The Isolation of Specialty Compounds from Amphidinium carterae Biomass by Two-Step Solid-Phase and Liquid-Liquid Extraction.

The two main methods for partitioning crude methanolic extract from Amphidinium carterae biomass were compared. The objective was to obtain three enriched fractions containing amphidinols (APDs), carotenoids, and fatty acids. Since the most valuable bioproducts are APDs, their recovery was the principal goal. The first method consisted of a solid-phase extraction (SPE) in reverse phase that, for the first time, was optimized to fractionate organic methanolic extracts from Amphidinium carterae biomass using reverse-phase C18 as the adsorbent. The second method consisted of a two-step liquid-liquid extraction coupled with SPE and, alternatively, with solvent partitioning. The SPE method allowed the recovery of the biologically-active fraction (containing the APDs) by eluting with methanol (MeOH): water (H2O) (80:20 v/v). Alternatively, an APD purification strategy using solvent partitioning proved to be a better approach for providing APDs in a clear-cut way. When using n-butanol, APDs were obtained at a 70% concentration (w/w), whereas for the SPE method, the most concentrated fraction was only 18% (w/w). For the other fractions (carotenoids and fatty acids), a two-step liquid-liquid extraction (LLE) method coupled with the solvent partitioning method presented the best results.

Effect of Nitrogen, Phosphorous, and Light Colimitation on Amphidinol Production and Growth in the Marine Dinoflagellate Microalga Amphidinium carterae.

The marine dinoflagellate microalga Amphidinium carterae is a source of amphidinols, a fascinating group of polyketide metabolites potentially useful in drug design. However, Amphidinium carterae grows slowly and produces these toxins in tiny amounts, representing a hurdle for large-scale production. Understanding dinoflagellate growth kinetics under different photobioreactor conditions is imperative for promoting the successful implementation of a full-scale integrated bioproduct production system. This study evaluates the feasibility of growing Amphidinium carterae under different ranges of nitrogen concentration (NO3- = 882-2646 µM), phosphorus concentration (PO33- = 181-529 µM), and light intensity (Y0 = 286-573 µE m-2 s-1) to produce amphidinols. A mathematical colimitation kinetic model based on the "cell quota" concept is developed to predict both algal growth and nutrient drawdown, assuming that all three variables (nitrogen, phosphorous and light) can simultaneously colimit microalgal growth. The model was applied to the semicontinuous culture of the marine microalgae Amphidinium carterae in an indoor LED-lit raceway photobioreactor. The results show that both growth and amphidinol production strongly depend on nutrient concentrations and light intensity. Nonetheless, it was possible to increase Amphidinium carterae growth while simultaneously promoting the overproduction of amphidinols. The proposed model adequately describes Amphidinium carterae growth, nitrate and phosphate concentrations, and intracellular nitrogen and phosphorus storage, and has therefore the potential to be extended to other systems used in dinoflagellate cultivation and the production of bioproducts obtained therein.

Mesotherapy With Dutasteride for Androgenetic Alopecia: A Retrospective Study in Real Clinical Practice.

BACKGROUND: 5-alpha inhibitors are an effective treatment for androgenetic alopecia. Mesotherapy with dutasteride has been proposed as an effective method to improve hair loss and reducing systemic absorption. OBJECTIVE: The main objective was to describe the safety profile of mesotherapy with dutasteride in real clinical practice in a large cohort of patients with androgenetic alopecia. A secondary aim was to describe the effectiveness of this treatment. METHODS AND MATERIALS: A multicentric retrospective study was designed. Patients treated with at least 6 months of follow-up were included in the study. Side effects and response to the treatment were analyzed. RESULTS: A total of 541 patients were included. The commonest approach during the first year was to perform the treatment every 3 months. Response to the mesotherapy in monotherapy could be assessed in 86 patients (15.9%) after one year. Most of them presented clinical improvement, being a marked improvement in 33 patients (38.4%). Pain was the most frequent side effect of the treatment (246 patients, 45.5%). No serious or sexual adverse events were detected. CONCLUSION: Mesotherapy with dutasteride was effective in male and female hair loss in real clinical practice. Side effects related to the treatment were mild and self-limited. This therapy may be an effective option for select patients wishing to avoid oral treatment. J Drugs Dermatol. 2022;21(7):742-747. doi:10.36849/JDD.6610.

The Benefit of Perineural Injection Treatment with Dextrose for Treatment of Chondromalacia Patella in Participants Receiving Home Physical Therapy: A Pilot Randomized Clinical Trial.

Introduction: Chondromalacia patella is the degeneration of articular cartilage on the posterior facet of the patella and may indicate the onset of osteoarthritis. Conservative management is the main treatment option, and surgical intervention is considered the last option in a small percentage of patients. Perineural Injection Treatment (PIT) is a recently developed treatment option that is directed adjacent to the peripheral nerves that are the source of pathology causing neurogenic inflammation and pain. Objective: The objective of this study was to evaluate the efficacy of PIT combined with a home physical therapy program in patients with a diagnosis of chondromalacia patella compared with a control group receiving physical therapy only. Methods: Two patient groups were involved in this randomized clinical trial. The first received PIT combined with physical therapy (PIT + PT group) and the second was managed with physical therapy alone (PT group). Both groups were indicated to follow a 6-week home therapy plan afterward. The Western Ontario and McMaster Osteoarthritis Index was used to assess the patients at baseline and 6 months after therapy interventions. Results: Fifty patients (38 women and 12 men, median age 54.7 ± 14.8 years) were included; sex distribution and age did not differ between groups. Both groups had chondromalacia grade II or III, but the degree of gonarthrosis did not differ significantly between groups. The PIT + PT group outperformed PT group for pain (7.3 ± 3.5 vs. 3.2 ± 2.9 points; p < 0.010), stiffness (3 ± 1.69 vs. 1.6 ± 1.5 points; p < 0.010), and functional capacity (23.2 ± 10.7 vs. 11.1 ± 8.9 points; p < 0.010). Conclusions: Compared with physical therapy alone, PIT plus physical therapy reduced pain and stiffness and restored functional capacity. ClinicalTrials.gov Register Number #NCT03515720.

[Effectiveness of antimicrobial formulations for acne based on orange (Citrus sinensis) and sweet basil (Ocimum basilicum L) essential oils]. / Diseño y evaluación in vivo de fórmulas para acné basadas en aceites esenciales de naranja (Citrus sinensis), albahaca (Ocimum basilicum L) y ácido acético.

INTRODUCTION: Currently, the antimicrobial resistance has developed in bacterial strains involved in the development of acne. Therefore, alternatives to antibiotic treatment have become necessary. OBJECTIVES: Gel formulations were designed based on essential oils and acetic acid, and their effectiveness was evaluated in patients affected by acne. MATERIALS AND METHODS: Masked simple experimental study of three gel formulations on 28 volunteer patients, separated in four groups of seven patients. Treatments were applied daily for eight weeks and consisted of (1) antibacterial (essential oils), (2) keratolytic medication (3) essential oils mixed with acetic acetic, and (4) kerolytic medication with acetic acid. Weekly checks were conducted to evaluate patient improvement. RESULTS: All groups reported an improvement of the acne condition, which ranged between 43% and 75% clearance of lesions. Evidence of treatment disappeared within minutes, showing little discomfort or side effects after application. CONCLUSIONS: The essential oil formulations were chemically and physically stable during application of treatments. This was demonstrated by gas chromatography, where no evidence no change neither the composition profiles of essential oils nor in acetic acid. The results were ranked good to excellent, particularly for the acetic acid mixture, which achieved improvements of 75%. This appeared to be a result of their joint antiseptic and keratolytic activity. Side effects (burning and redness) disappeared within a few minutes of completing the application, therefore, did not interfere with adherence to treatment.

Diseño y evaluación in vivo de fórmulas para acné basadas en aceites esenciales de naranja (Citrus sinensis), albahaca (Ocimum basilicum L) y ácido acético / Effectiveness of antimicrobial formulations for acne based on orange (Citrus sinensis) and sweet basil (Ocimum basilicum L) essential oils

Introducción. Actualmente, la resistencia a los antimicrobianos de las cepas bacterianas involucradas en el desarrollo del acné es una realidad y se hace necesario buscar alternativas terapéuticas para su tratamiento. Objetivos. Diseñar fórmulas en gel a base de aceites esenciales y ácido acético, y evaluar su efectividad en pacientes voluntarios afectados por acné. Materiales y métodos. Se trata de un estudio experimental simple enmascarado de tres fórmulas en gel sobre cuatro grupos de siete pacientes. Los tratamientos antibacterianos (aceites esenciales), queratolíticos y mixtos (ácido acético), se aplicaron diariamente por espacio de ocho semanas. Se hicieron controles semanales para evaluar la evolución de los pacientes. Resultados. Todos los grupos reportaron mejoría (desaparición de las lesiones) de la condición del acné, la cual osciló entre 43 y 75 %, con leves efectos secundarios transitorios relacionados con la aplicación de los tratamientos utilizados. Conclusiones. Las fórmulas estudiadas mostraron ser estables química y físicamente durante la aplicación de los tratamientos, lo cual se demostró mediante análisis de cromatografía de gases, en la cual no se evidenció ningún cambio en los perfiles de composición de los aceites esenciales ni en el del ácido acético. Los resultados se catalogaron entre buenos y excelentes, en particular, el del ácido acético, que logró mejorías superiores al 75 %, dada su actividad mixta antiséptica y queratolítica. Los efectos secundarios (ardor y enrojecimiento) desaparecieron a los pocos minutos de realizada la aplicación y no impidieron el cumplimiento de los tratamientos.

Introduction. Currently, the antimicrobial resistance has developed in bacterial strains involved in the development of acne. Therefore, alternatives to antibiotic treatment have become necessary. Objectives. Gel formulations were designed based on essential oils and acetic acid, and their effectiveness was evaluated in patients affected by acne. Materials and methods. Masked simple experimental study of three gel formulations on 28 volunteer patients, separated in four groups of seven patients. Treatments were applied daily for eight weeks and consisted of (1) antibacterial (essential oils), (2) keratolytic medication (3) essential oils mixed with acetic acetic, and (4) kerolytic medication with acetic acid. Weekly checks were conducted to evaluate patient improvement. Results. All groups reported an improvement of the acne condition, which ranged between 43% and 75% clearance of lesions. Evidence of treatment disappeared within minutes, showing little discomfort or side effects after application. Conclusions. The essential oil formulations were chemically and physically stable during application of treatments. This was demonstrated by gas chromatography, where no evidence no change neither the composition profiles of essential oils nor in acetic acid. The results were ranked good to excellent, particularly for the acetic acid mixture, which achieved improvements of 75%. This appeared to be a result of their joint antiseptic and keratolytic activity. Side effects (burning and redness) disappeared within a few minutes of completing the application, therefore, did not interfere with adherence to treatment.

Immunoregulatory potential of marine algal toxins yessotoxin and okadaic acid in mouse T lymphocyte cell line EL-4.

We have studied the effects of the marine algal toxins yessotoxin (YTX) and okadaic acid (OA) on the T cell receptor complex (TCR) expression, an important mechanism by which T cell responsiveness is controlled. Immune system cells are relevant targets to study the immunoregulatory potential of marine toxins since the immune system has been reported as one of the targets of marine algal toxins. This study reports results from exposing the mouse T lymphocyte cell line EL-4 to increasing concentrations of YTX and OA for 72h. We found that both YTX and OA affected TCR recycling kinetics and induced a specific and reversible TCR down-regulation in T lymphocyte EL-4 cells that was time and concentration dependent. Experiments using the potent protein kinase C (PKC) inhibitor stausporine indicated that YTX-induced TCR down-regulation was partially mediated by PKC activation. In contrast, OA-induced TCR down-regulation was mediated by the serine/threonine protein phophatase 2A (PP2A) inhibition. In summary, the results suggest that OA and YTX concentrations in a similar range than those detected in mice bloodstream after oral administration have the potential to adjust the T cell responsiveness during the initiation of T cell activation by affecting the TCR expression levels via PKC and PP2A activities.

Two cases of cutaneous chronic graft versus host disease in treatment with psoralen plus ultraviolet-A-bath photochemotherapy.

BACKGROUND: Up to 50% of patients undergoing allogenic stem cell transplantation or bone marrow transplantation (BMT) can develop acute or chronic graft versus host disease (GVHD) as a severe complication. Immunosuppressive therapies may prove not only ineffective but may cause serious adverse effects. GVHD remains a major clinical problem and is often associated with high mortality rates. METHODS: This article presents the cases of a 48-year-old woman and a 23-year-old man, both presenting with severe cutaneous sclerodermic chronic GVHD following allogenic stem cell transplantation. Despite several years of treatment with oral corticosteroids, mycophenolate mofetil, sirolimus and acitretine, the skin lesions had not improved. Both patients were then treated with psoralen plus ultraviolet (PUVA)-bath photochemotherapy three times weekly, following a standardized treatment protocol. RESULTS: After a total accumulated dose of about 90 J/cm2, skin lesions in both patients had improved, showing complete remission in some body areas. Systemic corticosteroid treatment could be gradually reduced in the case of the female patient and skin conditions remained stable during maintenance treatment of PUVA-bath two times weekly and during a mean follow-up period of eight months. CONCLUSION: Oral PUVA therapy has been established as a successful treatment for acute and chronic GVHD, but unfortunately may result in systemic side effects. Psoralen plus ultraviolet-A-bath photochemotherapy provides clinicians with a therapeutic alternative that offers high clinical efficacy and safety. Therefore, PUVA-bath could be included as an alternative in the treatment protocol for chronic cutaneous GVHD.

[Skin infection with Fusarium in an immunocompetent patient]. / Infección cutánea por fusarium en paciente inmunocompetente.

Fusarium spp. are fungi found throughout the world and can cause a great variety of skin infections, mainly in immunodepressed individuals. We present a case of skin infection with Fusarium sp. which manifested as painful superficial ulcers on the legs of an immunocompetent female patient, who had applied <> as a <> for leg pain. The condition was cured with oral itraconazole and local treatments.

Infección cutánea por fusarium en paciente inmunocompetente / Skin infection with fusarium in an immunocompetent patient

Fusarium spp. son hongos distribuidos por todo el mundo que pueden producir una gran variedad de infecciones cutáneas, principalmente en individuos inmunodeprimidos. Se presenta un caso de infección cutánea por Fusarium sp. que se manifestó como úlceras superficiales dolorosas en las piernas de una paciente inmunocompetente que se había aplicado «barros medicinales» como remedio «natural» para el dolor de piernas. Se obtuvo la curación con itraconazol oral y curas locales

Fusarium spp. are fungi found throughout the world and can cause a great variety of skin infections, mainly in immunodepressed individuals. We present a case of skin infection with Fusarium sp. which manifested as painful superficial ulcers on the legs of an immunocompetent female patient, who had applied «medicinal mud» as a «natural remedy» for leg pain. The condition was cured with oral itraconazole and local treatments

Oral and topical L-phenylalanine, clobetasol propionate, and UVA/sunlight--a new study for the treatment of vitiligo.

BACKGROUND: Vitiligo is a hypopigmented skin condition that usually requires a combination of treatment options. AIM: To demonstrate the effectiveness of topical and oral L-phenylalanine in combination with light plus 0.025% clobetasol propionate at night. PATIENTS AND METHODS: We have performed an open trial on a group of 70 patients with evolutive vitiligo. Participants were treated with oral (100 mg/Kg/day) and topical (gel at 10%) L-phenylalanine, exposed to sunlight (spring-summer) or UVA lamps (autumn-winter), and given 0.025% clobetasol propionate at night. All patients were revisited every 6 months while in the study, with a maximum of 4 revisits. Biochemical studies were performed at the beginning of the treatment and at each revisit. RESULTS: Overall, 90.9% of participants showed improvement, with 68.5% of patients achieving an improvement of 75% or more. This 75% improvement rate was reached 87.9% of the time on the face, 60.4% on the trunk, and 54.6% on the limbs. However, there was a moderate response to the treatment in patients with focal and segmental vitiligo. There was a slight additional improvement in patients receiving UVA lamp light. No biochemical abnormalities were found in any patients. CONCLUSION: L-phenylalanine in combination with 0.025% clobetasol propionate and sunlight during sunny months or UVA lamps in winter, appears to improve evolutive vitiligo without side effects, and therefore is especially recommended on the face or for children.