A comprehensive review on tyrosinase inhibitors.

Tyrosinase is a multi-copper enzyme which is widely distributed in different organisms and plays an important role in the melanogenesis and enzymatic browning. Therefore, its inhibitors can be attractive in cosmetics and medicinal industries as depigmentation agents and also in food and agriculture industries as antibrowning compounds. For this purpose, many natural, semi-synthetic and synthetic inhibitors have been developed by different screening methods to date. This review has focused on the tyrosinase inhibitors discovered from all sources and biochemically characterised in the last four decades.

Epidemiology of skin ulceration disease in wild sea cucumber Holothuria arguinensis, a new aquaculture target species.

Interest in wildlife epidemiology has increased in recent years. The control of diseases is critical for the survival of natural populations of economically valuable species. The present study is the first investigation of the etiology and epidemiology of skin ulceration disease in the sea cucumber Holothuria arguinensis, a new target species for fisheries and aquaculture in Europe. Bacterial cultures and molecular techniques were used to characterize this disease in animals collected during a survey across Ría Formosa Natural Park coastal lagoon in southern Portugal. Vibrio gigantis and V. crassostreae, which were both originally identified as disease agents in cultured oysters, were the most commonly isolated species of bacteria. Given that both sampling areas from which symptomatic H. arguinensis were collected were close to open oyster aquaculture facilities, this raises the possibility of an opportunistic infection, perhaps secondary to a decreased immune response caused by biotic or abiotic factors. An increase in prevalence of skin ulceration disease during the warmer season suggests that solar radiation and desiccation due to air exposure during low tide could be a cause of abiotic stress in the lagoon. Distributions of abundance and sizes of H. arguinensis in affected areas showed highest morbidity rates in adults. High fishery pressures throughout the study period could also cause elevations in prevalence and incidence rate of this disease. Skin ulcerative disease is endemic in this coastal lagoon. Disease monitoring is thus essential for the development of a conservation program to ensure the sustainability of fisheries and protection of natural resources.

Distal lower extremity coverage by distally based sural flaps: Methods to increase their vascular reliability.

INTRODUCTION: Although using distally based sural flaps is old and common, the described harvesting methods vary and often depend on unclear vascular anatomical data. We wanted, through a review of the existing harvesting techniques and our clinical experience, to synthesize these aspects in order to provide an optimal, safe and customized use of distally based sural flaps. PATIENTS AND METHODS: Fifty-eight sural flaps were performed in 53.4-year-old patients in average, presenting in 81% of the cases one or more vascular comorbidities. The mean cover surface was of 30cm2. The flaps were mainly fasciocutaneous. The tunneling of the pedicle was performed in 34.5% of the cases. A skin blade was preserved above the pedicle in 37.9% of flaps. The short saphenous vein was anastomosed in 27.6% of the cases at the recipient site and ligatured distally in 19% of the cases. The mean follow-up was 18.9months. RESULTS: In 31% of cases, the skin paddle presented an obvious venous congestion during flap inset successfully treated with an anastomosis or a distal ligature of the short saphenous vein. We noticed in six other flaps (10.3%) a postoperative venous congestion having led to a skin paddle partial necrosis, of which five (8.6%) were treated without compromising the quality of the reconstruction. One patient required a coverage using another flap. CONCLUSION: When the microsurgery is not required or possible, the distally based sural flaps represent a safe level of the reconstructive armamentarium. Managing the pedicle's dissection and the venous drainage needs to be discussed case-by-case and adapted to peroperatory observations. The anastomosis or ligation of the small saphenous vein, as the existence of a thin skin blade under the skin paddle appear to increase vascular reliability of these flaps.

[Geometrical growth models of the fetal forebrain, cerebellum, brainstem and change of the cranial base angles during fetal period]. / Modèles géométriques de croissance du cerveau, cervelet, tronc cérébral et modification des angles de la base du crâne au cours de la période fœtale.

INTRODUCTION: Brain growth plays likely an important role for the skull growth. In the fetus, there exists an heterochrony for the growth of supratentorial (forebrain) and infratentorial regions (brainstem and cerebellum). The aim of the study was thus to model geometrically the growth of these two regions and to compare it with the inflection of the base of skull. MATERIAL AND METHODS: Brain growth measurements were performed from midsagittal photographs of fetal brains obtained from an Anatomical Atlas over a period from 10 to 40 amenorrhea weeks (AW). After countouring and pointing anatomical and geometrical landmarks, we have developed a linear growth model based on principal component analysis (PCA). Besides, the variation of the sphenoidal and clivo-foraminal angles was studied from anatomical midsagittal slices of fetal heads sampled over a period from 16 to 39 AW. RESULTS: The PCA model brings to light the radial expansion of the forebrain growth (first component) associated with an inferior and posterior rotation of the occipital lobe. The growth of the infratentoriel region presents an inferior and posterior expansion associated with a second component corresponding to inferior and anterior expansions. From the 17 AW, appears an heterochrony between the supra- and infratentorial growths and an inversion of the ratio between the infra- and supratentorial dimensions after 30 AW. The sphenoidal and clivo-foraminal angles decrease slightly until 25 AW, and then increase quickly until the 39 AW. CONCLUSIONS: The growth of brain is accompanied by morphological change between the compartments supra- and infratentoriel but also on the level of the base of skull. The possible interactions will be discussed.

Assay of acetylcholinesterase activity by potentiometric monitoring of acetylcholine.

An acetylcholine-selective electrode based on a plasticized polymeric membrane has been developed. The electrode exhibited good selectivity for acetylcholine (ACh) over choline and some common ions, low drift, and a fast response to ACh. The response was linear over an ACh concentration range of 1×10(-6) to 1×10(-3) M with a slope of 59.1±0.1 and a detection limit of 1.5×10(-7)±1.2×10(-8) M. The electrode was used to monitor enzymatic ACh hydrolysis catalyzed by acetylcholinesterase (AChE) at different substrate and enzyme concentrations. A kinetic data analysis permitted the determination of the Michaelis-Menten constant of the enzymatic hydrolysis and AChE activity in the range of 2×10(-5) to 3.8×10(-1)U ml(-1).

Tyrosinase inactivation in its action on dopa.

Under aerobic or anaerobic conditions, tyrosinase undergoes a process of irreversible inactivation induced by its physiological substrate L-dopa. Under aerobic conditions, this inactivation occurs through a process of suicide inactivation involving the form oxy-tyrosinase. Under anaerobic conditions, both the met- and deoxy-tyrosinase forms undergo irreversible inactivation. Suicide inactivation in aerobic conditions is slower than the irreversible inactivation under anaerobic conditions. The enzyme has less affinity for the isomer D-dopa than for L-dopa but the velocity of inactivation is the same. We propose mechanisms to explain these processes.

Melanogenesis inhibition by tetrahydropterines.

There is controversy in the literature concerning the action of tetrahydropterines on the enzyme tyrosinase and on melanogenesis in general. In this study, we demonstrate that tetrahydropterines can inhibit melanogenesis in several ways: i) by non-enzymatic inhibition involving purely chemical reactions reducing o-dopaquinone to L-dopa, ii) by acting as substrates which compete with L-tyr and L-dopa, since they are substrates of tyrosinase; and iii) by irreversibly inhibiting the enzymatic forms met-tyrosinase and deoxy-tyrosinase in anaerobic conditions. Three tetrahydropterines have been kinetically characterised as tyrosinase substrates: 6-R-L-erythro-5,6,7,8-tetrahydrobiopterin, 6-methyl-5,6,7,8-tetrahydropterine and 6,7-(R,S)-dimethyl-5,6,7,8-tetrahydropterine. A kinetic reaction mechanism is proposed to explain the oxidation of these compounds by tyrosinase.

Implant retention and high rate of treatment failure in hematogenous acute knee and hip prosthetic joint infections.

OBJECTIVES: Only few studies evaluated hematogenous prosthetic joint infections. We aimed to describe the characteristics of these infections and factors associated with management failure. METHODS: We selected hematogenously-acquired infections, defined by the occurrence of infectious symptoms more than a year after implantation among records of patients treated for hip and knee prosthetic joint infections at Montpellier University Hospital between January 2004 and May 2015. Failure was defined by death due to prosthesis-related infection, need for prosthesis removal in case of conservative treatment, or recurrence of infectious signs on a new prosthesis. RESULTS: Forty-seven patients with hematogenous prosthetic joint infection were included (33 knee infections and 14 hip infections). Infectious agents were streptococci (43%), Staphylococcus aureus (43%), Gram-negative bacilli (13%), and Listeria monocytogenes (2%). Thirty-one patients were initially treated with debridement and implant retention and 15 with prosthesis removal (three with one-stage surgery, 10 with two-stage surgery). The median duration of antibiotic therapy was 66.5 days. The overall failure rate was 52% (24/48), 71% (22/31) with implant retention strategy, 13% (2/15) with prosthesis removal, and 63% (12/19) in case of Staphylococcus aureus infection. Conservative treatment was appropriate (arthrotomy on a well-implanted prosthesis without sinus tract and symptom onset <21 days) in 13/31 patients (42%) with a failure rate still high at 69% (9/13). The only factor associated with failure was conservative surgical treatment. CONCLUSION: The high risk of failure of conservative treatment for hematogenous prosthetic joint infections should lead to considering prosthesis replacement as the optimal strategy, particularly with Staphylococcus aureus.

Cortical and trabecular bone distribution in the femoral neck in osteoporosis and osteoarthritis.

The increased hip fragility in osteoporosis has been attributed mainly to a thinning of the cortex. In contrast, hip arthritis (OA) is not associated with increased risk of hip fracture. The purpose of this study was to assess cortical and trabecular bone structures and their possible regional variability in the femoral neck taken from patients who sustained an osteoporotic hip fracture (OP) compared with patients with OA. We compared the distribution of bone in the ultradistal femoral neck in 21 postmenopausal women with OA (mean age: 66+/-7.8 years) and 20 postmenopausal women with an osteoporotic hip fracture (OP) (mean age: 79.5+/-1.9 years). Controlateral hip osteoporosis or osteopenia was confirmed in OP by DEXA (T-score: -2.5+/-0.8 in OP; -0.9+/-1.3 in OA). Histomorphometric parameters of bone structure, architecture and connectivity were measured on sections from the ultradistal part of the femoral neck, divided in 4 quadrants. When compared to OA, cortical thickness was significantly decreased in OP (p<0.0005) but was the highest in the inferior part in both groups. Cortical porosity was higher in OA (13.48+/-1.02 and 8.4+/-1.07% in OA and OP respectively). Compared to OA, the trabecular bone volume was decreased by 50% in OP (p<0.0001) with a diminution of the trabecular number (p<0.01) and thickness (p<0.0001). In parallel, OP group was characterized by a poor connectivity evaluated by the decreased number of nodes (p<0.0001), higher trabecular bone pattern factor (p<0.0001) and greater marrow star volume (p<0.0001). The connectivity was the lowest in the inferior quadrant in OP but not in OA. Our data suggest that in addition to the cortical thinning, the loss of the trabecular bone mass and connectivity plays a role in the skeletal fragility associated with hip fracture. Furthermore, the spatial distribution of the trabeculae differs between OP and OA whereas cortical thinning is homogenous.

[Degenerative cartilage changes in metatarsosesamoidal joint and Scarf procedure results for hallux valgus: a prospective study of 100 cases]. / Les lésions cartilagineuses métatarsosésamoïdiennes dans les résultats de l'ostéotomie Scarf: A propos d'une série prospective de 100 cas.

PURPOSE OF THE STUDY: Sesamoid bones of the hallux play a major role in the biomechanics of the metatarsophalangeal complex. Due to the deformations resulting from hallux valgus, the sesamoid system is exposed to abnormal stress forces. Mapping the degenerative cartilage shows the significant prevalence of these lesions and their relation with the anatomic deformation. The purpose of this work was to determine the impact of these metatarsosesamoidal joint changes on the results of Scarf procedure for hallux valgus. MATERIAL AND METHODS: This series included 89 patients (100 feet) who underwent Scarf osteotomy with complementary phalangeal osteotomy. We distinguished two groups in this cohort: 78 cases of surgery not involving the lateral metatarsals (group A), and 22 cases with associated lateral metatarsal osteotomy (group B). Mean follow-up was 2.3 years; minimal follow-up 16 months. The study protocol was prospective, with preoperative and last follow-up radiological and clinical assessment by an independent operator. Joint lesions noted intraoperatively by one senior operator were noted. The clinical work-up included the AOFAS score. A 15 degrees anteroposterior weight-bearing view was used to determine the degree of sesamoid dislocation and measure the following angles: first metatarsophalangeal angle (M1P1), first intermetatarsal space (M1M2), proximal articular set angle (PASA). Eleven zones were described to map the joint surfaces. The statistical analysis was used to search for links between joint lesions and the radiographic and clinical findings. RESULTS: The joint cartilage analysis revealed lesions involving the sesamoid bones in 72 cases, with a preferential involvement of the medial sesamoid bone (67%). The plantar joint surface of the first metatarsal presented lesions in the medial gutter in 72 cases, and in the lateral gutter in 68. Complete absence of the intersesamoid crest was noted in 38%. The metatarsophalangeal compartment presented degenerative lesions in 15 cases. The preoperative assessment noted a positive significant correlation between the AOFAS overall score and the absence of lesions involving the lateral sesamoid bone (p=0.015), between the AOFAS pain score and the absence of lesions involving the lateral sesamoid bone (p=0.022), between the AOFAS pain score and the complete absence of the intersesamoid crest (p=0.001), between the AOFAS deviation score and the absence of lesion involving the lateral gutter (p=0.001), between the M1P1 angle and the absence of an intersesamoid crest (p=0.001). At last follow-up, there was a positive significant correlation between the absence of lesions involving the medial sesamoid bone and a better overall AOFAS score (p=0.014), between absence of a lateral sesamoid lesion and better postoperative sentering of the sesamoids (p=0.014), between the absence of lesion in the medial gutter and a higher postoperative M1P1 angle (p=0.002), between the absence of lesions involving the lateral gutter and more favorable overall AOFAS score (p=0.005) for function (p=0.022), and deviation (p=0.018), between the absence of intersesamoid crest lesions and better radiographic sesamoid recentering (p=0.020). Distinct analysis of groups A and B did not demonstrate a significant difference compared with the overall cohort. Comparison of the two groups only demonstrated three significant differences involving radioclinical parameters. DISCUSSION: Hallux valgus is associated with very frequent metatarsosesamoid lesions. The distribution of these lesions is a function of the anatomic and biomechanical features of the metatarsosesamoid joint surfaces. Lesions to the lateral compartment would be a poor prognostic factor for Scarf procedure.

[Degenerative changes of the metatarso-sesamoido-phalangeal complex]. / Lésions dégénératives du complexe métatarso-sésamoïdo-phalangien.

OBJECTS: The aim of this work was to determine the frequency and the location of the degenerative lesions of the hallucal metatarsophalangeal joint in an elderly population. Our results help us to precise the anatomic characteristics of that articular complex. METHODS: Our material comprised 21 feet from embalmed cadaver specimens. We studied the morphometrical parameters for the anatomic description of the first metatarsophalangeal joint of the forefoot. After complete dissection, a specific articular zone-mapping was made with a quantitative evaluation of the chondral lesions. MAIN RESULTS: The measurements of the morphometrical parameters were in accordance with the literature data. The sesamoidal chondral lesions were more frequent for the medial sesamoid and at the proximal zone of the articular surface. The plantar metatarsal lesions were very frequent with diffuse or distal groove damage, and crista damage linked to the sesamoidal strap dislocation. The lesions involving the metatarsophalangeal compartment were less frequent and rather at the dorsal zone. CONCLUSIONS: The degenerative lesions of the metatarso-sesamoido-phalangeal complex are nearly systematic in n elderly population. The morphological aspect of these lesions is very characteristic of the articular function and allows us to precise the biomechanic constraints.

Quality of life after total knee arthroplasty.

Total knee arthroplasty (TKA) results in a high degree of patient satisfaction, as it provides patients with considerable medium- and long-term benefits in terms of quality of life, pain relief and function. Nevertheless, the literature reports that up to 30% of patients are dissatisfied. This dissatisfaction is directly related to the patients' quality of life, which they deem insufficient. Their quality of life depends on many physical, behavioural, social and psychological factors that are not taken into account by functional outcome scores. After describing the principles of quality of life evaluation after TKA, we will assess the effects of patient-related factors, the surgical technique and postoperative program through an exhaustive review of the literature. Patient expectations after TKA will then be outlined, particularly return to work and return to sports.

An approximate analytical solution to the lag period of monophenolase activity of tyrosinase.

Tyrosinase shows a lag period in its action on monophenols (l-tyrosine). We propose an approximate analytical solution for the lag period, which fulfils the dependences with regard to initial enzyme concentration, and initial monophenol concentration. Furthermore, from a study of the dependences of the lag period on these variables, we can determine experimentally the o-diphenol concentration in the steady state. The Michaelis constant of the o-diphenol in the presence of the monophenol can be determined from the relationship between the o-diphenol concentration in the steady state and the initial monophenol concentration, taking into consideration the experimentally calculated Michaelis constant for the monophenol substrate. Although this Michaelis constant is much lower than the Michaelis constant for diphenol in the absence of monophenol, the binding site is the same. A kinetic analysis of the action mechanism of tyrosinase explains this difference in the values of the Michaelis constants.

A review on spectrophotometric methods for measuring the monophenolase and diphenolase activities of tyrosinase.

Tyrosinase is a copper enzyme with broad substrate specifity toward a lot of phenols with different biotechnological applications. The availability of quick and reliable measurement methods of the enzymatic activity of tyrosinase is of outstanding interest. A series of spectrophotometric methods for determining the monophenolase and diphenolase activities of tyrosinase are discussed. The product of both reactions is the o-quinone of the corresponding monophenol/diphenol. According to the stability and properties of the o-quinone, the substrate is classified as four substrate types. For each of these substrate types, we indicate the best method for measuring diphenolase activity (among eight methods) and, when applicable, for measuring monophenolase activity (among four methods). The analytical and numerical solutions to the system of differential equations corresponding to the reaction mechanism of each case confirm the underlying validity of the different spectrophotometric methods proposed for the kinetic characterization of tyrosinase in its action on different substrates.

Kinetic characterization of the oxidation of chlorogenic acid by polyphenol oxidase and peroxidase. Characteristics of the o-quinone.

Chlorogenic acid is the major diphenol of many fruits, where it is oxidized enzymatically by polyphenol oxidase (PPO) or peroxidase (POD) to its o-quinone. In spectrophotometric studies of chlorogenic acid oxidation with a periodate ratio of [CGA]0/[IO4-]0 < 1 and [CGA]0/[IO4-]0 > 1, the o-quinone was characterized as follows: lambda(max) at 400 nm and epsilon = 2000 and 2200 M-1 cm-1 at pH 4.5 and 7.0, respectively. In studies of o-quinone generated by the oxidation of chlorogenic acid using a periodate at ratio of [CGA]0/[IO4-]0 > 1, a reaction with the remaining substrate was detected, showing rate constants of k = 2.73 +/- 0.17 M-1 s-1 and k' = 0.05 +/- 0.01 M-1 s-1 at the above pH values. A chronometric spectrophotometric method is proposed to kinetically characterize the action of the PPO or POD on the basis of measuring the time it takes for a given amount of ascorbic acid to be consumed in the reaction with the o-quinone. The kinetic constants of mushroom PPO and horseradish POD are determined.

Thresholds and management strategies for Aulacorthum solani (Hemiptera: Aphididae) in greenhouse pepper.

Economic injury level (EIL) and economic threshold (ET) were established for Aulacorthum solani (Kaltenbach) (Hemiptera: Aphididae) in greenhouse pepper, Capsicum annuum L. The high toxicity of the salivary secretion of A. solani produces deformation and decoloration of leaves, complete plant defoliation, and unmarketable deformed fruits at high densities. Low, high and null infestation rate treatments provided a broad range of population densities to determine the relationship between yield and the cumulative A. solani-days (CAD). In all infested compartments, A. solani reached a very high population density that eventually produced the complete defoliation of the plants and losses in total and marketable yield. At low A. solani density, pepper plants showed a tolerance response. Generalized Additive Models (GAM) and Gompertz equation were used to determine the relationship between yield and CAD. Both models explained a high proportion of the variance and described well the relationship between the two variables. However, GAM predicted the tolerance phase of the yield-CAD relationship more satisfactorily. The theoretical damage curve predicted by GAM describes a tolerance, compensation and a linearity part. EIL was estimated at 57 CAD. ET was established at 20 CAD to prevent aphid density from reaching EIL within the gap between sampling periods.

Ethical problems related to information and pharmaceutical care in Spain.

This paper represents a reflection on the limits and objectives of the information pharmacists should offer in pharmacies. The obligation of a pharmacist to follow the patient's therapeutic progress makes it necessary to integrate this figure into an ethical-legal framework and to define the objective of the health-related information offered, taking into account the patient's welfare and constitutional rights.

Global fit concept in revision hip arthroplasty for cementless press-fit femoral stems.

A revision stem may be required after a femoral extended trochanteric osteotomy (ETO) is made during revision hip arthroplasty. The two main complications of straight cementless femoral stems are subsidence due to inadequate osteointegration and stress-shielding. We will describe an original revision method with ETO that uses a straight cementless stem. The goal of this method was to achieve the most extensive press-fit possible during stem implantation to improve the transmission of stresses to the bone and to prevent reduction in bone density. The intramedullary preparation was done after closure and fixation of the ETO, which allows impaction of the revision stem with metaphyseal and diaphyseal press-fit. We report encouraging results with preservation of periprosthetic bone stock and good osteointegration of these revision stems at the final follow-up. Pronounced sagittal curvature or large bone defects are contraindications for this technique.

Transient-phase kinetics of enzyme inactivation induced by suicide substrates.

This paper deals with the kinetic study of reaction mechanisms with enzyme inactivation induced by a suicide substrate in the presence or absence of an auxiliary substrate and in conditions of excess of substrates in relation to the enzyme concentration and vice versa. A transient-phase approach has been developed that enables explicit equations with one or two significant exponentials to be obtained, thereby showing the dependence of product concentration on time. The validity of these equations has been checked, and a comparison made with those previously obtained by other authors. We propose an experimental design to determine the corresponding parameters and kinetic constants. The simplicity of our method allows a systematic application to more complex mechanisms.

Kinetic study on the suicide inactivation of tyrosinase induced by catechol.

Tyrosinase has a suicide inactivation reaction when it acts on omicron-diphenols. In the present paper, this reaction has been studied using a transient phase approach. Explicit equations of product vs. time have been developed for the multisubstrate mechanism of tyrosinase, and the kinetic parameters which characterize the enzyme acting on the suicide substrate catechol have been determined. The effect of pH has also been considered.