The Oral Delivery of Water-Soluble Phenol TS-13 Ameliorates Granuloma Formation in an In Vivo Model of Tuberculous Granulomatous Inflammation.

The redox-sensitive signaling system Keap1/Nrf2/ARE is a premier protective mechanism against oxidative stress that plays a key role in the pathogenesis and development of various diseases, including tuberculous granulomatous inflammation. We have previously reported that novel water-soluble phenolic antioxidant TS-13 (sodium 3-(4'-methoxyphenyl)propyl thiosulfonate) induces Keap1/Nrf2/ARE and attenuates inflammation. The aim of this study is the examination of the effect of TS-13 on tuberculous granulomatous inflammation. BALB/c mice were administered TS-13 (100 mg kg-1 day-1) through their drinking water starting immediately after Bacillus Calmette-Guérin (BCG) intravenous injection. Histological changes, production of reactive oxygen species (ROS) (activity of free-radical oxidation processes), and mRNA expression of Nrf2-driven, NF-κB-, AP-1-, and autophagy-dependent signal pathway genes in the liver and peritoneal exudate were evaluated 30 days later. After the 30th day of infection, the activity of the Keap1/Nrf2/ARE system was decreased and its effector genes entailed increasing ROS production in the liver. Therapeutic intervention with TS-13 is aimed at activating the Keap1/Nrf2/ARE system that leads to an increase in Nrf2 and Nrf2-mediated gene expression and a decrease in NF-κB expression. Changes in these pathways resulted in a decline of ROS production and a decrease in the number and the size of granulomas. In total, the results indicate that the Keap1/Nrf2/ARE system can be an effective pharmacological target in host-adjunctive treatment of tuberculosis.

Erianin regulates programmed cell death ligand 1 expression and enhances cytotoxic T lymphocyte activity.

ETHNOPHARMACOLOGICAL RELEVANCE: Dendrobium chrysotoxum Lindl is a cultivation of Dendrobium which belongs to the family of Orchidaceae. D. chrysotoxum Lindl is a traditional Chinese medicine with a wide range of clinical applications including tonic, astringent, analgesic and anti-inflammatory properties as early as the 28th century B.C. Erianin is a representative index component for the quality control of the D. chrysotoxum Lindl, which is included in the Pharmacopoeia of the People's Republic of China (2020 version). AIM OF THE STUDY: To clarify the anti-tumour mechanisms of erianin in vitro and in vivo. MATERIALS AND METHODS: We detected the anti-tumour activity of erianin using in vitro HeLa cell models and in vivo cervical cancer xenograft models. We performed MTT, western blot, RT-PCR, homology modeling, flow cytometry, and immunoprecipitation assays to study the proteins, genes, and pathways related to erianin's anti-tumour activity. LysoTracker Red staining was performed to detect lysosome function. Transwell, wound healing, tube formation, colony formation and EdU labelling assays were performed to determine cell proliferation, migration and invasion abilities, respectively. Cytotoxic T lymphocytes ability was confirmed using HeLa/T-cell co-culture model. RESULTS: Experimental data demonstrated that erianin inhibited PD-L1 expression and induced the lysosomal degradation of PD-L1. Erianin suppressed HIF-1α synthesis through mTOR/p70S6K/4EBP1 pathway, and inhibited RAS/Raf/MEK/MAPK-ERK pathway. Immunoprecipitation experiments demonstrated that erianin reduced the interaction between RAS and HIF-1α. Experiments using a co-cultivation system of T cells and HeLa cells confirmed that erianin restored cytotoxic T lymphocytes ability to kill tumour cells. Erianin inhibited PD-L1-mediated angiogenesis, proliferation, invasion and migration. The anti-proliferative effects of erianin were supported using in vivo xenotransplantation experiments. CONCLUSIONS: Collectively, these results revealed previously unknown properties of erianin and provided a new basis for improving the efficacy of immunotherapy against cervical cancer and other malignant tumours through PD-L1.

Advanced chemical peels: Phenol-croton oil peel.

Once considered the standard for deep facial resurfacing, the classical Baker-Gordon phenol-croton oil peel has largely been replaced by formulas with lower concentrations of phenol and croton oil. The improved safety profile of deep peels has ushered in a new era in chemical peeling. Wrinkles can be improved and skin can be tightened with more subtle and natural results. No longer does a deep peel denote "alabaster white" facial depigmentation with complete effacement of wrinkles. Gregory Hetter's research showed that the strength and corresponding depth of penetration of the phenol-croton oil peel can be modified by varying the concentration of croton oil. This second article in this continuing medical education series focuses on the main historical, scientific, and procedural considerations in phenol-croton oil peels.

Endoscopic Pilonidal Sinus Treatment Combined With Crystalized Phenol Application May Prevent Recurrence.

BACKGROUND: No single treatment yet exists for pilonidal disease that has a short healing time, good cosmetic results, and a low rate of recurrence. Phenol crystal application and diathermy ablation through an endoscope have been used for the treatment of pilonidal disease, but this cohort is the first one to combine them. OBJECTIVE: The purpose of this study was to examine the safety, effectiveness, and short- and long-term outcomes of crystalized phenol treatment combined with endoscopic pilonidal sinus treatment for pilonidal disease. DESIGN: This was a prospective cohort study. SETTINGS: Procedures were performed in 2 hospitals by the same surgeon between February and July 2014. PATIENTS: Twenty-three patients underwent surgical treatment for pilonidal disease. INTERVENTIONS: Under local anesthesia and sedation, all of the patients underwent a video-assisted diathermy ablation of the sinus cavity and the application of phenol crystals. MAIN OUTCOME MEASURES: Adverse events were recorded as a measure of safety and tolerability. Failure to heal and recurrence rate were documented and evaluated. RESULTS: Patients were discharged on the same day as surgery. There was no or minimal postoperative pain (mean visual analog scale score, 1.40 ± 0.95). Mean operation time was 20.43 ± 6.19 minutes, and the median return-to-work duration was 2.00 days (mean, 3.03 ± 2.95 d). Patients were followed-up for 18 to 24 months (mean, 22.00 ± 1.88 mo). No serious complications or rehospitalization were observed. No primary failure to heal or recurrence was observed. LIMITATIONS: This study did not include a control group with which to compare and consisted of a relatively small number of patients. CONCLUSIONS: Crystalized phenol treatment combined with endoscopic pilonidal sinus treatment was safe, tolerable, and achieved fast and durable healing with no recurrence over an average of 22 months of follow-up.

Depigmentation Therapies for Vitiligo.

The general goals of medical management of vitiligo are to repigment vitiliginous areas of skin and to stabilize the progression of depigmentation. However, for some patients with vitiligo affecting extensive body surface areas who are unresponsive to repigmentation therapies, depigmentation of the remaining normal skin may be a better choice. Candidates for depigmentation therapy should be carefully screened and patient education is essential. Permanent topical therapies used for depigmentation include monobenzyl ether of hydroquinone, 4-methoxyphenol, and 88% phenol. Physical modalities, such as cryotherapy and lasers, are also being used successfully.

Phenol Injection Versus Excision With Open Healing in Pilonidal Disease: A Prospective Randomized Trial.

BACKGROUND: Minimally invasive procedures may be an alternative to surgical excisions for pilonidal disease. OBJECTIVE: The aim of the study was to compare phenol injection versus excision with open healing technique. DESIGN: This is a prospective randomized study (ACTRN12612000868886). SETTINGS: This study was conducted at the Ankara University and Ufuk University Departments of Surgery. PATIENTS: One hundred forty patients were randomly assigned to phenol injection (n = 70) or excision with open healing (n = 70). MAIN OUTCOME MEASURES: The primary end point of the study was the time to complete wound healing. Secondary end points were visual analog scale pain score, painkiller intake, time to resume daily activities, recurrence rate, Short Form 36 Health Survey, and Nottingham Health Profile at 3 weeks after surgery. RESULTS: Time to complete wound healing (16.2 ± 8.7 versus 40.1 ± 9.7 days) was significantly in favor of the phenol injection group (p < 0.001). The median operation time was 14.0 ± 3.8 minutes in the phenol group versus 49.0 ± 24.2 minutes in the excision with open healing group (p < 0.001). The time to resume daily activities (pain-free mobilization and defecation) was 0.8 ± 2.8 and 16.2 ± 12.6 hours after phenol injection and 9.3 ± 10.0 and 22.5 ± 15.1 hours after the excision with open healing treatment (p < 0.001, p = 0.008). Visual analog pain score at 48 hours and painkiller intake within 48 hours were significantly in favor of the phenol injection group. At the mean follow-up of 39.2 ± 9.0 months after surgery, no differences were seen in the recurrence rate between the treatment arms (13 recurrences in phenol vs 9 in excision with open healing; p = not significant). Short Form 36 and Nottingham Health Profile scores at 3 weeks after surgery were also in favor of phenol injection. LIMITATIONS: The present study was not double blinded, and a history of abscess drainage was significantly higher in the surgery group. CONCLUSIONS: Based on the results, we conclude that phenol injection is as effective as the excision with open healing technique.

Nutraceuticals and amyloid neurodegenerative diseases: a focus on natural phenols.

A common molecular feature of amyloid neurodegenerative diseases is the unfolding/misfolding of specific proteins/peptides which consequently become prone to aggregate into toxic assemblies and deposits that are the key histopathological trait of these pathologies. Apart from the rare early-onset familiar forms, these neurodegenerative diseases are age-associated disorders whose symptoms appear in aged people after long incubation periods. This makes the therapeutic approach particularly compelling and boosts the search for both early diagnostic tools and preventive approaches. In this last respect, natural compounds commonly present in foods and beverages are considered promising molecules, at least on the bench side. The so-called 'nutraceutical approach' suggests life-long healthy diets, particularly focusing on food molecules that are candidates to enter clinical trials as such or following a targeted molecular engineering. Natural phenols abundant in 'healthy' foods such as extra virgin olive oil, red wine, green tea, red berries and spices, appear particularly promising.

Comparative effects of different sclerosing agents used to treat rectal prolapse: an experimental study in rats.

BACKGROUND/PURPOSE: Sclerosing agents injected into the rectal submucosal area produce an inflammatory response and scar that prevent rectal prolapse. This study aimed to investigate the histopathological changes following submucosal injection of different sclerosing agents in rats. METHODS: Rats (n=35) were divided into control, sham, and five experimental groups, each treated with a different sclerosing agent: cow's milk, 30% saline solution, 30% dextrose solution, 70% ethyl alcohol, and 5% phenol in almond oil (PAO). All agents were injected into the submucosal area. After 4 weeks, all animals were sacrificed. Histopathological evaluation was performed according to a semi-quantitative fibrosis scoring system (grades 0 to 3), by using Masson trichrome and hematoxylin and eosin staining. RESULTS: Histopathological changes in the 5% phenol in almond oil group were significantly different from other groups (p=0.0001). Prominent submucosal fibrosis (grade 3), lymphatic vascular dilation, foreign body reaction, and lipogranuloma were observed in the 5% PAO group (p=0.007). No significant histopathological differences were seen between the 30% saline, 30% dextrose, and 70% ethyl alcohol groups. Significantly increased mucosal fibroblast proliferation (grade 2) was seen in 60% rats of the 30% dextrose group (p=0.026). The cow's milk and ethyl alcohol groups had mucosal erosions and congestion (grade 1) which were significantly different from the control group (p=0.024). No statically significant difference was observed between the 30% saline group and the control group. CONCLUSIONS: In this study we showed that 5% PAO can induce some histopathological changes in the submucosal area that increase the mucosal tightness of the mucosa, which are necessary for the treatment of rectal prolapse.

Utilisation de la prolothérapie dans le traitement des affections musculosquelettiques chroniques / Use of prolotherapy in the treatment of chronic musculoskeletal disorders

Au Canada, les maladies musculosquelettiques constituent un problème important de santé publique. Nombreuses sont les personnes qui en souffrent et doivent être traitées pour soulager leur douleur et améliorer leur état fonctionnel. Mais rares sont les traitements efficaces et sécuritaires pour les personnes atteintes. Certains suggèrent la prolothérapie comme solution thérapeutique. Cette pratique médicale consiste en l'injection de diverses substances (dextrose, glycérine et phénol) à l'intérieur des ligaments ou des tendons endommagés entraînant une irritation et une inflammation locales et permettant de stimuler la croissance cellulaire et de réparer les tissus. Actuellement, ce traitement n'est pas reconnu au Québec et, afin d'assurer une pratique médicale sécuritaire, le Collège des médecins du Québec a demandé à l'Institut national d'excellence en santé et en services sociaux (INESSS) d'évaluer l'efficacité et l'innocuité de la prolothérapie dans le traitement des douleurs musculosquelettiques chroniques. L'INESSS a retenu treize essais contrôlés randomisés (ECR) ­ dont la qualité varie de mauvaise à très bonne ­ (et cinq études observationnelles) évaluant l'efficacité de la prolothérapie sur différentes affections musculosquelettiques: 1. la lombalgie; 2. la douleur chronique du poignet; 3. l'arthrose des doigts; 4. la tendinite achiléenne; 5. la maladie d'Osgood-Schlatter; 6. l'arthrose du genou; 7. l'épicondylite latérale; 8. la subluxation temporo-mandibulaire. L'analyse des articles nous permet de constater différentes disparités dans cette pratique médicale. La composition des injections de prolothérapie dans les essais contrôlés randomisés semble dépendre des préférences de l'investigateur. Le protocole d'intervention de la prolothérapie est également très variable : il n'y a pas de normalisation pour le nombre de traitements, le nombre de sites, l'intervalle entre les traitements, la durée du traitement et les co-interventions. L'évaluation des articles scientifiques sur la prolothérapie permet à l'INESSS de conclure ce qui suit: -l'identification de la source de la douleur, essentielle dans le traitement des affections musculosquelettiques, et particulièrement des lombalgies, est absente des études; -la prolothérapie telle que pratiquée dans les études analysées n'est pas supérieure à une injection de solution saline sans agent proliférant dans le traitement des lombalgies chroniques; -pour les sept autres applications évaluées seulement dans un ou deux essais contrôlés randomisés chacun, le niveau de preuve ne permet pas de prouver ni de réfuter l'efficacité de la prolothérapie, les données étant trop fragmentaires sur ces sujets; -la prolothérapie peut avoir des conséquences graves s'il y a une injection accidentelle dans l'espace rachidien. L'absence de contrôle du site effectif d'injection par une technique d'imagerie, dans les études recensées, peut expliquer en partie la fréquence observée de ces effets indésirables; - les preuves ne soutiennent pas l'utilisation de la prolothérapie pour les affections musculosquelettiques; -l'absence d'un mécanisme d'action de la prolothérapie démontré expérimentalement ne permet pas, à l'heure actuelle, de justifier la poursuite d'études sur des sujets humains.(AU)

Musculoskeletal disorders represent a major public health problem in Canada. Many people are affected and require long-term treatments in order to relieve their pain and improve their functional status. Many of these treatments have doubtful or unknown effectiveness and safety, among which prolotherapy has been suggested as a therapeutic option. Prolotherapy consists in injecting various substances (dextrose, glycerin and phenol) into painful ligaments or tendons, with the theory that this would lead to local irritation, inflammation and stimulation of cell growth and tissue repair. Currently, this treatment is not recognized in Québec. Concerned with the safety of the public, the Collège des médecins du Québec has asked the Institut national d'excellence en santé et en services sociaux (INESSS) to evaluate the efficacy and safety of prolotherapy in the treatment of chronic musculoskeletal pain. INESSS selected 13 randomized controlled trials (RCTs) whose quality ranges from poor to very good (and five observational studies) that evaluated the efficacy of prolotherapy in different musculoskeletal conditions: 1) low back pain; 2) wrist pain; 3) finger osteoarthritis; 4) Achilles tendinosis; 5) Osgood-Schlatter disease; 6) knee osteoarthritis; 7) lateral epicondylosis; and 8) temporomandibular joint subluxation. The analysis of information provided by these studies revealed great variations with this medical procedure. For instance, the content of the prolotherapy injections in the randomized clinical trials seemed to depend on the investigator's preferences rather than on the diagnosis. Variations in treatment protocols were observed with the number of treatments, the number of sites, the interval between treatments, the duration of treatment or the co-interventions, signaling an evident lack of standardization. From the evaluation of the scientific evidence on prolotherapy, INESSS concludes: • that the origin of the pain, essential in determining a diagnosis and treatment plan when treating musculoskeletal conditions, is not mentioned in any of these studies; -that prolotherapy, as performed in the studies that were analyzed, is not superior to injecting a saline solution with no proliferative agent (placebo) for treating chronic low back pain; -that for the other seven applications of interest, each of which was evaluated in only one or two randomized controlled trials, the level of evidence does not support or refute the efficacy of prolotherapy, information being too fragmentary at this time; -that prolotherapy can have serious consequences, particularly in low-back pain patients with accidental injection into the spinal canal, as prolotherapy has not been performed in clinical studies under any type of medical imaging guidance; -that the balance between potential benefits and risks does not support the use of prolotherapy for musculoskeletal conditions; -that continuing to conduct studies on prolotherapy involving human subjects can be considered unethical given that there is an absence of scientific basis to the alleged mechanism of action for prolotherapy which remain speculative at best.(AU)

The efficacy of chemical adjuvants on giant-cell tumour of bone. An in vitro study.

Various chemicals are commonly used as adjuvant treatment to surgery for giant-cell tumour (GCT) of bone. The comparative effect of these solutions on the cells of GCT is not known. In this study we evaluated the cytotoxic effect of sterile water, 95% ethanol, 5% phenol, 3% hydrogen peroxide (H(2)O(2)) and 50% zinc chloride (ZnCI(2)) on GCT monolayer tumour cultures which were established from six patients. The DNA content, the metabolic activity and the viability of the cultured samples of tumour cells were assessed at various times up to 120 hours after their exposure to these solutions. Equal cytotoxicity to the GCT monolayer culture was observed for 95% ethanol, 5% phenol, 3% H(2)O(2) and 50% ZnCI(2). The treated samples showed significant reductions in DNA content and metabolic activity 24 hours after treatment and this was sustained for up to 120 hours. The samples treated with sterile water showed an initial decline in DNA content and viability 24 hours after treatment, but the surviving cells were viable and had proliferated. No multinucleated cell formation was seen in these cultures. These results suggest that the use of chemical adjuvants other than water could help improve local control in the treatment of GCT of bone.

Phenol-croton oil peel: establishing an animal model for scientific investigation.

BACKGROUND: Phenol-croton oil formulas for facial peeling contain a mixture of phenol, croton oil, hexachlorophene foam (Septisol; Steris Corp., Mentor, OH), and water. For years, it was felt that the active ingredient of the solution was phenol, with the view that croton oil was little more than an irritant. Hetter reported, based on clinical experience, that the addition of tiny amounts of croton oil to any concentration of phenol caused a deeper peel. He also noted that the number of applications of a phenol-croton oil solution also enhanced the peel effects. To date, there have been no animal studies that confirm these clinical observations. OBJECTIVE: The purpose of this study was to develop an animal model to further evaluate and refine the hypotheses of Hetter regarding the croton oil solution. METHODS: At the Medical College of Wisconsin, Milwaukee, WI, using a porcine animal model, 40 different solutions of phenol, water, croton oil, hexachlorophene foam, and ethyl alcohol, in 8 groupings, were applied to the flank according to grids. On days 1, 8, and 22, clinical observations were made and punch biopsies were obtained from all grids, including controls. All tissue samples were examined by a blinded dermatopathologist. RESULTS: The results were analyzed by both clinical and histologic observation. Solutions with any amount of croton oil added had a brisker inflammatory response than solutions without croton oil. The histologic examination of skin biopsies from the phenol-treated cells (with or without croton oil) demonstrated formation of sharply demarcated dermis with parallel collagen fiber bundles arranged horizontally when compared with the elastotic dermis of the control specimens. The depth of peel and time needed for healing were greater with 45 strokes than with 20 or 5 strokes. Replacing water with ethyl alcohol produced a less clinically significant peel. CONCLUSIONS: Phenol peels more deeply with increasing concentrations. Peel depth increases with increasing concentration of croton oil. Multiple applications of croton oil in phenol increases the depth of peel. The porcine model is a satisfactory model for studying chemoexfoliative agents.

High-resolution ultrasound and magnetic resonance imaging to document tissue repair after prolotherapy: a report of 3 cases.

High-resolution ultrasound imaging of musculoskeletal tissue is increasing in popularity because of patient tolerability, low cost, ability to visualize tissue in real-time motion, and superior resolution of highly organized tissue such as a tendon. Prolotherapy, defined as the injection of growth factors or growth factor production stimulants to grow normal cells or tissue, has been a controversial procedure for decades; it is currently gaining in popularity among physiatrists and other musculoskeletal physicians. This report describes imaging of tendons, ligaments, and medial meniscus disease (from trauma or degeneration). Although these tissues have been poorly responsive to nonsurgical treatment, it is proposed that tissue growth and repair after prolotherapy in these structures can be documented with ultrasound and confirmed with magnetic resonance imaging. Directions for future research application are discussed.

Alternative surgical treatment for giant-cell reparative granuloma in the metacarpal, using phenol and ethanol adjuvant therapy.

Giant-cell reparative granuloma (GCRG) or a solid variant of an aneurysmal bone cyst (ABC) is an uncommon benign reactive lesion with a predilection for the small tubular bones of the hands and feet. Treatment usually involves wide resection or amputation because of unacceptable high recurrence rates after curettage. Adjuvant therapy usually is applied to reduce the recurrence of locally aggressive bone tumors. We report 2 cases of GCRG that were treated successfully with curettage, adjuvant phenol and ethanol, and autogenous bone grafting.

[Pain originating from the abdominal wall: a forgotten diagnostic option]. / Dolor originado en la pared abdominal: una alternativa diagnóstica olvidada.

Chronic abdominal pain is a common clinical problem in primary care, and is usually referred to gastroenterologists or general surgeons. Although up to 20% of cases of idiopathic abdominal pain arise in structures of the abdominal wall, this is frequently overlooked as a possible cause. It includes pain arising from structures of the abdominal wall including skin, parietal peritoneum, cellular subcutaneous tissue, aponeuroses, abdominal muscles and somatosensorial innervation from lower dorsal roots. The diagnosis is based on anamnesis and physical examination. Carnett's sign is a simple maneuver that discriminates between parietal and visceral pain. Management with topical anesthesia is effective in a majority of patients and can help to confirm the diagnosis.

[Endodontic treatment of gangrenous teeth--literature review]. / A gangrénás fogak endodontial kezelése (lrodalmi összefoglaló).

This overview was put together to update the endodontic knowledge of the general practitioners. Several treatment methods sometimes with contradicting principles are applied in Hungary using a wide range of endodontic medicines. The aim of the paper was not only to clarify the basic therapeutic principles but also to provide practical information about the relevant endodontic products for the everyday use.

An examination of the phenol-croton oil peel: Part II. The lay peelers and their croton oil formulas.

From the turn of the century, lay face peelers, known as "skinners," ran "beautifier" salons. Beginning in the 1920s, lay peelers were using croton oil-phenol formulas in Hollywood. These persons were renowned, made a good living, and treated many, if not most, of the leading "stars" of the day. They had a treatment, a "secret," that physicians did not. Physicians brought their own wives to the peelers for their expertise. The leading lay peel personalities from the 1920s through to our time are presented. The lay peelers dominated the field until the 1960s, when legal attacks on them, often directly instigated by the newly educated physician peelers, put them at a legal disadvantage. Nevertheless, there was considerable interaction with many plastic surgeons along the way. Some plastic surgeons came into possession of the techniques and some also into knowledge of the ingredients in a formula. The author has presented the recipes of four of the renowned lay peelers, two from Hollywood, Gradé and Kelsen, and two from Miami, Coopersmith and Maschek. These recipes all have 80 to 90 percent less croton oil than the "classic" Baker formula and, therefore, wound less deeply. The Hollywood formulas were used on many celebrities both inside and outside the film world from the 1920s to the early 1990s. These lay recipes are cumbersome to prepare. The author has simplified the preparation of these lay recipes by using USP liquid phenol instead of crystals. These simple formulas are provided in a table and are as easy to prepare as the Baker formula.