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1.
RSC Adv ; 14(27): 19592-19602, 2024 Jun 12.
Artículo en Inglés | MEDLINE | ID: mdl-38895529

RESUMEN

A supramolecular complex µ-meso-tetra(4-pyridyl) porphyrinate nickel(ii)tetrakis[bis(bipyridine)(chloro)ruthenium(ii)] ([NiTPyP{Ru(bipy)2Cl}4]4+) was intercalated into the interlayer space of natural smectite clay (shortened as Ba) collected in a Cameroonian deposit at Bagba hill. Physicochemical characterization of the resulting material using ultraviolet-visible spectroscopy (UV-vis), Fourier transform infrared (FTIR) spectroscopy, and X-ray diffraction (XRD) confirmed the intercalation of the porphyrin within the interlayer space of the clay. The intercalated clay was then used to form a stable thin film onto a glassy carbon electrode (GCE) by drop casting a suspension of the hybrid material. The GCE modified with the intercalated organoclay endowed the electrode with a larger electrochemically active surface area, good stability, high selectivity, and sensitivity toward dopamine (DA), acetaminophen (AC) and tryptophan (Trp). In addition, it was observed that the modified electrodes exhibited good and pH-dependent electrocatalytic properties toward these analytes. The simultaneous determination of DA, AC and Trp at [NiTPyP{Ru(bipy)2Cl}4]4+-Ba/GCE was thus possible without the interference of one analyte on the others, and the resulting calibration curve exhibits two segments for the three analytes. For DA, AC and Trp, the detection limits were found to be 0.8 µM, 0.3 µM and 0.3 µM, respectively. The [NiTPyP{Ru(bipy)2Cl}4]4+-Ba/GCE modified electrodes were successfully applied for the determination of AC in Paracetamol, a commercial product, and Trp in real pharmaceutical formulation samples.

2.
Transl Anim Sci ; 8: txad138, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38304120

RESUMEN

Twenty-six nulliparous sows were fed conventional gestation and lactation diets supplemented (N = 13) or not (N = 13) with extra daily supplements of 25-hydroxy-cholecalciferol (25-OH-D3; 4 ĸIU), ß-carotene (24 ĸIU), and copper (Cu)-proteinate (45 mg) from day 90 of gestation to 21 d of lactation (L21). In each litter, 10 piglets were divided into 5 pairs received, at 2 (L2) and 8 d (L8) of age, one of the five combinations of micronutrient sources and routes of administration (N = 260 piglets total). These neonatal treatments (N = 26 pairs or 52 piglets each) consisted of oral vitamin D3, retinol acetate and CuSO4 (T1); oral 25-OH-D3, ß-carotene, and Cu proteinate (T2); exposure to ultraviolet light (UVB), oral retinol palmitate and Cu gluconate (T3); intramuscular vitamin D3 and retinyl propionate and oral Cu acetate (T4); oral saline (CTRL). Oral or intramuscular provisions corresponded to 12 mg of Cu and 70 and 12 ĸIU of vitamins A and D, respectively. Blood samples were collected from all piglets at L2, L8, and L21 for determination of serum Cu, retinol, and 25-OH-D3. Body weight was measured at birth, L2, L8, and L21. Piglets were weaned at L21, and liver and blood samples were collected 2 d later to evaluate oxidative enzymes in blood and liver and hepatic ATP concentrations and expression of genes associated with antioxidant status. Sow treatments had marginal or no impacts on Cu, retinol, 25-OH-D3, or antioxidant status in piglet blood serum and liver. However, when supplements were given to piglets, hepatic Cu was 38% greater in for all treated piglets compared to CTRL (P < 0.01), hepatic retinol was 3 times higher in T1 than in CTRL (P < 0.01) and intermediate for other treatments whereas serum 25-OH-D3 was markedly increased with T2 and T3 at L8 and L21, respectively, compared to CTRL (Piglet treatment × Age interaction, P < 0.01). Concerning antioxidant activities, glutathione peroxidase, and superoxide dismutase were increased (P < 0.03) in plasma of T2 piglets whereas the highest values (P < 0.03) for indicators of oxidative damage to proteins were observed in T4 piglets. The study revealed that oral Cu proteinate from T2, oral retinol acetate from T1, oral 25-hydroxy-cholecalciferol from T2, and UVB light exposure from T3 were the most efficient ways of increasing the postnatal status of these micronutrients in suckling piglets and this may have some impacts on their peri-weaning antioxidant status.

3.
J Water Health ; 21(10): 1460-1469, 2023 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-37902202

RESUMEN

The specific contributions of the different bacterial flora during the biological treatment of slaughterhouse effluents remain unclear. The objective of this study is to identify the different microbial flora which mainly contribute to the efficiency of the biodegradation of the organic, nitrogenous and phosphate loads contained in the slaughterhouse effluent during its biological treatment. To achieve this, the effluent to be treated was sampled from three slaughterhouses in the city of Ngaoundéré (Cameroon). The various effluents underwent a physicochemical and microbiological characterization. The effluent was subjected to biological treatment. The biodegradation process (biological treatment) took place in two reactors, each operating in batch. One of the two reactors was supplied with oxygen (aeration). The effluent being treated underwent a physicochemical and microbiological characterization for 30 days. The results obtained show organic matter and ammonium contents >1,000 mgO2/L in each of the three effluents. Bacillus cereus (69 × 108 CFU/mL), Pseudomonas aeruginosa (201 × 107 colony forming unit (CFU)/mL) and Yeasts (101 × 106 CFU/mL) globally constitute the majority of microbial groups among the seven microorganisms identified in the effluents of the three slaughterhouses. There is no real oxygenation effect of the medium on the growth of the three microbial flora during the treatment.


Asunto(s)
Mataderos , Fenómenos Biológicos , Pseudomonas aeruginosa , Camerún
4.
J Water Health ; 21(8): 1017-1031, 2023 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-37632378

RESUMEN

Orange peel powder was activated using different methods and was used to remove tartrazine (E102) from an aqueous solution. The following three adsorbents were synthethized: orange peel powder activated thermally (POAT), orange peel powder activated with sulfuric acid (POAA), orange peel powder activated with soda (POAS). These adsorbents were then characterized by Fourier Transform Infra-Red Spectrometry (FTIR), Raman spectroscopy, powder X-Ray Diffraction (XRD), and point-of-zero charge. The experimental parameters such as contact time, dose of adsorbent, initial concentration of tartrazine, pH, and temperature were studied. The adsorption capacities of tartrazine for the optimal POAT, POAA, and POAS were found to be 121.74, 122.25, and 116.35 mg/g, respectively. The experimental data were analyzed by Freundlich and Temkin isotherm models, as well as the pseudo-second-order kinetic model.


Asunto(s)
Citrus sinensis , Tartrazina , Adsorción , Polvos , Cinética
5.
Foods ; 12(8)2023 Apr 20.
Artículo en Inglés | MEDLINE | ID: mdl-37107508

RESUMEN

Mycotoxins are naturally occurring toxins that contaminate different crops and foodstuffs under certain circumstances during harvesting, handling, storage, and processing. Neither the dietary intake of mycotoxins in Cameroon is well characterized, nor its health effects on the consumers. This review is intended to be the first milestone towards national risk management of mycotoxins. It is noteworthy that mycotoxins contaminate the main staple foods of Cameroonian communities, which are also often used as complementary foods for infants, young children, and people with compromised immune systems (e.g., HIV/AIDS), thus calling for urgent intervention in primary and secondary prevention. Very few data exist on mycotoxin contamination in Cameroonian agricultural commodities and food items. Only 25 studies from 14 different authors have been published in the last decade. On the basis of available data in Cameroon, the Estimated Daily Intake (EDI) of major mycotoxins in foods for Aflatoxins was 0.0018-14.2 µg/kgbw/day in maize, 0.027-2.36 µg/kgbw/day in cassava, and 0.023-0.1 µg/kgbw/day in groundnuts. The estimated daily intake of fumonisins was 0.12-60.6 µg/kgbw/day in maize and 0.056-0.82 µg/kgbw/day in beans. Based on the estimated distribution of human exposure levels by food, maize and cassava are the major sources of exposure and should be prioritized, followed by beans and spices. This estimate will be updated along with improvements on the national database on mycotoxin contamination of Cameroonian foods.

6.
J Nutr ; 153(1): 96-105, 2023 01.
Artículo en Inglés | MEDLINE | ID: mdl-36913483

RESUMEN

BACKGROUND: Natural products rich in polyphenols have been shown to lower plasma trimethylamine-n-oxide (TMAO) known for its proatherogenic effects by modulating the intestinal microbiota. OBJECTIVES: We aimed to determine the impact of Fruitflow, a water-soluble tomato extract, on TMAO, fecal microbiota, and plasma and fecal metabolites. METHODS: Overweight and obese adults (n = 22, BMI 28-35 kg/m2) were included in a double-blind, placebo-controlled, cross-over study receiving 2×150 mg Fruitflow per day or placebo (maltodextrin) for 4 wk with a 6-week wash-out between interventions. Stool, blood, and urine samples were collected to assess changes in plasma TMAO (primary outcome) as well as fecal microbiota, fecal and plasma metabolites, and urine TMAO (secondary outcomes). In a subgroup (n = 9), postprandial TMAO was evaluated following a choline-rich breakfast (∼450 mg). Statistical methods included paired t-tests or Wilcoxon signed rank tests and permutational multivariate analysis of variance. RESULTS: Fruitflow, but not placebo, reduced fasting levels of plasma (-1.5 µM, P ≤ 0.05) and urine (-19.1 µM, P ≤ 0.01) TMAO as well as plasma lipopolysaccharides (-5.3 ng/mL, P ≤ 0.05) from baseline to the end of intervention. However, these changes were significant only for urine TMAO levels when comparing between the groups (P ≤ 0.05). Changes in microbial beta, but not alpha, diversity paralleled this with a significant difference in Jaccard distance-based Principal Component (P ≤ 0.05) as well as decreases in Bacteroides, Ruminococccus, and Hungatella and increases in Alistipes when comparing between and within groups (P ≤ 0.05, respectively). There were no between-group differences in SCFAs and bile acids (BAs) in both faces and plasma but several changes within groups such as an increase in fecal cholic acid or plasma pyruvate with Fruitflow (P ≤ 0.05, respectively). An untargeted metabolomic analysis revealed TMAO as the most discriminant plasma metabolite between groups (P ≤ 0.05). CONCLUSIONS: Our results support earlier findings that polyphenol-rich extracts can lower plasma TMAO in overweight and obese adults related to gut microbiota modulation. This trial was registered at clinicaltrials.gov as NCT04160481 (https://clinicaltrials.gov/ct2/show/NCT04160481?term= Fruitflow&draw= 2&rank= 2).


Asunto(s)
Microbioma Gastrointestinal , Solanum lycopersicum , Adulto , Humanos , Sobrepeso , Estudios Cruzados , Obesidad , Metilaminas/metabolismo , Óxidos
7.
Chemosphere ; 217: 833-842, 2019 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-30453277

RESUMEN

The photocatalytic degradation of atrazine by activated carbon/graphitic carbon nitride composites with peroxymonosulfate (PMS) was investigated under visible light irradiation. The photocatalysts were prepared at different activated carbon (AC) loaded percentages and characterized by XRD, FT-IR, BET surface area, SEM, UV-Vis absorbance, photocurrent response and EIS. Several parameters which might influence the degradation efficiency were studied including PMS concentration, solution pH, catalyst dosage, initial atrazine concentration as well as water matrix effect. The results indicated that incorporation of AC contributes effectively in suppressing the recombination of electron-holes pairs and enhancing the photocatalytic performance of graphitic carbon nitride. More significantly, the degradation efficiency of atrazine showed remarkable improvement with PMS addition under visible light irradiation. The reaction rate constant of the 10% AC/g-C3N4/Vis/PMS system (0.0376 min-1) was approximately 2.9 times higher than that of g-C3N4/Vis/PMS system (0.0128 min-1). Results from quenching tests revealed that both sulfate and hydroxyl radicals were involved in the degradation of atrazine, while the latter is the main contributor. This paper constitutes an insight for the metal-free catalyst activation of PMS by photocatalysis for environmental remediation.


Asunto(s)
Atrazina/química , Luz , Nitrilos/química , Peróxidos/química , Fotólisis , Atrazina/efectos de la radiación , Catálisis , Carbón Orgánico , Restauración y Remediación Ambiental , Grafito/química , Análisis Espectral
8.
Toxics ; 5(4)2017 Nov 01.
Artículo en Inglés | MEDLINE | ID: mdl-29104250

RESUMEN

Chemical pesticides are widely used in Cameroon for agricultural production. In 2015, more than 600 pesticide products were approved for use in various foodstuffs. Much misuse of these chemicals by farmers has been documented in rural and urban settings. This pilot study aims to contribute to the improvement of the health of the population and the environmental preservation by identifying pesticide-poisoning cases, the most incriminated products and critical risk factors of exposure. Questionnaires were administered to pesticide vendors, farmers and health personnel, and observations made on farmers' practices at their work places. From July to September 2016, 24 villages from five sites, representing the most important agricultural production areas of the five agro-ecological zones of Cameroon, were visited. In total, 519 people were interviewed: 412 farmers, 69 pesticide vendors and 38 health personnel. A total of 180 pesticide formulations out of 610 registered in 2015 were said to be used by farmers. In the 38 health centers visited, 56 cases of pesticide poisonings and intoxications were reported between 2011 and 2016. Paraquat-, glyphosate-, cypermethrin- and metalaxyl-formulated pesticides were the most incriminated. In total, 78% of poisoning cases were accidental, 12% suicide attempts, 4% criminal. Entry of pesticide products from neighboring countries needs to be better regulated, and the quality of pesticides sold on the market should be monitored periodically. Empty pesticide containers should be recuperated from smallholder farmers. Authorities should set up a harmonized pesticide-poisoning management procedure, and create a toxico-vigilance system for surveillance cases and preventive actions.

9.
Toxicol Rep ; 4: 474-483, 2017.
Artículo en Inglés | MEDLINE | ID: mdl-28959677

RESUMEN

The Egusi Okra soup is a traditional African meal that is considered of high nutritional value and protective against weight loss. We introduce the concept of "kitchen toxicology" to analyse the recipe of the Egusi Okra soup and highlight possible mitigation measures for toxic and/or antinutritional effects in the wide spectrum of health and nutritional needs of HIV+/AIDS subjects. In particular, we focus on toxicants (environmental contaminants, process contaminants, substances leaching from food contact materials) dysregulating the immune status, as well as on interactions between nutrients, contaminants, and/or antinutrients which may lead to secondary/conditioned nutritional deficiencies or imbalances; in their turn, these can modulate the ability to cope with toxicants, and increase nutritional requirements. Recommendations are given for practices preserving the Egusi Okra soup from such risk factors, identifying points of particular attention during meal preparation, from purchase of raw ingredients through to food handling, cooking, storage, and consumption. The Egusi Okra soup is discussed in the context of a diet that is asked to mitigate complications (weight loss, opportunistic infections) and support antiretroviral therapy in African countries with high HIV/AIDS prevalence. The paper discusses how nutritional interventions benefit of the integration of kitchen toxicology practices in everyday life. Toxicological risk assessment is crucial to understand the history and status of the person exposed to or affected by infectious diseases.

10.
Sci Total Environ ; 566-567: 1465-1471, 2016 Oct 01.
Artículo en Inglés | MEDLINE | ID: mdl-27342642

RESUMEN

The term geophagy is applied to the recurrent intentional eating of soil with multifactorial motivation. Geophagists are generally defined by gender (women), age (children), physical status (e.g. pregnancy, lactation, postpartum), social status (people exposed to significant nutritional deficiencies), and culture, but lost awareness of traditional medical meaning of this practice is changing these consumption patterns and increasing health risks. Moreover, although the holistic anthropological perspective recognizes soil consumption as mineral supplementation under certain circumstances, we should consider how the living environment has changed and is changing, along with diet, nutrition requirements, and habits. Therefore, benefits-to-risks ratio of cultural behaviours initiated centuries ago based on traditional medical practices requires deep revision and assessment. Knowledge on minerals metabolism, bioavailability and interactions is required to properly assess the role of geophagy in a balanced and safe intake of micronutrients. Most important, the risk of unbalanced intake of minerals may be serious since the mineralogy and chemistry of geophagic clays are uncontrolled, variable, and difficult to standardize. In addition, other factors (radioactive materials, organic chemicals and soil pathogens) complicate the risk assessment for population groups consuming soil. Since the geophagic practice is expected to persist despite economic development, the paper discusses the multifaceted spectrum of geophagy to highlight critical aspects for risk management.


Asunto(s)
Ingestión de Alimentos , Medicina Tradicional , Estado Nutricional , Suelo , Dieta , Humanos , Minerales/análisis , Medición de Riesgo , Suelo/química , Contaminantes del Suelo/efectos adversos
11.
Bioorg Med Chem ; 23(17): 5433-51, 2015 Sep 01.
Artículo en Inglés | MEDLINE | ID: mdl-26277760

RESUMEN

17ß-Hydroxysteroid dehydrogenase type 3 (17ß-HSD3) is a key enzyme involved in the biosynthesis of testosterone and dihydrotestosterone. These hormones are known to stimulate androgen-dependent prostate cancer. In order to generate effective inhibitors of androgen biosynthesis without androgenic effect, we synthesized a new family of 3-spiromorpholinone and 3-spirocarbamate androsterone derivatives bearing diversified hydrophobic groups. We also tested their inhibitory activity in a microsomal fraction of 17ß-HSD3-containing rat testes, and their androgenic effect on androgen-sensitive LAPC-4 cells. From our first structure-activity relationship (SAR) study, we noted that compound 7e inhibited 17ß-HSD3 (77% at 0.1 µM) compared to our reference compound RM-532-105 (76% at 0.1 µM), but exhibited a residual androgenic effect. A library of 7e analogue compounds was next synthesized in order to generate compounds with reduced androgenic activity. In this new SAR study, the sulfonamide compound 7e21 and the carboxamide compound 7e22 inhibited 17ß-HSD3 (IC50 = 28 and 88 nM, respectively). These two compounds were not androgenic and not cytotoxic even at the highest concentration tested, but their inhibitory activity decreased in intact LNCaP cells overexpressing 17ß-HSD3 (LNCaP[17ß-HSD3]). Structural modifications of these two lead compounds could however be tested to produce a second generation of 17ß-HSD3 inhibitors.


Asunto(s)
17-Hidroxiesteroide Deshidrogenasas/antagonistas & inhibidores , Carbamatos/química , Carbamatos/farmacología , Morfolinas/química , Morfolinas/farmacología , Compuestos de Espiro/química , Compuestos de Espiro/farmacología , 17-Hidroxiesteroide Deshidrogenasas/metabolismo , Andrógenos/química , Andrógenos/farmacología , Animales , Línea Celular Tumoral , Diseño de Fármacos , Inhibidores Enzimáticos/química , Inhibidores Enzimáticos/farmacología , Humanos , Masculino , Próstata/efectos de los fármacos , Próstata/enzimología , Neoplasias de la Próstata/tratamiento farmacológico , Neoplasias de la Próstata/enzimología , Ratas
12.
Environ Technol ; 35(13-16): 1831-9, 2014 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-24956776

RESUMEN

In this study, spatial and seasonal variations of phosphorus fractions in Lake Bini sediments were evaluated using a sequential extraction method. The sampling of water and sediments (surface and coring) was carried out at seven sites around the lake during the dry season and the rainy season. The results showed that phosphorus is mainly in the inorganic form (L-P+Ca-P+Fe-P) in the sediments whatever the season may be. The rank order of phosphorus extracts obtained was Fe-P>Ca-P>OM-P>L-P>Res-P. The maximum values of phosphorus (sum of each fraction) were obtained in the rainy season at the sites D6 (298.12 +/- 12.37 microg P/g) and D4 (244.93 +/- 11.06 microg P/g) located beside water source 2 and farmland 2, respectively. The average values of the phosphorus content vary from 05.29 +/- 1.05 microg P/g to 102.58 +/- 4.62 microg P/g for the upper layer (0-5 cm depth); 04.67 +/- 0.66 microg P/g to 70.06 +/- 2.82 microg P/g for the medium layer (5-10 cm depth) and finally 04.63 +/- 0.98 microg P/g to 55.24 +/- 5.17 microg P/g for the deep layer (10-15 cm depth). The results of principal component analysis showed that processes which enhance Ca-P and Fe-P accumulation are probably related to the same factor and the origin of P depends on the source of pollution. The nature of the season plays a significant role in the geochemical composition of the sediments in phosphorus and on the eutrophication level of Lake Bini.


Asunto(s)
Sedimentos Geológicos/química , Fósforo/química , Camerún , Carbonatos/química , Hierro/química , Lagos/química , Análisis de Componente Principal , Estaciones del Año
13.
Sci Total Environ ; 481: 296-302, 2014 May 15.
Artículo en Inglés | MEDLINE | ID: mdl-24602914

RESUMEN

The plasticizer Bisphenol A (BPA) is banned in baby bottles in many industrialized countries due to safety concerns. We provide a pilot view on the potential BPA exposure of bottle-fed children in sub-Saharan Africa through an enquiry on availability, accessibility and affordability of plastic baby bottles, usage pattern, and risk perception. An observational survey was conducted in a randomized group of vending sites (34 pharmacies; 87 shops and markets), in three cities (Yaoundé, Foumbot, Bafoussam) in Cameroon (two regions), and in two cities (Lagos, Port Harcourt) in Nigeria (two states). Interviews in vending sites and group discussions were conducted with 248 mothers. Cameroon and Nigeria showed a largely comparable situation. Plastic baby bottles are largely imported from industrialized countries, where a label indicates the presence/absence of BPA. In pharmacies most plastic baby bottles are labeled as BPA-free, whereas most bottles sold in shops are not BPA-free. BPA-containing bottles are more accessible and affordable, due to sale in common shops and lower costs. The meaning of the label BPA-free is unknown to both vendors and customers: the BPA issue is also largely unknown to policy makers and media and no regulation exists on food contact materials. The wide availability of BPA-containing baby bottles, lack of information and usage patterns (e.g. temperature and duration of heating) suggest a likely widespread exposure of African infants. Possible usage recommendations to mitigate exposure are indicated. Risk communication to policy makers, sellers and citizens is paramount to raise awareness and to oppose possible dumping from countries where BPA-containing materials are banned. Our pilot study points out relevant global health issues such as the capacity building of African communities on informed choices and usage of baby products, and the exploitation of international knowledge by African scientists and risk managers.


Asunto(s)
Compuestos de Bencidrilo/análisis , Alimentación con Biberón/estadística & datos numéricos , Exposición a Riesgos Ambientales/estadística & datos numéricos , Contaminación de Alimentos/estadística & datos numéricos , Sustancias Peligrosas/análisis , Fenoles/análisis , Camerún , Exposición a Riesgos Ambientales/prevención & control , Contaminación de Alimentos/prevención & control , Humanos , Lactante , Medición de Riesgo , Gestión de Riesgos
14.
Bioorg Med Chem Lett ; 23(23): 6360-2, 2013 Dec 01.
Artículo en Inglés | MEDLINE | ID: mdl-24144853

RESUMEN

Spiromorpholinone derivatives were synthesized from androsterone or cyclohexanone in 6 or 3 steps, respectively, and these scaffolds were used for the introduction of a hydrophobic group via a nucleophilic substitution. Non-steroidal spiromorpholinones are not active as inhibitors of 17ß-hydroxysteroid dehydrogenase type 3 (17ß-HSD3), but steroidal morpholinones are very potent inhibitors. In fact, those with (S) stereochemistry are more active than their (R) homologues, whereas N-benzylated compounds are more active than their non substituted precursors. The target compounds exhibited strong inhibition of 17ß-HSD3 in rat testis homogenate (87-92% inhibition at 1 µM).


Asunto(s)
17-Hidroxiesteroide Deshidrogenasas/antagonistas & inhibidores , Androsterona/análogos & derivados , Inhibidores Enzimáticos/síntesis química , Inhibidores Enzimáticos/farmacología , 17-Hidroxiesteroide Deshidrogenasas/metabolismo , Androsterona/síntesis química , Animales , Masculino , Ratas , Relación Estructura-Actividad , Testículo/enzimología
15.
Molecules ; 18(1): 914-33, 2013 Jan 11.
Artículo en Inglés | MEDLINE | ID: mdl-23344201

RESUMEN

We synthesized two series of androstane derivatives as inhibitors of type 3 and type 5 17ß-hydroxysteroid dehydrogenases (17ß-HSDs). In the first series, four monospiro derivatives at position C17 were prepared from androsterone (ADT) or epi-ADT. After the protection of the alcohol at C3, the C17-ketone was alkylated with the lithium acetylide of tetrahydro-2-(but-3-ynyl)-2-H-pyran, the triple bond was hydrogenated, the protecting groups hydrolysed and the alcohols oxidized to give the corresponding 3-keto-17-spiro-lactone derivative. The other three compounds were generated from this keto-lactone by reducing the ketone at C3, or by introducing one or two methyl groups. In the second series, two dispiro derivatives at C3 and C17 were prepared from epi-ADT. After introducing a spiro-δ-lactone at C17 and an oxirane at C3, an aminolysis of the oxirane with L-isoleucine methyl ester provided an amino alcohol, which was treated with triphosgene or sodium methylate to afford a carbamate- or a morpholinone-androstane derivative, respectively. These steroid derivatives inhibited 17ß-HSD3 (14-88% at 1 µM; 46-94% at 10 µM) and 17ß-HSD5 (54-73% at 0.3 µM; 91-92% at 3 µM). They did not produce any androgenic activity and did not bind steroid (androgen, estrogen, glucocorticoid and progestin) receptors, suggesting a good profile for prostate cancer therapy.


Asunto(s)
17-Hidroxiesteroide Deshidrogenasas/antagonistas & inhibidores , Androstanos/síntesis química , Antineoplásicos Hormonales/síntesis química , 17-Hidroxiesteroide Deshidrogenasas/biosíntesis , Androstanos/farmacología , Antineoplásicos Hormonales/farmacología , Carbamatos/síntesis química , Carbamatos/farmacología , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Células HEK293 , Humanos , Lactonas/síntesis química , Lactonas/farmacología , Morfolinas/síntesis química , Morfolinas/farmacología , Relación Estructura-Actividad
17.
Acta Crystallogr C ; 68(Pt 6): o231-4, 2012 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-22669194

RESUMEN

The title compounds, (3R,5S,5'R,8R,9S,10S,13S,14S)-10,13-dimethyl-5'-(2-methylpropyl)tetradecahydro-6'H-spiro[cyclopenta[a]phenanthrene-3,2'-[1,4]oxazinane]-6',17(2H)-dione, C(26)H(41)NO(3), (I), and methyl (2R)-2-[(3R,5S,8R,9S,10S,13S,14S)-10,13-dimethyl-2',17-dioxohexadecahydro-3'H-spiro[cyclopenta[a]phenanthrene-3,5'-[1,3]oxazolidin-3'-yl]]-4-methylpentanoate, C(28)H(43)NO(5), (II), possess the typical steroid shape (A-D rings), but they differ in their extra E ring. The azalactone E ring in (I) shows a half-chair conformation, while the carbamate E ring of (II) is planar. The orientation of the E-ring substituent is clearly established and allows a rationalization of the biological results obtained with such androsterone derivatives.


Asunto(s)
Antagonistas de Andrógenos/química , Antagonistas de Andrógenos/farmacología , Andrógenos/biosíntesis , Andrógenos/química , Androsterona/química , Androsterona/farmacología , Androsterona/análogos & derivados , Cristalografía por Rayos X , Modelos Moleculares
18.
Artículo en Inglés | MEDLINE | ID: mdl-22541169

RESUMEN

A liquid chromatography/tandem mass spectrometry (HPLC-MS/MS) method was validated for the quantification of Sotrastaurin (AEB071) and N-desmethyl-sotrastaurin in human blood. The validation of the analytical procedure was performed according to the latest Food and Drug Administration (FDA) "Guidance for Industry, Bioanalytical Method Validation". Chromatographic separation was performed using an RP C18 (50 mm × 4.6 mm, 5 µm) column at 40±3.0 °C with a mobile phase consisted of 2 mM ammonium acetate in water (pH 4.5):methanol:acetonitrile (25:15:60, v/v) of a flow rate of 1 mL/min followed by quantification with tandem mass spectrometer, operated in electrospray ionization (ESI) positive ion mode and applying multiple reaction monitoring (MRM). The validated method described in this paper presents high absolute recovery, with a sensitivity of 3.00 ng/mL as lower limit of quantitation using a sample volume of 300 µL, low inter-run bias and variability (for Sotrastaurin, -4.4 to 0.4% and 1.8 to 2.5% and for N-desmethyl-sotrastaurin, ranged from 1.6 to 2.3% and 2.7 to 3.9%, respectively) with a short runtime of 3.5 min. The method was validated using K3EDTA as specific anticoagulant and cross-validated using Li-Heparin and Na-Heparin. The method was specific for Sotrastaurin and N-desmethyl-sotrastaurin within the given criteria of acceptance (apparent peak area for Sotrastaurin and N-desmethyl-sotrastaurin in zero samples ≤ 20% of mean peak area at LLOQ) in human blood. The method was fully validated for the quantitative determination of Sotrastaurin and its metabolite N-desmethyl-sotrastaurin in human blood between the range of 3.00 ng/mL and 1200 ng/mL.


Asunto(s)
Cromatografía Líquida de Alta Presión/métodos , Pirroles/sangre , Quinazolinas/sangre , Cromatografía Líquida de Alta Presión/normas , Estabilidad de Medicamentos , Humanos , Análisis de los Mínimos Cuadrados , Pirroles/química , Pirroles/metabolismo , Quinazolinas/química , Quinazolinas/metabolismo , Reproducibilidad de los Resultados , Sensibilidad y Especificidad , Espectrometría de Masas en Tándem/métodos
19.
Indian J Pharmacol ; 40(6): 266-70, 2008 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-21279183

RESUMEN

AIM: The antioxidant effect of the methanol-methylene chloride extract of Terminalia glaucescens (Combretaceae) leaves was investigated in streptozotocin (STZ)-induced oxidative stress. METHODS: Oxidative stress was induced in mice by a daily dose of STZ (45 mg/kg body weight i.p.) for five days. From day one, before STZ injection, normal and diabetic-test mice received an oral dose of the extract (100 or 300 mg/kg b.w.) daily. Plasma metabolites, lipid peroxidation, and antioxidant enzymes in the liver were assessed and gain in body weight recorded. RESULTS: In normal mice the plant extract reduced food and water intake, blood glucose and LDL-C level and body weight gain, did not affect the lipid peroxidation in the liver, while the antioxidant enzyme activities seemed increased. Blood glucose was decreased (P < 0.05) in normal mice treated with 300 mg/kg extract. Diabetic mice pretreated with 100 mg/kg extract as diabetic control mice (DC) showed significant (P < 0.001) body weight loss, polyphagia and polydipsia, high plasma glucose level, decrease in the liver catalase, peroxidase, and superoxide dismutase activities, and increase in lipid peroxidation. The HDL-C level was lowered (P < 0.05) whereas LDL-C increased. In 300 mg/kg extract-pretreated diabetic mice the extract prevented body weight loss, increase of blood glucose level, lipid peroxidation in liver, food and water intake, and lowering of plasma HDL-C level and liver antioxidants; this extract prevented LDL-C level increase. CONCLUSION: These results indicate that T. glaucescens protects against STZ-induced oxidative stress and could thus explain its traditional use for diabetes and obesity treatment or management.

20.
Surg Technol Int ; 10: 109-14, 2002 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-12384872

RESUMEN

The laparoscopic application of an adjustable silicone gastric band (Lap-Band System, Bioenterics, Carpinteria, CA) (Fig. 1), based on a similar device introduced by Kuzmak in 1986, is gaining widespread acceptance as a gastric restrictive procedure in treatment of morbid obesity. The advantage of an operation that does not open the gastrointestinal tract and can be performed laparoscopically is obvious. This procedure, using the laparoscopic approach , has been performed in our institutions since 1992. The goals of this article are to describe both our standardized surgical technique that minimized the morbidity rate and its results.


Asunto(s)
Gastroplastia/métodos , Laparoscopía , Obesidad Mórbida/cirugía , Adolescente , Adulto , Anciano , Femenino , Gastroplastia/instrumentación , Humanos , Masculino , Persona de Mediana Edad , Siliconas
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