Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 20 de 20
Filter
1.
Braz. j. biol ; 83: 1-5, 2023. tab, graf
Article in English | LILACS, VETINDEX | ID: biblio-1468822

ABSTRACT

The essential oil of citronella (Cymbopogon winterianus) has several biological activities, among them the insect repellent action. Some studies showed that cinnamic acid esters can be applied as natural pesticides, insecticides and fungicides. In this context, the objective of the present work was to evaluate the production of esters from citronella essential oil with cinnamic acid via enzymatic esterification. Besides, the essential oil toxicity before and after esterification against Artemia salina and larvicidal action on Aedes aegypti was investigated. Esters were produced using cinnamic acid as the acylating agent and citronella essential oil (3:1) in heptane and 15 wt% NS 88011 enzyme as biocatalysts, at 70 °C and 150 rpm. Conversion rates of citronellyl and geranyl cinnamates were 58.7 and 69.0% for NS 88011, respectively. For the toxicity to Artemia salina LC50 results of 5.29 μg mL-¹ were obtained for the essential oil and 4.36 μg mL-¹ for the esterified oils obtained with NS 88011. In the insecticidal activity against Aedes aegypti larvae, was obtained LC50 of 111.84 μg mL-¹ for the essential oil of citronella and 86.30 μg mL-¹ for the esterified oils obtained with the enzyme NS 88011, indicating high toxicity of the esters. The results demonstrated that the evaluated samples present potential of application as bioinsecticide.


O óleo essencial de citronela (Cymbopogon winterianus) possui diversas atividades biológicas, entre elas a ação repelente a insetos. Alguns estudos mostraram que os ésteres do ácido cinâmico podem ser aplicados como pesticidas naturais, inseticidas e fungicidas. Nesse contexto, o objetivo do presente trabalho foi avaliar a produção de ésteres a partir do óleo essencial de citronela com ácido cinâmico via esterificação enzimática. Além disso, foi investigada a toxicidade do óleo essencial antes e após a esterificação contra Artemia salina e a ação larvicida sobre Aedes aegypti. Os ésteres foram produzidos utilizando ácido cinâmico como agente acilante e óleo essencial de citronela (3: 1) em heptano e 15% em peso da enzima NS 88011 como biocatalisadores, a 70 ° C e 150 rpm. As taxas de conversão de cinamatos de citronelil e geranil foram 58,7 e 69,0% para NS 88011, respectivamente. Para a toxicidade sobre Artemia salina foram obtidos CL50 de 5,29 μg mL-¹ para o óleo essencial e 4,36 μg mL-¹ para os óleos esterificados com NS 88011. Na atividade inseticida contra larvas de Aedes aegypti, obteve-se CL50 de 111,84 μg mL-¹ para o óleo essencial de citronela e 86,30 μg mL-¹ para os óleos esterificados com a enzima NS 88011, indicando alta toxicidade dos ésteres. Os resultados demonstraram que as amostras avaliadas apresentam potencial de aplicação como bioinseticida.


Subject(s)
Animals , Aedes , Artemia , Cymbopogon/enzymology , Cymbopogon/toxicity , Esters/toxicity
2.
Braz. j. biol ; 832023.
Article in English | LILACS-Express | LILACS, VETINDEX | ID: biblio-1469038

ABSTRACT

Abstract The essential oil of citronella (Cymbopogon winterianus) has several biological activities, among them the insect repellent action. Some studies showed that cinnamic acid esters can be applied as natural pesticides, insecticides and fungicides. In this context, the objective of the present work was to evaluate the production of esters from citronella essential oil with cinnamic acid via enzymatic esterification. Besides, the essential oil toxicity before and after esterification against Artemia salina and larvicidal action on Aedes aegypti was investigated. Esters were produced using cinnamic acid as the acylating agent and citronella essential oil (3:1) in heptane and 15 wt% NS 88011 enzyme as biocatalysts, at 70 °C and 150 rpm. Conversion rates of citronellyl and geranyl cinnamates were 58.7 and 69.0% for NS 88011, respectively. For the toxicity to Artemia salina LC50 results of 5.29 g mL-1 were obtained for the essential oil and 4.36 g mL-1 for the esterified oils obtained with NS 88011. In the insecticidal activity against Aedes aegypti larvae, was obtained LC50 of 111.84 g mL-1 for the essential oil of citronella and 86.30 g mL-1 for the esterified oils obtained with the enzyme NS 88011, indicating high toxicity of the esters. The results demonstrated that the evaluated samples present potential of application as bioinsecticide.


Resumo O óleo essencial de citronela (Cymbopogon winterianus) possui diversas atividades biológicas, entre elas a ação repelente a insetos. Alguns estudos mostraram que os ésteres do ácido cinâmico podem ser aplicados como pesticidas naturais, inseticidas e fungicidas. Nesse contexto, o objetivo do presente trabalho foi avaliar a produção de ésteres a partir do óleo essencial de citronela com ácido cinâmico via esterificação enzimática. Além disso, foi investigada a toxicidade do óleo essencial antes e após a esterificação contra Artemia salina e a ação larvicida sobre Aedes aegypti. Os ésteres foram produzidos utilizando ácido cinâmico como agente acilante e óleo essencial de citronela (3: 1) em heptano e 15% em peso da enzima NS 88011 como biocatalisadores, a 70 ° C e 150 rpm. As taxas de conversão de cinamatos de citronelil e geranil foram 58,7 e 69,0% para NS 88011, respectivamente. Para a toxicidade sobre Artemia salina foram obtidos CL50 de 5,29 g mL-1 para o óleo essencial e 4,36 g mL-1 para os óleos esterificados com NS 88011. Na atividade inseticida contra larvas de Aedes aegypti, obteve-se CL50 de 111,84 g mL-1 para o óleo essencial de citronela e 86,30 g mL-1 para os óleos esterificados com a enzima NS 88011, indicando alta toxicidade dos ésteres. Os resultados demonstraram que as amostras avaliadas apresentam potencial de aplicação como bioinseticida.

3.
Braz. j. biol ; 83: e244647, 2023. tab, graf
Article in English | LILACS, VETINDEX | ID: biblio-1278527

ABSTRACT

Abstract The essential oil of citronella (Cymbopogon winterianus) has several biological activities, among them the insect repellent action. Some studies showed that cinnamic acid esters can be applied as natural pesticides, insecticides and fungicides. In this context, the objective of the present work was to evaluate the production of esters from citronella essential oil with cinnamic acid via enzymatic esterification. Besides, the essential oil toxicity before and after esterification against Artemia salina and larvicidal action on Aedes aegypti was investigated. Esters were produced using cinnamic acid as the acylating agent and citronella essential oil (3:1) in heptane and 15 wt% NS 88011 enzyme as biocatalysts, at 70 °C and 150 rpm. Conversion rates of citronellyl and geranyl cinnamates were 58.7 and 69.0% for NS 88011, respectively. For the toxicity to Artemia salina LC50 results of 5.29 μg mL-1 were obtained for the essential oil and 4.36 μg mL-1 for the esterified oils obtained with NS 88011. In the insecticidal activity against Aedes aegypti larvae, was obtained LC50 of 111.84 μg mL-1 for the essential oil of citronella and 86.30 μg mL-1 for the esterified oils obtained with the enzyme NS 88011, indicating high toxicity of the esters. The results demonstrated that the evaluated samples present potential of application as bioinsecticide.


Resumo O óleo essencial de citronela (Cymbopogon winterianus) possui diversas atividades biológicas, entre elas a ação repelente a insetos. Alguns estudos mostraram que os ésteres do ácido cinâmico podem ser aplicados como pesticidas naturais, inseticidas e fungicidas. Nesse contexto, o objetivo do presente trabalho foi avaliar a produção de ésteres a partir do óleo essencial de citronela com ácido cinâmico via esterificação enzimática. Além disso, foi investigada a toxicidade do óleo essencial antes e após a esterificação contra Artemia salina e a ação larvicida sobre Aedes aegypti. Os ésteres foram produzidos utilizando ácido cinâmico como agente acilante e óleo essencial de citronela (3: 1) em heptano e 15% em peso da enzima NS 88011 como biocatalisadores, a 70 ° C e 150 rpm. As taxas de conversão de cinamatos de citronelil e geranil foram 58,7 e 69,0% para NS 88011, respectivamente. Para a toxicidade sobre Artemia salina foram obtidos CL50 de 5,29 μg mL-1 para o óleo essencial e 4,36 μg mL-1 para os óleos esterificados com NS 88011. Na atividade inseticida contra larvas de Aedes aegypti, obteve-se CL50 de 111,84 μg mL-1 para o óleo essencial de citronela e 86,30 μg mL-1 para os óleos esterificados com a enzima NS 88011, indicando alta toxicidade dos ésteres. Os resultados demonstraram que as amostras avaliadas apresentam potencial de aplicação como bioinseticida.


Subject(s)
Animals , Oils, Volatile/toxicity , Aedes , Cymbopogon , Insect Repellents , Insecticides/toxicity , Esterification , Larva
4.
Braz J Biol ; 83: e244647, 2021.
Article in English | MEDLINE | ID: mdl-34190758

ABSTRACT

The essential oil of citronella (Cymbopogon winterianus) has several biological activities, among them the insect repellent action. Some studies showed that cinnamic acid esters can be applied as natural pesticides, insecticides and fungicides. In this context, the objective of the present work was to evaluate the production of esters from citronella essential oil with cinnamic acid via enzymatic esterification. Besides, the essential oil toxicity before and after esterification against Artemia salina and larvicidal action on Aedes aegypti was investigated. Esters were produced using cinnamic acid as the acylating agent and citronella essential oil (3:1) in heptane and 15 wt% NS 88011 enzyme as biocatalysts, at 70 °C and 150 rpm. Conversion rates of citronellyl and geranyl cinnamates were 58.7 and 69.0% for NS 88011, respectively. For the toxicity to Artemia salina LC50 results of 5.29 µg mL-1 were obtained for the essential oil and 4.36 µg mL-1 for the esterified oils obtained with NS 88011. In the insecticidal activity against Aedes aegypti larvae, was obtained LC50 of 111.84 µg mL-1 for the essential oil of citronella and 86.30 µg mL-1 for the esterified oils obtained with the enzyme NS 88011, indicating high toxicity of the esters. The results demonstrated that the evaluated samples present potential of application as bioinsecticide.


Subject(s)
Aedes , Cymbopogon , Insect Repellents , Insecticides , Oils, Volatile , Animals , Esterification , Insecticides/toxicity , Larva , Oils, Volatile/toxicity
5.
Science ; 372(6548): 1314-1318, 2021 06 18.
Article in English | MEDLINE | ID: mdl-34016741

ABSTRACT

In heterogeneous catalysis research, the reactivity of individual nanofacets of single particles is typically not resolved. We applied in situ field electron microscopy to the apex of a curved rhodium crystal (radius of 650 nanometers), providing high spatial (~2 nanometers) and time resolution (~2 milliseconds) of oscillatory catalytic hydrogen oxidation, to image adsorbed species and reaction fronts on the individual facets. Using ionized water as the imaging species, the active sites were directly imaged with field ion microscopy. The catalytic behavior of differently structured nanofacets and the extent of coupling between them were monitored individually. We observed limited interfacet coupling, entrainment, frequency locking, and reconstruction-induced collapse of spatial coupling. The experimental results are backed up by microkinetic modeling of time-dependent oxygen species coverages and oscillation frequencies.

6.
Chemosphere ; 213: 41-52, 2018 Dec.
Article in English | MEDLINE | ID: mdl-30212718

ABSTRACT

The adverse effect of gold-based nanoparticles is still an open question since it depends on several factors as shape, surface charge or route of administration. In this study, we investigated the influence of shape and human serum albumin (HSA) coating on the adverse effects of spherical (AuNP) and nanorods (AuNR) gold-based particles. F C3H (fibroblast) and HTC (hepatocellular carcinoma) cell lines both from liver were exposed to 25, 75 and 125 µg mL-1, which correspond to 109 NP mL-1. For in vivo studies, Wistar rats received these materials by oral administration in doses of 10 µg kg-1 or 40 µg kg-1. Systemic toxicity was verified after 24 h and 48 h by morphological analysis, blood parameters and myeloperoxidase enzyme activity. Our results revealed that HSA corona does not influence totally the pathway of interactions between AuNP and AuNR. In vitro results evidenced that AuNP can decrease in at least 50% viability of F C3H and cell adhesion of HTC, but corona significantly overcomes these effects. No differences between shape or corona were observed in function of cell lines. In vivo studies showed that 40 µg kg-1 of AuNP-HSA caused an enhancement of the myeloperoxidase response indicating inflammatory processes. An increase from 40% to 80% on alkaline phosphatase levels were found for all groups. Our findings suggested that gold-based particles coated or not with HSA do not cause expressive adverse effects on in vitro or in vivo systems, and their oral administration cannot cause a systemic effect in the experimental conditions used here.


Subject(s)
Gold/chemistry , Nanospheres/chemistry , Nanotubes/chemistry , Theranostic Nanomedicine/methods , Animals , Humans , Rats , Rats, Wistar
7.
RSC Adv ; 8(16): 8856-8869, 2018 Feb 23.
Article in English | MEDLINE | ID: mdl-35539825

ABSTRACT

Experimental results are presented here obtained by a drop calorimetric method, in which Ni and Cu particles, both in bulk and nanosized form, were dropped into a liquid Sn-3.8Ag-0.7Cu solder alloy (in wt%). The molar enthalpies of mixing of the liquid (Sn-3.8Ag-0.7Cu)-Ni(Cu) alloys were measured. An extra exothermic heat effect is observed when dropping nano-particles instead of macro-particles. This is partly due to the loss of the large surface area and the corresponding large surface enthalpy of the nano-particles before their dissolution in the liquid alloy. However, a large additional exothermic heat effect was also found in the case of Cu-nano-particles, due to the exchange chemical reaction between the Cu2O shell of the nano-particles and liquid Sn; this is caused by the fact that the Cu-nano-particles are core-shell particles with an inner metallic Cu core and an outer Cu2O shell. This effect is less significant for Ni nano-particles which have a thinner oxide shell.

8.
Dalton Trans ; 46(27): 8855-8860, 2017 Jul 11.
Article in English | MEDLINE | ID: mdl-28443884

ABSTRACT

Macroporous magnesium silicide monoliths were successfully prepared by a two-step synthesis procedure. The reaction of gaseous magnesium vapor with macro-/mesoporous silicon, which was generated from hierarchically organized meso-/macroporous silica by a magnesiothermic reduction reaction, resulted in monolithic magnesium silicide with a cellular, open macroporous structure. By adjusting the reaction conditions, such as experimental set-up, temperature and time, challenges namely loss of porosity or phase purity of Mg2Si were addressed and monolithic magnesium silicide with a cellular network builtup was obtained.

9.
J Dev Orig Health Dis ; 7(4): 391-407, 2016 08.
Article in English | MEDLINE | ID: mdl-27168118

ABSTRACT

UNLABELLED: The hypertensive disorders of pregnancy complicate up to 10% of pregnancies worldwide and are a leading cause of maternal, foetal, and neonatal morbidity and mortality. The aim of this study was to present an overview of recent studies addressing offspring's medium and long-term health outcomes after intrauterine exposure to maternal hypertension. A search on PubMed/MEDLINE and Bireme databases was conducted to identify observational studies that reported any offspring outcome measured after the 6th month of life. The search was limited to studies published after May 2008. Forty-five articles were included and categorized into four groups of outcomes: cardiovascular, immune, metabolic and behavioural/neurological effects. According to our findings, hypertensive disorders of pregnancy had an overall negative impact on offspring's cardiovascular, immune and neurological health, although not all parameters analysed in each group had consistent results among studies. The most prominent and reliable associations were verified between gestational hypertension and higher offspring's blood pressure and between preeclampsia and offspring's lower cognitive functioning. In the metabolic outcomes, body composition had conflicting results among papers, while all studies that examined blood biomarkers showed no evidence that preeclampsia or gestational hypertension could be associated with an alteration of this metabolic outcomes. Most included studies were highly heterogeneous regarding the measure of outcomes and covariables used for adjustments. Future studies should consider using the same protocols and cut-off points already published so that results can be better compared and summarized. This review was registered in PROSPERO. REGISTRATION NUMBER: CRD42015020838.


Subject(s)
Cardiovascular Diseases/etiology , Cognition Disorders/etiology , Hypertension, Pregnancy-Induced/physiopathology , Metabolic Diseases/etiology , Cardiovascular Diseases/pathology , Cognition Disorders/pathology , Female , Humans , Infant, Newborn , Metabolic Diseases/pathology , Pregnancy
10.
Catal Letters ; 146(10): 1867-1874, 2016.
Article in English | MEDLINE | ID: mdl-32355436

ABSTRACT

ABSTRACT: The catalytic H2 oxidation reaction on stepped Rh surfaces in the 10-6 mbar pressure range was studied in situ on individual high-Miller-index domains of a polycrystalline Rh foil by PEEM (photoemission electron microscopy) and on a Rh nanotip by FIM/FEM (field-ion/field-emission microscopy). The activity, particularly the tolerance to poisoning by oxygen, was found to strongly depend on the density of steps and defects, as well as on the size of the catalytically active surfaces.

12.
Clin. transl. oncol. (Print) ; 12(10): 704-706, oct. 2010. ilus
Article in English | IBECS | ID: ibc-124361

ABSTRACT

Breast tumors in adolescents are very rare and mostly benign. Fibroadenomas are the most frequent, but within the extensive differential diagnosis, the phyllodes tumor must be mentioned, which accounts for about 1% of breast tumors and the diagnosis of which is very rare in patients younger than 20 years. There are no specific symptoms or radiological images to distinguish phyllodes tumor from fibroadenoma; therefore, histological examination is mandatory for diagnosis. Histology also allows the classification of phyllodes tumor into benign, borderline, or malignant types for appropriate surgical treatment: freemargin excision in benign tumors and mastectomy in the other two types. Fortunately, the majority of these tumors are benign, and treatment maximizes breast conservation with free infiltration margins surgery, given that this fact is the most important factor to prevent local recurrence. In this article, we describe a rare case of borderline cystosarcoma phyllodes in a 12-year-old girl (AU)


Subject(s)
Humans , Female , Child , Breast Neoplasms/pathology , Breast Neoplasms/surgery , Mastectomy/methods , Mastectomy , Phyllodes Tumor/surgery
13.
J Nutr Health Aging ; 14(4): 266-70, 2010 Apr.
Article in English | MEDLINE | ID: mdl-20305992

ABSTRACT

OBJECTIVE: The objective of this study was to identify the nutritional status of hospitalized elderly and verify if calf circumference can be a tool to monitor nutritional status in this population. METHODS: A total of 170 inpatients (79 men and 91 women) aged more than 60 years were assessed. Anthropometric and dietary assessments were done according to standard procedures. The software STATISTICA 6.0 was used for the statistical analysis. The confidence interval was set at 95% and significance level at 5% (p < 0.05). RESULTS: Body mass index assessment revealed a high rate of underweight patients (45.3%), and arm circumference and triceps skinfold revealed a high prevalence of depletion. Males had more lean mass according to the mid-arm muscle circumference (p=0.017) and mid-arm muscle area (p=0.01), and females presented higher triceps skinfold values (p < 0.001). There was a positive correlation between calf circumference and Body Mass Index (p < 0.001), arm circumference (p=0.001), triceps skinfold (p=0.001), mid-arm muscle circumference (p=0.001), and mid-arm muscle area (p=0.001). CONCLUSION: This study found a positive correlation between calf circumference and nutritional status of assessed patients indicating that this measurement can be used as a complementary tool for monitoring the nutritional status of elderly inpatients.


Subject(s)
Anthropometry/methods , Leg/anatomy & histology , Muscle, Skeletal/anatomy & histology , Nutrition Assessment , Nutritional Status , Thinness/epidemiology , Age Factors , Aged , Aged, 80 and over , Arm/anatomy & histology , Body Composition , Body Mass Index , Female , Hospitalization , Humans , Inpatients , Male , Middle Aged , Prevalence , Skinfold Thickness
14.
Acta Paediatr ; 99(6): 934-9, 2010 Jun.
Article in English | MEDLINE | ID: mdl-20003103

ABSTRACT

AIM: We studied the effect on neurodevelopment of infants who are exposed to thimerosal in tetanus-diphtheria (Td) vaccines during pregnancy. METHODS: We compared Gesell Developmental Schedules (GDS) of exclusive breastfed infants at 6 months born to mothers who received Td (1 to 3 doses) against those who were born to mothers who did not take such vaccines. RESULTS: Compared with the group of infants not exposed to ethylmercury in utero, the infants of exposed mothers showed no significant difference in neurodevelopment delays. Although there was a significant correlation between hair-Hg of mothers and hair-Hg of neonates (Spearman r = 0.353; p = 0.0011), there was no significant correlation between the level of in utero exposure to ethylmercury in Td vaccines and neonate's hair-Hg concentrations (Spearman r = 0.060; p = 0.5922). However, regression analysis showed that GDS at 6 months was significantly associated with total mercury concentration of neonate's hair but was not sensitive to the number of vaccines taken by the mother. CONCLUSION: Early neurodevelopment of exclusively breastfed infants is sensitive to in utero exposure to mercury, but maternal thimerosal exposure in tetanus-diphtheria vaccines per se cannot portend clinical neurodevelopment delays measured by GDS at 6 months.


Subject(s)
Developmental Disabilities/chemically induced , Prenatal Exposure Delayed Effects , Preservatives, Pharmaceutical/adverse effects , Thimerosal/adverse effects , Adolescent , Adult , Breast Feeding , Diphtheria Toxoid/adverse effects , Female , Hair/chemistry , Humans , Infant , Middle Aged , Neuropsychological Tests , Pregnancy , Regression Analysis , Tetanus Toxoid/adverse effects , Thimerosal/analysis , Young Adult
15.
In Vitro Cell Dev Biol Anim ; 39(3-4): 124-30, 2003.
Article in English | MEDLINE | ID: mdl-14505435

ABSTRACT

We have tested amplified fragment length polymorphism (AFLP) technology, in comparison with isoenzyme analysis, for the simultaneous detection of inter- and intraspecific cell line cross-contaminations (CCCs) in the cell line collection held at the Istituto Zooprofilattico della Lombardia e dell'Emilia Romagna. Isoenzyme analysis identified four cases of interspecific CCCs. In a single experiment, AFLP was able to identify the species of origin of all cell lines for which a reference genomic deoxyribonucleic acid was available and to detect five interspecific contaminations. Four CCCs confirmed data on isoenzymes, whereas the fifth CCC was detected in a species for which isoenzyme analysis was noninformative. In addition, AFLP was able to identify the putative source of the contaminations detected. The utility of the technology in the detection of intraspecific cell line contaminations depends on the number of cell lines that have to be distinguished in a specific species and on the availability of highly informative fingerprinting systems. In mice, a single AFLP primer pair produced 16 polymorphisms and distinguished all the 15 strains of mouse cell lines analyzed. In humans, 18 AFLPs identified 83 different profiles in the 159 cell lines analyzed. Amplified fragment length polymorphism can conveniently be applied for cell line fingerprinting in species for which hypervariable markers are not available. In species for which a highly informative multiplex of microsatellite markers is available, AFLP can still provide a useful and cheap tool for simultaneously testing inter- and intraspecific contaminations.


Subject(s)
DNA Fingerprinting , Polymorphism, Genetic/genetics , Polymorphism, Restriction Fragment Length , Animals , Cell Culture Techniques/methods , Cell Line , Gene Amplification , Gene Expression Profiling , Humans , Isoenzymes/genetics , Mice/genetics
16.
Pediatr Nephrol ; 16(7): 594-7, 2001 Jul.
Article in English | MEDLINE | ID: mdl-11465810

ABSTRACT

The case of a 12-year-old boy who developed polyuria and polydipsia while on amphotericin B treatment is discussed. The clinical and laboratory features are most consistent with partial nephrogenic diabetes insipidus. Several adult patients have been reported with amphotericin B-induced nephrogenic diabetes insipidus. To the knowledge of the authors, this is the first pediatric patient described with this condition. Pharmacological doses of antidiuretic hormone in conjunction with diuretic treatment significantly reduced the polyuria and alleviated the associated symptoms. The authors propose that in amphotericin B-induced partial nephrogenic diabetes insipidus, pharmacological doses of antidiuretic hormone may offer an additional benefit to commonly used diuretic therapy.


Subject(s)
Amphotericin B/adverse effects , Antifungal Agents/adverse effects , Diabetes Insipidus, Nephrogenic/chemically induced , Amphotericin B/therapeutic use , Antifungal Agents/therapeutic use , Aspergillosis/drug therapy , Child , Diabetes Insipidus, Nephrogenic/drug therapy , Diabetes Insipidus, Nephrogenic/pathology , Humans , Male , Renal Agents/therapeutic use , Vasopressins/therapeutic use
SELECTION OF CITATIONS
SEARCH DETAIL
...