential range of novel stable nitridogermanates with isotypic structures and suitable electronic properties for optoelectronic applications.

20.
Front Vet Sci ; 6: 106, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31111038

RESUMO

Mast cell tumor (MCT) is the most common cutaneous neoplasm in dogs and wide surgical resection is the current first-line treatment. However, recurrence is common and often requires more specialist and expensive therapies. Tigilanol tiglate is a novel small molecule drug delivered by intratumoral injection that is currently under development to provide a new option for treating MCT. The aim of this study was to characterize a safe and effective dose of tigilanol tiglate for canine MCT and to gather preliminary data on the drug's pharmacokinetics. A multicenter, open-label, uncontrolled, non-randomized, dose de-escalation design was used. Eligibility was MCT stage I/IIa and a tumor size of 0.1-6.0 cm3. Dosing was based on tumor size (50% v/v tumor) and 3 drug concentrations (1.0, 0.5, 0.2 mg/mL) were evaluated. Twenty-seven dogs were treated in 3 dose de-escalation cohorts (10, 10, and 7 dogs, respectively). Efficacy at 21 days was defined using international accepted solid tumor response criteria (RECIST). Greatest efficacy (90% complete response) was observed at the highest drug concentration (1.0 mg/mL) and adverse events were generally low grade, mild and transient, and directly associated with the mode of action of the drug. Hematological and serum biochemistry were generally unremarkable with plasma concentration curves typical of a non-intravenous parenteral medication. Intratumoral treatment of MCT with tigilanol tiglate at a concentration of 1.0 mg/mL was highly efficacious and well-tolerated. These results support the drug's further development for the treatment of MCT and other solid tumors.

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