Browsing by Autor "Silvia Zambrana"

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Amaranthus caudatus extract inhibits the invasion of E. coli into uroepithelial cells
(Elsevier BV, 2018) Soumitra Mohanty; Silvia Zambrana; Soizic Dieulouard; Witchuda Kamolvit; Vera Nilsén; Eduardo Gonzáles; Claes‐Göran Östenson; Annelie Brauner
Amaranthus caudatus Stimulates Insulin Secretion in Goto-Kakizaki Rats, a Model of Diabetes Mellitus Type 2
(Multidisciplinary Digital Publishing Institute, 2018) Silvia Zambrana; Lena Lundqvist; Virginia Veliz; Sergiu‐Bogdan Catrina; Eduardo Gonzáles; Claes‐Göran Östenson
Diabetes Mellitus Type 2 prevalence is increasing worldwide; thus efforts to develop novel therapeutic strategies are required. Amaranthus caudatus (AC) is a pseudo-cereal with reported anti-diabetic effects that is usually consumed in food preparations in Bolivia. This study evaluated the anti-diabetic nutraceutical property of an AC hydroethanolic extract that contains mainly sugars and traces of polyphenols and amino acids (as shown by nalysis with liquid chromatography-mass spectrometry (LC-MS) and nuclear magnetic resonance (NMR)), in type 2 diabetic Goto-Kakizaki (GK) rats and healthy Wistar (W) rats. A single oral administration of AC extract (2000 mg/kg body weight) improved glucose tolerance during Oral Glucose Tolerance Tests (OGTT) in both GK rats and in W rats. Long-term treatment (21 days) with AC (1000 mg/kg b.w.) improved the glucose tolerance evaluated by the area under the curve (AUC) of glucose levels during the OGTT, in both GK and W rats. The HbA1c levels were reduced in both GK (19.83%) and W rats (10.7%). This effect was secondary to an increase in serum insulin levels in both GK and W rats and confirmed in pancreatic islets, isolated from treated animals, where the chronic AC exposure increased the insulin production 4.1-fold in GK and 3.7-fold in W rat islets. Furthermore, the effect of AC on in vitro glucose-dependent insulin secretion (16.7 mM glucose) was concentration-dependent up to 50 mg/mL, with 8.5-fold increase in GK and 5.7-fold in W rat islets, and the insulin secretion in perifused GK and W rat islets increased 31 and nine times, respectively. The mechanism of action of AC on insulin secretion was shown to involve calcium, PKA and PKC activation, and G-protein coupled-exocytosis since the AC effect was reduced 38% by nifedipine (L-type channel inhibitor), 77% by H89 (PKA inhibitor), 79% by Calphostine-C (PKC inhibitor) and 20% by pertussis toxin (G-protein suppressor).
Estudio preliminar del control bacteriológico en cosméticos de preparación artesanal comercializados en la ciudad de La Paz
(2025) Yesenia Maria Angola Silvera; J.A. Sánchez Pérez; Ana Mendoza; Eduardo Gonzáles; Silvia Zambrana
El control de calidad de los cosméticos artesanales es fundamental debido a que no están sujetos a regulaciones sanitarias, lo que puede representar un riesgo para la salud de los consumidores. Los cosméticos, por su contenido de humedad y nutrientes, son propensos a transportar microorganismos patógenos, considerando que se aplican principalmente sobre la piel. Objetivo: Determinar la presencia o ausencia de microorganismos patógenos en cosméticos artesanales y controlados, en base a las normativas de calidad microbiológica. Metodología: Se analizaron 10 cosméticos artesanales y 4 controlados con registro sanitario en AGEMED. Bajo condiciones estériles, se sembraron las muestras en caldos y luego en agar nutritivo mediante el método de placa para observar el crecimiento de colonias y realizar un recuento de UFC. Posteriormente, se usaron agar sangre, medios selectivos y pruebas bioquímicas para describir e identificar los microorganismos patógenos. Resultados: Tres cosméticos artesanales mostraron contaminación microbiana: Agua micelar: 15x10⁶ UFC/mL con Enterococcus spp; Crema de naranja: 1x10⁴ UFC/mL con Enterococcus spp; Crema de rosas: 4x10⁶ UFC/mL con Escherichia coli. Los cosméticos controlados no presentaron contaminación. Conclusiones: Se identificaron microorganismos bacterianos patógenos en los cosméticos artesanales analizados, lo que incumple las normativas microbiológicas y pone en evidencia riesgos significativos para el consumidor. Esto resalta la importancia de controles rigurosos en productos cosméticos, especialmente en los de fabricación artesanal.
Extract of Clinopodium bolivianum protects against E. coli invasion of uroepithelial cells
(Elsevier BV, 2017) Soumitra Mohanty; Witchuda Kamolvit; Silvia Zambrana; Corine Sandström; Eduardo Gonzáles; Claes‐Göran Östenson; Annelie Brauner
Glycemia-reducing effects of Bolivian nutraceutical plants
(Universidad de Granada, 2021) Silvia Zambrana; Orlando Mamani Rodríguez; Mabel Canaviri; María del Pilar Gutiérrez; Sergiu‐Bogdan Catrina; Claes‐Göran Östenson; Eduardo Gonzáles
Introduction: The prevalence of diabetes type 2 is increasing worldwide, thus the search of novel alternative therapies is needed. According to their traditional use, we selected five Bolivian plants Chenopodium quinoa (CQ) Amaranthus caudatus (AC), Chenopodium pallidicaule (CP), Lupinus mutabilis (LM) and Smallanthus sonchifolius (SS) that\nare traditionally used to control glycemia.\nMethods: The effect of a single oral administration of Ethanolic (EtOH), hydro-ethanolic (EtOH70) and aqueous (Aq)\nextracts from all plant species were tested for their effect on blood glucose in non-fasted mice and during the oral\nglucose tolerance test (OGTT). The effect on insulin secretion was evaluated in mice pancreatic islets.\nResults: EtOH70 extracts of all the plants showed glucose-reducing effect at the highest dose evaluated (2000 mg/\nkg b.w.). EtOH70 extracts improved the glucose tolerance evaluated by the OGTT in mice fasted for 12 hours. The\nextracts have different effects on glucose homeostasis since just extracts of AC, LM and CQ but not CP and SS increased insulin secretion as shown on mice pancreatic islets. The phytochemical qualitative characterization of\nEtOH70 extracts detected phenolic acids and flavonoids in AC, CP and CQ; alkaloids in LM and anthocyanidins in SS.\nNone of EtOH70 extracts tested showed in vitro or in vivo acute toxicity at concentrations where they exhibit glucose\nlowering effects.\nConclusions: We report here that extracts from AC, CQ, CP, LM and SS exhibit glucose lowering effect while just AC,\nCQ and LM stimulate directly the insulin secretion.
HIF-1 mediated activation of antimicrobial peptide LL-37 in type 2 diabetic patients
(Springer Science+Business Media, 2021) Soumitra Mohanty; Witchuda Kamolvit; Silvia Zambrana; Eduardo Gonzáles; Jonas Tovi; Kerstin Brismar; Claes‐Göran Östenson; Annelie Brauner
Infections are common in patients with diabetes, but increasing antibiotic resistance hampers successful bacterial clearance and calls for alternative treatment strategies. Hypoxia-inducible factor 1 (HIF-1) is known to influence the innate immune defense and could therefore serve as a possible target. However, the impact of high glucose on HIF-1 has received little attention and merits closer investigation. Here, we show that higher levels of proinflammatory cytokines and CAMP, encoding for the antimicrobial peptide cathelicidin, LL-37, correlate with HIF-1 in type 2 diabetic patients. Chemical activation of HIF-1 further enhanced LL-37, IL-1β, and IL-8 in human uroepithelial cells exposed to high glucose. Moreover, HIF-1 activation of transurethrally infected diabetic mice resulted in lower bacterial load. Drugs activating HIF-1 could therefore in the future potentially have a therapeutic role in clearing bacteria in diabetic patients with infections where antibiotic treatment failed. KEY MESSAGES: • Mohanty et al. "HIF-1 mediated activation of antimicrobial peptide LL-37 in type 2 diabetic patients." • Our study highlights induction of the antimicrobial peptide, LL-37, and strengthening of the innate immunity through hypoxia-inducible factor 1 (HIF-1) in diabetes. • Our key observations are: 1. HIF-1 activation increased LL-37 expression in human urothelial cells treated with high glucose. In line with that, we demonstrated that patients with type 2 diabetes living at high altitude had increased levels of the LL-37. 2. HIF-1 activation increased IL-1β and IL-8 in human uroepithelial cells treated with high glucose concentration. 3. Pharmacological activation of HIF-1 decreased bacterial load in the urinary bladder of mice with hereditary diabetes. • We conclude that enhancing HIF-1 may along with antibiotics in the future contribute to the treatment in selected patient groups where traditional therapy is not possible.
Lupinus mutabilis Edible Beans Protect against Bacterial Infection in Uroepithelial Cells
(Hindawi Publishing Corporation, 2018) Witchuda Kamolvit; Vera Nilsén; Silvia Zambrana; Soumitra Mohanty; Eduardo Gonzáles; Claes‐Göran Östenson; Annelie Brauner
Lupinus mutabilis is a South American herb with edible beans, known to reduce serum glucose levels in diabetic patients. Furthermore, L. mutabilis contains phytochemicals known to decrease bacterial load. Based on the increased urinary tract infections experienced among patients with diabetes, we investigated the effect of L. mutabilis on bladder epithelial cells in the protection of E. coli infection during normal and high glucose concentrations. We did not observe any direct antibacterial effect by L. mutabilis extract. Instead we observed an influence on the host cells, with indirect impact on bacteria and their possibility of causing infection. L. mutabilis extract decreased adhesion to bladder epithelial cells of uropathogenic bacteria, including drug-resistant strains. Moreover, uroplakin1a, involved in adhesion, was downregulated while the antimicrobial peptide RNase 7 was upregulated in L. mutabilis treated cells irrespectively of glucose concentration. This supports an early effect fighting bacteria. Additionally, L. mutabilis prevented bacterial biofilm formation, which is used by bacteria to evade the immune system and antibiotics. In summary, L. mutabilis protects against bacterial infection in uroepithelial cells by preventing adhesion through alteration of the cell surface, increasing antimicrobial peptide expression, and reducing biofilm formation. Together, this promotes bacterial clearance, suggesting that L. mutabilis as extract or as a dietary item can contribute to the prevention of urinary tract infections, which is of importance in an era of increasing antibiotic resistance.
Lupinus mutabilis Extract Exerts an Anti-Diabetic Effect by Improving Insulin Release in Type 2 Diabetic Goto-Kakizaki Rats
(Multidisciplinary Digital Publishing Institute, 2018) Silvia Zambrana; Lena Lundqvist; Orlando Mamani Rodríguez; Sergiu‐Bogdan Catrina; Eduardo Gonzáles; Claes‐Göran Östenson
Lupinus mutabilis (LM) is a legume part of Bolivian traditional diet that has a nutraceutical property reducing blood glucose levels. The prevalence of type 2 diabetes is increasing worldwide thus; the search for novel anti-diabetic drugs is needed. Based on its traditional use, we evaluated the anti-diabetic effect of LM in the spontaneously diabetic Goto-Kakizaki (GK) rat, a model of type 2 diabetes and in Wistar (W) rats as healthy control. LM seeds hydroethanolic extract, analyzed by gas chromatography-mass spectrometry and high-performance liquid chromatography-high resolution mass spectrometry, is a complex mixture of volatile and non-volatile components. A single oral administration of LM extract (2000 mg/kg b.w.) improved glucose tolerance during the oral glucose tolerance test (OGTT) (30⁻120 min) in GK and W rats (p < 0.0001). The long-term treatment with LM (1000 mg/kg b.w.), for 21 days, improved the area under the curve (AUC) of glucose during OGTT at day 20, in both GK (p < 0.01) and W rats (p < 0.01). The HbA1c (GK rats, p < 0.05 and W rats, p < 0.0001) and the non-fasting glucose (GK rats, p < 0.05) were also reduced. LM increased both serum insulin levels (2.4-fold in GK rats and 2.5-fold W rats), and the glucose-induced (16.7 mM glucose) insulin release in isolated islets from treated animals (6.7-fold in GK rats, and 6.6-fold in W rats). Moreover, LM (10 mg/mL) stimulated in vitro glucose induced (16.7 mM glucose) insulin release in batch incubated GK and W rat islets (p < 0.0001). In perifused GK rat islets, insulin release in 16.7 mM glucose was increased 95.3-fold compared to untreated islets (p < 0.0001), while no significant differences were found in perifused W rat islets. The LM mechanism of action, evaluated using inhibitory compounds of the insulin secretion pathway, showed that LM-dependent insulin secretion was reduced 42% by diazoxide (p < 0.001), 70% by nifedipine (p < 0.001), 86.7% by H89 (p < 0.0001), 70.8% by calphostine-C (p < 0.0001) and 93% by pertussis toxin (p < 0.0001). A similar effect was observed in W rats islets. Our findings provide evidence that LM has an anti-diabetic effect through stimulation of insulin release. The effect is-dependent on L-type calcium channel, protein kinase A and C systems, and G protein-coupled exocytosis and is partially mediated by K-ATP channels.
Lupinus mutabilis extract improves insulin secretion in Diabetic Goto-Kakizaki rats
(Georg Thieme Verlag, 2017) Silvia Zambrana; Orlando Mamani Rodríguez; Sergiu‐Bogdan Catrina; Eduardo Gonzáles; C-G Östenson
The prevalence of type 2 diabetes is increasing worldwide and therefore investigation to develop novel therapeutic strategies is needed. Based on the use of Bolivian traditional foods, the aim of this study is to evaluate the anti-diabetic nutraceutical property of Lupinus mutabilis (LM) [1]. The type 2 diabetic model, Goto-Kakizaki rats (GK), was used. In the Oral Glucose Tolerance test (OGTT) LM (2000 mg/kg b.w.), by single oral administration, improved glucose tolerance, expressed by the area under the glucose curve (AUC), 1005.0 ± 57.59mM/120 min vs. placebo 1379.7 ± 132.5 mM/120 min (p < 0.05). The LM long-term treatment (1000 mg/kg b.w.), for 21 days, improved the AUC under the OGTT (827.3 ± 24.80 mM/120 min) vs. value before treatment (1050 ± 26.96 mM/120 min) (p < 0.05). Moreover, LM long-term treatment increased serum insulin levels, after 30 min of glucose challenge, 2.4-fold at day 20 (58.2 ± 2.3µU/ml) vs. GK placebo (24.6 ± 0.8µU/ml) (p < 0.0001). Glycated hemoglobin, HbA1c, was reduced at day 20 by 30% vs. placebo group (p < 0.01). In vitro studies showed that LM (10 mg/ml) stimulates insulin secretion in GK batch incubated islets, at 16.7 mM glucose, 3.3-fold increase (118.9 ± 4.8µU/islets/h vs. 35.1 ± 3.7µU/islet/h, untreated islets) (p < 0.0001). The LM mechanism of action was evaluated using inhibitory compounds of insulin secretion pathway. Insulin secretion of LM (104.7 ± 6.9) was reduced 42% by Diazoxide (60.4 ± 3.2µU/islet/h) (p < 0.001), 70% by calcium-blocker Nifedipine (31.2 ± 3.1µU/islet/h) (p < 0.001), 86.7% by protein kinas A (PKA) blocker, H89 (13.8 ± 1.0µU/islet/h) (p < 0.0001), 70.8% by PKC-blocker Calphostine-C (30.6 ± 1.5µU/islet/h) (p < 0.0001) and 93% by Pertussis toxin, inhibiting insulin exocytosis (7.3 ± 0.9µU/islet/h) (p < 0.0001). Our findings provide evidence of LM anti-diabetic effect explained by stimulation of insulin release, dependent on L-type calcium channels, PKA and PKC system and insulin exocytosis.
Molecular Characterization of Enterotoxigenic Escherichia coli Isolates Recovered from Children with Diarrhea during a 4-Year Period (2007 to 2010) in Bolivia
(American Society for Microbiology, 2013) Lucia Gonzales‐Siles; Samanta Sánchez; Silvia Zambrana; Volga Iñiguez; Gudrun Wiklund; Ann‐Mari Svennerholm; Åsa Sjöling
Enterotoxigenic Escherichia coli (ETEC) is an important cause of childhood diarrhea. This study aimed to characterize ETEC strains isolated from Bolivian children aged <5 years according to enterotoxin profile, colonization factors (CFs), suggested virulence genes, and severity of disease. A total of 299 ETEC isolates recovered from children with diarrhea and 55 ETEC isolates from children without diarrhea (controls) were isolated over a period of 4 years. Strains expressing heat-labile toxin (LT) or heat-stable toxin (ST) alone were about equally common and twice as common as ETEC producing both toxins (20%). ETEC strains expressing human ST (STh) were more common in children aged <2 years, while ETEC strains expressing LT plus STh (LT/STh) were more frequent in 2- to 5-year-old children. Severity of disease was not related to the toxin profile of the strains. CF-positive isolates were more frequently identified in diarrheal samples than in control samples (P = 0.02). The most common CFs were CFA/I and CS14. CFA/I ETEC strains were more frequent in children aged <2 years than CS1+CS3 isolates and CS14 isolates, which were more prevalent in 2- to 5-year-old children. The presence of suggested ETEC virulence genes (clyA, eatA, tia, tibC, leoA, and east-1) was not associated with disease. However, east-1 was associated with LT/STh strains (P < 0.001), eatA with STh strains (P < 0.001), and tia with LT/STh strains (P < 0.001). A minor seasonal peak of ETEC infections was identified in May during the cold-dry season and coincided with the peak of rotavirus infections; this pattern is unusual for ETEC and may be important for vaccination strategies in Bolivia.