RESUMO
BACKGROUND: Cancer in older patient favours the development of frailty: feeling of exhaustion, loss of weight, decreased muscle strength, slow gait speed, and low physical activity. OBJECTIVES: To evaluate the efficacy of adapted physical activity phone advices in limiting the cancer-induced loss of autonomy and frailty phenotype development. DESIGN: Multicenter randomized controlled trial. SETTING: Patients (>70y) undergoing curative treatment for cancer (n=400) will be recruited from 12 centres. INTERVENTION: The intervention consists in phoned personalized physical activity advices related to strength, aerobic, balance, proprioception, and flexibility. The contacts are performed twice a month during six months and then monthly until 1 year. The intervention complements the PNNS booklet advices (National Nutritional Health Program). The trial compares «individualized phone advices + PNNS¼ to «usual care + PNNS¼. MEASUREMENTS: Functional, cognitive, clinical and self-reported data are assessed before treatment and at 3, 6, 12, 18, and 24 month follow-up. The primary outcome is the proportion of subjects with a one-year decreased SPPB (Short Physical Performance Battery) score of one point or more, as compared to baseline. The secondary outcomes include quality of life items, rate of hospitalizations, institutionalizations, mortality, Fried phenotype at 1 and 2 years, and the SPPB score at 2 years. DISCUSSION: This large trial will provide clinical data of the effects of an exercise advices intervention in older patients during cancer therapy on function and cognition evolution, and quality of life. The possibilities of minimizing the development of frailty phenotype due to these advices will be explored.
RESUMO
Skin surface enzyme activities were found to be significantly different in healthy and in skin with atopic dermatitis and, following appropriate treatment, a close correlation was observed between the clinical staging of the atopic dermatitis and the levels of the assayed marker enzymes. Samples were taken, by stripping with simple adhesive tapes, from a group of subjects on cure in a spa. The corneocytes were recovered from the first layers of the stratum corneum. Aqueous extracts of the strips were tested for their activity on chromophoric substrates which allow fluorescence spectrometry to be used to assay the trypsin-like, acid-phosphatase-like and phospholipase-A2-like activities. We show that the restoration of return to activities close to those of healthy subjects is related to the general condition of the patients, who showed a clearly improved SCORAD. Recovery of the trypsin-like activity and attenuation of the phospholipase-like activity, paralleled the regression of the dermatitis as assessed by a decrease in clinically evaluated parameters of xerosis and inflammation.
Assuntos
Dermatite Atópica/enzimologia , Enzimas/metabolismo , Fosfatase Ácida/metabolismo , Adolescente , Adulto , Biomarcadores/análise , Criança , Dermatite Atópica/fisiopatologia , Dermatite Atópica/terapia , Feminino , Humanos , Masculino , Fosfolipases A/metabolismo , Fosfolipases A2 , Estatísticas não Paramétricas , Tripsina/metabolismoRESUMO
The peroxynitrite anion is a potent oxidizing agent, formed by the diffusion-limited combination of nitric oxide and superoxide, and its production under physiological conditions is associated with the pathologies of a number of inflammatory and neurodegenerative diseases. Nitration of Escherichia coli iron superoxide dismutase (Fe-SOD) by peroxynitrite was investigated, and demonstrated by spectral changes and electrospray mass spectroscopic analysis. HPLC and mass studies of the tryptic digests of the mono-nitrated Fe-SOD indicated that tyrosine-34 was the residue most susceptible to nitration by peroxynitrite. Exclusive nitration of this residue occurred when Fe-SOD was exposed to a cumulative dose of 0.4 mM peroxynitrite. Unlike with human Mn-SOD, this single modification did not inactivate E. coli Fe-SOD at pH 7.4. When Fe-SOD was exposed to higher concentrations of peroxynitrite (7 mM), eight tyrosine residues per subunit of the protein, of the nine available, were nitrated without loss of catalytic activity of the enzyme. The pK(a) of nitrated tyrosine-34 was determined to be 7.95+/-0.15, indicating that the peroxynitrite-modified enzyme appreciably maintains its protonation state under physiological conditions.
Assuntos
Escherichia coli/enzimologia , Ácido Peroxinitroso/farmacologia , Superóxido Dismutase/metabolismo , Tirosina , Sequência de Aminoácidos , Isoenzimas/metabolismo , Cinética , Dados de Sequência Molecular , Fragmentos de Peptídeos/química , Conformação Proteica , Espectrometria de Massas por Ionização por Electrospray , Superóxido Dismutase/químicaRESUMO
Glycolysis is perceived as a promising target for new drugs against parasitic trypanosomatid protozoa because this pathway plays an essential role in their ATP supply. Trypanosomatid glycolysis is unique in that it is compartmentalized, and many of its enzymes display unique structural and kinetic features. Structure- and catalytic mechanism-based approaches are applied to design compounds that inhibit the glycolytic enzymes of the parasites without affecting the corresponding proteins of the human host. For some trypanosomatid enzymes, potent and selective inhibitors have already been developed that affect only the growth of cultured trypanosomatids, and not mammalian cells.
Assuntos
Glicólise/efeitos dos fármacos , Isomerases/metabolismo , Leishmania , Fosfotransferases/metabolismo , Tripanossomicidas/farmacologia , Trypanosoma brucei brucei , Animais , Inibidores Enzimáticos/farmacologia , Humanos , Isomerases/antagonistas & inibidores , Leishmania/efeitos dos fármacos , Leishmania/enzimologia , Fosfotransferases/antagonistas & inibidores , Trypanosoma brucei brucei/efeitos dos fármacos , Trypanosoma brucei brucei/enzimologiaRESUMO
Various phosphono-phosphates and diphosphonates were synthesized as 1,3-diphosphoglycerate (1,3-diPG) analogues by using a beta-ketophosphonate, an alpha-fluoro,beta-ketophosphonate or a beta-ketophosphoramidate to mimic the unstable carboxyphosphate part of the natural substrate. The inhibitory effect of these analogues on glyceraldehyde-3-phosphate dehydrogenases (GAPDH) from Trypanosoma brucei (Tb) and rabbit muscle were measured with respect to both substrates, glyceraldehyde-3-phosphate (GAP) and 1,3-diPG. Interestingly, all 1,5-diphosphono,2-oxopentanes without substitution at the C-3 position selectively inhibit the Tb GAPDH with respect to 1,3-diPG and are without effect on Rm GAPDH. All 1-phospho,3-oxo,4-phosphonobutanes show themselves to be non-selective inhibitors either with regard to substrates or organisms, but they will be of a great interest as 1,3-diPG stable models for structural studies of co-crystals with GAPDHs.
Assuntos
Ácidos Difosfoglicéricos/farmacologia , Inibidores Enzimáticos/farmacologia , Gliceraldeído-3-Fosfato Desidrogenases/antagonistas & inibidores , Tripanossomicidas/síntese química , Tripanossomicidas/farmacologia , Trypanosoma brucei brucei/enzimologia , Animais , Ácidos Difosfoglicéricos/síntese química , Inibidores Enzimáticos/síntese química , Gliceraldeído-3-Fosfato Desidrogenases/metabolismo , Concentração Inibidora 50 , Músculos/enzimologia , Coelhos , Relação Estrutura-AtividadeRESUMO
New compounds have been synthesized based on the structure of the anti-tumoral drug tamoxifen and its diphenylmethane derivative, N,N-diethyl-2-[(4-phenyl-methyl)-phenoxy]-ethanamine, HCl (DPPE). These new compounds have no affinity for the estrogen receptor (ER) and bind with various affinity to the anti-estrogen binding site (AEBS). Compounds 2, 10, 12, 13, 20a, 20b, 23a, 23b, 29 exhibited 1.1-69.5 higher affinity than DPPE, and compounds 23a and 23b have 1.2 and 3.5 higher affinity than tamoxifen. Three-dimensional structure analysis, performed using the intersection of the van der Waals volume occupied by tamoxifen in its crystallographic state and the van der Waals volume of these new compounds in their calculated minimal energy conformation, correlated well with their pKi for AEBS (r = 0.84, P<0.0001, n = 18). This is the first structure-affinity relationship (SAR) ever reported for AEBS ligands. Moreover in this study we have reported the synthesis of new compounds of higher affinity than the lead compounds and that are highly specific for AEBS. Since these compounds do not bind ER they will be helpful to study AEBS mediated cytotoxicity. Moreover our study shows that our strategy is a new useful guide to design high affinity and selective ligands for AEBS.
Assuntos
Microssomos/metabolismo , Éteres Fenílicos/química , Receptores de Droga/metabolismo , Moduladores Seletivos de Receptor Estrogênico/química , Moduladores Seletivos de Receptor Estrogênico/síntese química , Tamoxifeno/análogos & derivados , Animais , Sítios de Ligação , Humanos , Ligantes , Espectroscopia de Ressonância Magnética , Modelos Moleculares , Estrutura Molecular , Éteres Fenílicos/metabolismo , Ensaio Radioligante , Ratos , Receptores de Droga/química , Moduladores Seletivos de Receptor Estrogênico/metabolismo , Relação Estrutura-Atividade , Tamoxifeno/química , Tamoxifeno/metabolismoRESUMO
A series of S-nitrosothiols, structurally related to the NO*-donor S-nitroso-N-acetylpenicillamine, and of organic nitrate esters that contain amidine groups which specify a recognition via the trypanosomal purine transporter P2, were synthesized and tested for their ability to inhibit the uptake of [2-(3)H]adenosine on Trypanosoma equiperdum.
Assuntos
Proteínas de Transporte/metabolismo , Proteínas de Membrana/metabolismo , Doadores de Óxido Nítrico/síntese química , Nucleosídeos de Purina/metabolismo , Trypanosoma/metabolismo , Animais , Transporte Biológico , Doadores de Óxido Nítrico/metabolismo , Proteínas de Transporte de NucleosídeosRESUMO
Various D-fructose analogues modified at C-1 or C-6 positions were synthesized from D-glucose by taking advantage of the Amadori rearrangement or using the aldol condensation between dihydroxyacetone phosphate and appropriate aldehyde catalyzed by fructose 1,6-diphosphate aldolase from rabbit muscle. The affinities of the analogues for the glucose transporter expressed in the mammalian form of Trypanosoma brucei were determined by inhibition of radiolabelled 2-deoxy-D-glucose (2-DOG) transport using zero-trans kinetic analysis. Interestingly, the analogues bearing an aromatic group (i.e. a fluorescence marker) at C-1 or C-6 positions present comparable apparent affinities to D-fructose for the transporter. This result could find applications for hexose transport studies and also provides criteria for the design of glucose import inhibitors.
Assuntos
Frutose/análogos & derivados , Frutose/síntese química , Proteínas de Transporte de Monossacarídeos/metabolismo , Trypanosoma brucei brucei/metabolismo , Animais , Transporte Biológico , Espectroscopia de Ressonância Magnética , Espectrometria de Massas , Sondas Moleculares , Músculos/enzimologia , CoelhosRESUMO
The pharmacokinetics of megazol (2-amino-5-(1-methyl-5-nitro-2-imidazolyl)-1,3,4-thiadiazol, CAS 19622-55-0) was investigated after a 100 mg/kg oral administration to six primates infected with Trypanosoma brucei gambiense. The plasma levels of megazol were between 0.2 microgram/ml and 46 micrograms/ml 24 h after dosing in all animals. In animals with prolonged infection, megazol absorption was accelerated (Tmax was 4 h compared with 8 h, for day 53 and day 39 post inoculation) but the amount absorbed was not modified. The megazol concentrations in the cerebrospinal fluid represented between 5.5% and 10.6% of the plasma levels at the same times. Unchanged megazol was eliminated predominantly via the kidneys: 46-96% of the ingested dose was recovered in the urine, compared with 0-5% in the faeces. Furthermore, this urinary elimination of megazol was altered in animals with prolonged infections. In the urine, 4 unknown metabolites were observed, unchanged megazol was characterized by LC-MS/MS. This study indicates that megazol crosses the blood-brain barrier after oral administration. Prolonged infections affect the absorption of megazol and its urinary elimination.
Assuntos
Tiadiazóis/farmacocinética , Tripanossomicidas/farmacocinética , Trypanosoma brucei gambiense , Tripanossomíase Africana/metabolismo , Animais , Área Sob a Curva , Barreira Hematoencefálica , Chlorocebus aethiops , Cromatografia Líquida de Alta Pressão , Fezes/química , Feminino , Meia-Vida , Masculino , Tiadiazóis/metabolismo , Tripanossomicidas/metabolismo , Tripanossomíase Africana/parasitologiaRESUMO
Megazol, CL 64,855 (2-amino-5-[1-methyl-5-nitro-2-imidazolyl]-1,3, 4-thiazole) has been shown to be extremely effective in clearing experimental infections of African trypanosomes. An unusual amino-purine transporter termed P2, implicated in the transport of both the diamidine and melaminophenyl arsenical classes of drug in Trypanosoma brucei, recognised chemical groups on compounds which are also present on megazol. Megazol interacted with this carrier protein, as judged by its ability to inhibit P2 adenosine transport and to abrogate in vitro arsenical-induced lysis in a dose-dependent manner. However, parasites resistant to melaminophenyl arsenical and diamidine drugs due to lack of the P2 transporter showed no resistance to megazol. This is because passive diffusion represented the major route of entry. Initial rates of uptake were not saturable within the limit of megazol's solubility and did not conform to thermodynamic precepts compatible with carrier-mediated uptake. Adenosine and other P2 transporter substrates, even at high concentration, had little impact on megazol uptake. Uptake was biphasic, with a very rapid equilibration across the membrane followed by a slower accumulation over time. The equilibration phase represented a simple passive diffusion, with the subsequent uptake probably being due to metabolism of the drug.
Assuntos
Nitroimidazóis/metabolismo , Tiadiazóis/metabolismo , Tripanossomicidas/metabolismo , Trypanosoma brucei brucei/metabolismo , África , Animais , Transporte Biológico , Interações Medicamentosas , Resistência a Medicamentos , Nucleosídeos/farmacologia , Receptores Purinérgicos P2/efeitos dos fármacos , Temperatura , Fatores de Tempo , Tripanossomíase Africana/metabolismoRESUMO
Nitric oxide (NO.) has been identified as a principal regulatory molecule of the immune system and the major cytotoxic mediator of activated immune cells. NO. can also react rapidly with a variety of biological species, particularly with the superoxide radical anion O2.- at almost diffusion-limited rates to form peroxynitrite anion (ONOO-). ONOO- and its proton-catalyzed decomposition products are capable of oxidizing a great diversity of biomolecules and can act as a source of toxic hydroxyl radicals. As a consequence, a strategy for the development of molecules with potential trypanocidal activities could be developed to increase the concentration of nitric oxide in the parasites through NO.-releasing compounds. In this way, the rate of formation of peroxynitrite from NO. and O2.- would be faster than the rate of dismutation of superoxide radicals by superoxide dismutases which constitute the primary antioxidant enzymatic defense system in trypanosomes. The adenosine transport systems of parasitic protozoa, which are also in certain cases implicated in the selective uptake of active drugs such as melarsoprol or pentamidine, could be exploited to specifically target these NO.-releasing compounds inside the parasites. In this work, we present the synthesis, characterization and biological evaluation of a series of molecules that contain both a group which would specifically target these drugs inside the parasites via the purine transporter, and an NO.-donor group that would exert a specific pharmacological effect by increasing NO level, and thus the peroxynitrite concentration inside the parasite.
Assuntos
Proteínas de Transporte/efeitos dos fármacos , Proteínas de Membrana/efeitos dos fármacos , Nitratos/síntese química , Doadores de Óxido Nítrico/síntese química , Óxido Nítrico/metabolismo , Trypanosoma/metabolismo , Adenosina/farmacocinética , Animais , Proteínas de Transporte/metabolismo , Proteínas de Membrana/metabolismo , Doadores de Óxido Nítrico/farmacocinética , Proteínas de Transporte de Nucleosídeos , Trypanosoma/efeitos dos fármacosRESUMO
The present paper describes the synthetic routes of six phosphono analogues of dihydroxyacetone phosphate and five phosphono analogues of glyceraldehyde 3-phosphate through alpha-, beta- and gamma-hydroxyphosphonate esters precursors containing a protected carbonyl group. In some situations, depending on the sequence used for the deprotection of the phosphonate and carbonyl groups, the aldol/ketol rearrangement allowed the synthesis of either dihydroxyacetone phosphate or glyceraldehyde 3-phosphate analogues from the same precursors. All these analogues are of interest both as active-site probes and as potential substrates for glycolytic enzymes such as fructose 1,6-diphosphate aldolases (EC 4.1.2.13).
Assuntos
Fosfato de Di-Hidroxiacetona/análogos & derivados , Fosfato de Di-Hidroxiacetona/química , Gliceraldeído 3-Fosfato/análogos & derivados , Gliceraldeído 3-Fosfato/química , Animais , Fosfato de Di-Hidroxiacetona/metabolismo , Frutose-Bifosfato Aldolase/metabolismo , Gliceraldeído 3-Fosfato/metabolismo , Músculo Esquelético/enzimologia , Organofosfonatos/química , Coelhos , Especificidade por SubstratoRESUMO
1-Amino-2,5-anhydro-1-deoxy-D-mannitol and a series of arylamino derivatives were prepared by nitrous acid deamination of 2-amino-2-deoxy-D-glucose and subsequent reductive amination of the resulting 2,5-anhydro-D-mannose. Some of these compounds showed an enhanced affinity for the hexose transporter of Trypanosoma brucei as compared to D-fructose.
Assuntos
Manitol/análogos & derivados , Animais , Sequência de Carboidratos , Cinética , Manitol/síntese química , Dados de Sequência Molecular , Proteínas de Transporte de Monossacarídeos/metabolismo , Trypanosoma brucei brucei/químicaRESUMO
OBJECTIVE: The activity of prehospital emergency medicine (PEM) teams is mainly assessed by the amount of medical interventions and their duration. However, these two parameters do not reflect workload correctly. The aim of this study was to compare a new activity scoring system for PEM teams (CAS) with the standard TISS score. STUDY DESIGN: Prospective comparative study. PATIENTS: This study included 4,650 patients, with a median age of 39 years [0-100], attended by PEM teams during 4,189 ambulance transports (83% primary transports and 17% interhospital transfers). METHODS: The CAS score derived from Omega scoring system is the sum of 51 items specifically suited for PEM, each one being rated 1, 3, 6 or 10. CAS and TISS, were prospectively determined for all medical ambulance transports over 1.5 year. Transport data and main diagnosis were collected. Results were analysed with non parametric statistical tests. RESULTS: Median duration of interventions (39 min [0-475]) and median CAS score (7 [0-72]) were comparable (R' = 0.38, P < 0.001). Median TISS was 3 [0-30]. CAS score was correlated with TISS (R' = 0.92, P < 0.001). CAS score was higher in men than in women (7 [0-72] vs 7 [0-45], P < 0.001). CAS scores in patients with cardiologic (11 [0-72]), respiratory (9 [0-31]) or neurological insults (9 [0-43]) were significantly higher than those of patients with other insults (P < 0.001). CONCLUSION: The CAS scoring system is a valuable indicator of medical team prehospital workload, probably more suited for prehospital emergency medicine than TISS.
Assuntos
Ambulâncias/normas , Serviços Médicos de Emergência/normas , Auxiliares de Emergência/normas , Feminino , França , Humanos , Masculino , Estudos Prospectivos , Controle de Qualidade , Análise de Regressão , Fatores Sexuais , Transporte de Pacientes/normas , Transporte de Pacientes/estatística & dados numéricosRESUMO
Em 1968, um composto do tipo 5-nitroimidazol, o megazol, foi sintetizado por Berkelhammer e Asato e demonstrou largo espectro de ação biológica. Em 1980, pesquisadores brasileiros determinaram excelente atividade desta molécula contra o Trypanosoma cruzi em ratos. Constam da literatura somente três rotas para obtenção deste fármaco, que podem ser otimizadas no tocante ao aumento da produtividade e minimizacao dos riscos. A nova rota, ora proposta, é uma alternativa para a síntese do megazol e abre caminhos para obtenção de seus análogos estruturais
Assuntos
Doença de Chagas/epidemiologia , Nitroimidazóis/farmacologia , Preparações Farmacêuticas , Trypanosoma cruzi/efeitos dos fármacos , Cromatografia em Camada Fina , Espectroscopia de Ressonância Magnética/métodos , Espectrofotometria InfravermelhoRESUMO
The nitroimidazole derivative Megazol is a highly active compound used against several strains of Trypanosoma cruzi, the causative agent of Chagas' disease (American trypanomiasis). With the aim of gaining an insight into the probable mode of action, the interaction of Megazol with different redox enzymes was studied in comparison to that of Nifurtimox and Metronidazole. The three nitroaromatic compounds are reduced by L-lactate cytochrome c-reductase, adrenodoxin reductase, and NADPH:cytochrome P-450 reductase (EC 1.6.2.4), the efficiencies of the enzymatic reductions being roughly related to the reduction potentials of these pseudo-substrates. As the enzyme responsible for the reduction of Megazol within the parasite has not yet been identified, the nitroimidazole was assayed with T. cruzi lipoamide dehydrogenase and trypanothione reductase. Megazol did not inhibit the physiological reactions but proved to be a weak substrate of both flavoenzymes. The single electron reduction of the compound by NADPH:cytochrome P-450 reductase, by rat liver as well as by trypanosome microsomes was confirmed by ESR experiments. As shown here, Megazol interferes with the oxygen metabolism of the parasite, but its extra activity when compared to Nifurtimox may be related to other features not yet identified.
Assuntos
Ferredoxina-NADP Redutase/metabolismo , Metronidazol/farmacocinética , NADH Desidrogenase/metabolismo , NADPH-Ferri-Hemoproteína Redutase/metabolismo , Nifurtimox/farmacocinética , Nitroimidazóis/farmacocinética , Tiadiazóis/farmacocinética , Animais , Biotransformação , Doença de Chagas/tratamento farmacológico , Doença de Chagas/parasitologia , Espectroscopia de Ressonância de Spin Eletrônica , L-Lactato Desidrogenase/metabolismo , L-Lactato Desidrogenase (Citocromo) , Estrutura Molecular , Oxirredução , Ratos , Trypanosoma cruzi/efeitos dos fármacosRESUMO
We report the case of a healthy young man presenting with atypical neutrophil alkaline phosphatase (NAP) and reduced neutrophil chemotactic activity, but with no susceptibility to infection. NAP activity was low, kinetic parameters were modified and immunoreactive properties and subcellular distribution were abnormal. Neutrophil morphology was normal. A similar pattern was observed in the patient's healthy brother. The profile of the observed anomalies offers some similarity to that previously described in patients with chronic myelogenous leukaemia. However, in the present case, the NAP deficiency with impaired neutrophil function was present in two brothers with no haematological symptoms and is probably related to a non-acquired neutrophil abnormality. This observation of a primary NAP variant reinforces the hypothesis of a direct link between NAP activity and functional properties of neutrophils.
Assuntos
Fosfatase Alcalina/deficiência , Neutrófilos/enzimologia , Neutrófilos/fisiologia , Adulto , Fosfatase Alcalina/antagonistas & inibidores , Fosfatase Alcalina/química , Núcleo Celular/enzimologia , Quelantes , Quimiotaxia de Leucócito , Citoplasma/enzimologia , Dimerização , Ácido Edético/farmacologia , Inibidores Enzimáticos/farmacologia , Humanos , Masculino , Microscopia Eletrônica , Neuraminidase/farmacologia , Neutrófilos/ultraestrutura , Ureia/farmacologiaRESUMO
Aldolase presents the same binding affinity for dihydroxyacetone phosphate and its phosphonomethyl analog, but the partition coefficient between the intermediates from the Michaelis complex to the eneamine is different. The effects of the structural modification of the triose phosphate substrate on the interaction with rabbit muscle aldolase are discussed in connection with the mechanistic pathway and the three-dimensional structure of the enzyme.
Assuntos
Fosfato de Di-Hidroxiacetona/análogos & derivados , Fosfato de Di-Hidroxiacetona/metabolismo , Frutose-Bifosfato Aldolase/metabolismo , Gliceraldeído 3-Fosfato/análogos & derivados , Compostos Organofosforados/metabolismo , Animais , Gliceraldeído 3-Fosfato/metabolismo , Iminas , Modelos Químicos , Músculos/enzimologia , CoelhosAssuntos
Hexoquinase/química , Hexoquinase/metabolismo , Trifosfato de Adenosina/metabolismo , Inibidores Enzimáticos/farmacologia , Glucosamina/metabolismo , Glucose/metabolismo , Hexoquinase/antagonistas & inibidores , Cinética , Conformação Proteica , Saccharomyces cerevisiae/enzimologia , Espectroscopia de Infravermelho com Transformada de Fourier , Especificidade por Substrato , Água/químicaRESUMO
This review underlines the importance of different enzymes (beta-glucocerebrosidase, phospholipase A2, proteases and cholesterol sulfatase) in the formation and maintenance of the epidermal barrier function. Certain diseases may be characterized by the lack or excess of one or more of these different enzyme activities, altering the homeostatic equilibrium of the epidermis. In addition to this, particular enzymes may show potential in the development of novel dermocosmetic strategies.