Prefrontal cortex neurons encode ambient light intensity differentially across regions and layers.

While light can affect emotional and cognitive processes of the medial prefrontal cortex (mPFC), no light-encoding was hitherto identified in this region. Here, extracellular recordings in awake mice revealed that over half of studied mPFC neurons showed photosensitivity, that was diminished by inhibition of intrinsically photosensitive retinal ganglion cells (ipRGCs), or of the upstream thalamic perihabenular nucleus (PHb). In 15% of mPFC photosensitive neurons, firing rate changed monotonically along light-intensity steps and gradients. These light-intensity-encoding neurons comprised four types, two enhancing and two suppressing their firing rate with increased light intensity. Similar types were identified in the PHb, where they exhibited shorter latency and increased sensitivity. Light suppressed prelimbic activity but boosted infralimbic activity, mirroring the regions' contrasting roles in fear-conditioning, drug-seeking, and anxiety. We posit that prefrontal photosensitivity represents a substrate of light-susceptible, mPFC-mediated functions, which could be ultimately studied as a therapeutical target in psychiatric and addiction disorders.

Topical liposomal amphotericin B gel treatment for cutaneous leishmaniasis caused by Leishmania major: a double-blind, randomized, placebo-controlled, pilot study.

BACKGROUND: Cutaneous leishmaniasis (CL) topical treatments may have low efficacy, while systemic treatments have adverse effects (AEs) and high cost. Since treatment options for CL nowadays have numerous disadvantages, an alternative topical treatment is vastly needed. We assessed liposomal amphotericin B gel (LAmB gel) treatment efficacy and safety. METHODS: A randomized, double-blind, placebo-controlled trial. Adults with CL (PCR proven, ≤5 lesions) were randomized for 28 days with LAmB gel (cases) versus placebo gel (controls), followed by LAmB gel for 28 days (both groups). Lesion size, ulceration, induration, scarring, swelling, and AEs (pain, itch, erythema, discharge, fever, and urticaria) were assessed at days 1, 28, and 56. PCR was repeated at day 56. RESULTS: Thirteen patients (four cases, nine controls) with 39 lesions (11 cases, 28 controls) caused by Leishmania major (L. major) were randomized. Ulcer, induration, scarring, and swelling were noted in 18%, 91%, 0%, and 27% of cases, respectively, versus 86%, 89%, 7%, and 54% of controls, respectively. At day 28, improvement rates were low in both groups. Induration improved comparing LAmB gel treatment for 56 days versus 28 days. Ulceration, induration, and swelling improved comparing all patients at 56 days versus 28 days. PCR turned negative in three of four cases and eight of nine controls. Mild, only local, AEs were reported in <30% of the patients. CONCLUSIONS: LAmB gel is safe and may be considered as an alternative topical treatment for CL caused by L. major. Further, larger-scale studies are warranted to evaluate the long-term impact of LAmB gel on the management of CL.

A review of combined treatments for melasma involving energy-based devices and proposed pathogenesis-oriented combinations.

BACKGROUND: Melasma is an acquired disorder of hyperpigmentation, affecting a million individuals worldwide. Energy-based devices (EBDs) employed to treat melasma include various types of lasers, intense pulsed light (IPL), and radiofrequency (RF). Recent studies have attempted to address recalcitrant and recurring melasma by combining energy-based devices with topical or oral medications. OBJECTIVE: This article reviews EBDs-based augmented treatment for melasma and suggests practical pathogenesis-oriented treatment regimens. Treatment algorithms are proposed to address various components of melasma. METHODS: A systematic PubMed search was conducted acquiring information from various studies on combination treatments of melasma involving EBDs. RESULTS: The 286 retrieved articles were filtered by title to contain at least one type of energy-based modality such as laser, IPL, or RF along with at least one other treatment method. Based on their subject matter, combinations were further categorized into the subheadings: laser plus medication, laser plus laser, and IPL- and RF-containing treatment methods. CONCLUSION: There are many energy-based combination treatments that have been explored for mitigation of melasma including laser therapy with medication, multi-laser therapies, IPL, RF, and microneedling devices. Melasma is an exceedingly difficult condition to treat, however, choosing the appropriate tailor-made treatment combination can improve the final outcome.

The pathogenesis of melasma and implications for treatment.

BACKGROUND: Melasma is a complex and poorly understood disorder, with high rates of treatment failure and recurrences. OBJECTIVES: We aimed to review the current knowledge of the pathogenesis of melasma and apply this knowledge to clinical implications on relevant therapeutic interventions. METHODS: A systematic PubMed search was performed using the search term "((melasma[Text Word]) OR facial melanosis[Text Word]) AND (pathogenesis OR causality[MeSH Terms])" for articles published between 1990 and 2020. Included articles were then evaluated by two authors and assessed for relevant pathomechanistic pathways, after which they were divided into groups with minimal overlap. We then reviewed current treatment modalities for melasma and divided them according to the involved pathomechanistic pathway. RESULTS: A total of 309 search results were retrieved among which 76 relevant articles were identified and reviewed. Five main pathomechanisms observed in melasma were identified: (1) melanocyte inappropriate activation; (2) aggregation of melanin and melanosomes in dermis and epidermis; (3a) increased mast cell count and (3b) solar elastosis; (4) altered basement membrane; and (5) increased vascularization. Treatment modalities were then divided based on these five pathways and detailed in 6 relevant tables. CONCLUSION: The pathophysiology of melasma is multifactorial, resulting in treatment resistance and high recurrence rates. This wide variety of pathomechanisms should ideally be addressed separately in the treatment regimen in order to maximize results.

Comment on Casiraghi et al. "Mucoadhesive Budesonide Formulation for the Treatment of Eosinophilic Esophagitis" 2020, 12, 211.

In their article, Casiraghi, A. et al. describe a few relevant methods to assess the quality of a pharmaceutical preparation of oral viscous budesonide, intended to be swallowed, and treat the esophagus in eosinophilic esophagitis patients. They choose the following methods for this purpose: rheological properties, syringeability, mucoadhesiveness, and in vitro penetration of budesonide in porcine esophageal tissue. At the end of the article, they concluded that the best formulation of oral viscous budesonide was the one already being used in hospitals, based on xanthan gum. In their article, the authors did not emphasize that this specific formula was developed by the compounding pharmacist Eyal Zur from Israel and was published eight years before, as part of an article in the International Journal of Pharmaceutical Compounding. The purpose of this comment is to give the appropriate credit to the pharmacist who first developed and published this well designed formulation.

Enhanced Percutaneous Delivery of Beta-Blockers Using Thermal Resurfacing Drug Delivery System for Topical Treatment of Infantile Hemangiomas.

BACKGROUND: Infantile hemangiomas (IHs) are the most common vascular tumors in children. In the past few years, topical beta-blockers (bBs) have been reported to be an effective treatment of superficial IHs. OBJECTIVE: We sought to evaluate the clinical effectiveness and safety profile of enhanced percutaneous delivery of bBs for the treatment of IH. METHODS: A retrospective study of all cases of IHs treated with enhanced percutaneous delivery of bBs between 2018 and 2019 was performed. Epidemiologic, clinical, and treatment data, including effectiveness score and safety, were reviewed. RESULTS: The study included 11 patients with a total of 11 IHs. Of the total number of IHs, 7 (63.7%) showed a good response to treatment and 4 (36.3%) had a partial response; thus all patients (100%) had good or partial response to treatment. No systemic or local adverse effects were reported. LIMITATIONS: This is an uncontrolled retrospective study. CONCLUSION: Enhanced percutaneous delivery of bBs is a safe and efficient topical therapy for IH.

Thermomechanical Ablation-Assisted Photodynamic Therapy for the Treatment of Acne Vulgaris. A Retrospective Chart Review of 30 Patients.

BACKGROUND AND OBJECTIVES: Acne vulgaris, a chronic inflammatory disease, affects more than 90% of teenagers. The first-line treatments for acne vulgaris are topical and oral medications, mainly antibiotics and retinoids. However, antibiotic resistance of Propionibacterium acnes, contraindications, partial response, significant adverse effects, or recurrence creates demand for novel treatment options in acne. Aminolevulinic acid (ALA) photodynamic therapy (PDT) is a well-established modality in the treatment of acne. Nevertheless, PDT has limitations: it may not be effective for every patient; several treatments are usually required to achieve sufficient outcome; incubation time is 1-3 hours; treatment pain and post-treatment downtime may be difficult for some patients to endure; and adverse effects may occur. This retrospective chart review was conducted to evaluate the efficacy and safety of PDT, assisted by a thermomechanical ablation (TMA) fractional injury device in the treatment of patients with moderate to severe acne. STUDY DESIGN/MATERIALS AND METHODS: We conducted a retrospective chart review of 30 acne patients treated with TMA immediately before 5% ALA application with an incubation time of 1 hour and exposure to 60 J/cm2 red light (630 nm). Patients received up to three monthly treatments and were followed for 16 weeks. Two independent investigators evaluated the subject outcomes according to high definition photographs taken at baseline, before each treatment and at follow-up visits. Three acne grading methods were used: Acne Grading Scoring System (AGSS), the Leeds revised acne grading system, and the general response to the treatment score. Patients also provided self-assessments of improvement using the patient global impression of change (PGIC). RESULTS: Compared with baseline, the AGSS has showed a statistically significant reduction of 26.7% and 23.7%, respectively, at weeks 8 and 16 after final treatment. The Leeds score showed 65.2% and 60.6% improvement at the respective visits. The overall response rate was graded 3.3 ± 0.5 out of 4. PGIC score given by the patients was 5.5 out of 7, reflecting high satisfaction. CONCLUSION: TMA used immediately prior to ALA application may enhance the effectiveness of PDT in the treatment of acne with minimal side effects, reduced downtime, and fewer sessions. The exact mechanism of TMA-assisted PDT is still to be understood. Lasers Surg. Med. © 2020 Wiley Periodicals, Inc.

Low-dose Pilocarpine Spray to Treat Xerostomia.

Although pilocarpine hydrochloride tablets are currently indicated for the treatment of xerostomia, their adverse effects are frequently reported. The development of a new, low-dose pilocarpine solution for topical oral-cavity use is needed. This article discusses a few clinical trials to formulate a topical low-dose solution of pilocarpine hydrochloride for the treatment of xerostomia and presents two low dose, stable formulations of pilocarpine topical spray that can improve the patient's quality of life with minimal adverse effects.

Systematic review of natural and miscellaneous agents, for the management of oral mucositis in cancer patients and clinical practice guidelines - part 2: honey, herbal compounds, saliva stimulants, probiotics, and miscellaneous agents.

OBJECTIVE: To update the clinical practice guidelines for the management of oral mucositis (OM) that were developed by the Multinational Association of Supportive Care in Cancer/International Society of Oral Oncology (MASCC/ISOO). This part focuses on honey, herbal compounds, saliva stimulants, probiotics, and miscellaneous agents. METHODS: A systematic review was conducted by the Mucositis Study Group of MASCC/ISOO. The body of evidence for each intervention, in each clinical setting, was assigned an evidence level. The findings were added to the database used to develop the 2014 MASCC/ISOO clinical practice guidelines. Based on the evidence level, one of the following guidelines were determined: Recommendation, Suggestion, No Guideline Possible. RESULTS: A total of 78 papers were identified within the scope of this section, of which 49 were included in this review and merged with nine publications that were reported in the previous guidelines update. A new Suggestion was made for honey (combined topical and systemic delivery) for the prevention of OM in head and neck cancer patients receiving radiotherapy with or without chemotherapy. A new Suggestion clarified that chewing gum is not effective for the prevention of OM in pediatric patients with hematological or solid cancer treated with chemotherapy. No guideline was possible for other interventions. CONCLUSIONS: Numerous natural products and herbal remedies were studied for the management of OM. Of the agents reviewed in this systematic review, a guideline in favor was made for honey (combined topical and systemic), while a guideline against was made for chewing gum. Additional research is warranted to clarify the potential of other interventions.

Oral Viscous Sucralfate Gel for Post-procedural Treatment of Barrett's Esophagus.

Barrett's esophagus refers to an abnormal change in the cells of the lower portion of the esophagus. It is characterized by the replacement of the normal stratified squamous epithelium lining of the esophagus by columnar epithelium cells which are usually found lower in the gastrointestinal tract. The medical significance of this pathology is approximately 0.5% risk to develop esophageal adenocarcinoma (per patient diagnosed with Barrett's esophagus per year). Diagnosis requires endoscopy and biopsy. In general, high-grade dysplasia and early stages of adenocarcinoma can be treated by endoscopic resection and/or endoscopic ablative therapy, whereas advanced stages (submucosal) are generally advised to undergo surgical treatment. Patients who undergo endoscopic resection and/or endoscopic ablative therapy might suffer from retrosternal discomfort and transient dysphagia, adverse effects that sometimes accompanies these procedures. One of the common post-procedural treatments is sucralfate 1 g 3 to 4 times daily for two weeks after the procedure. The rational for this treatment is to enhance the wound-healing process in the esophagus tissues and to coat the wounded tissues with a cytoprotective agent. As no clinical trials have been performed in order to prove the efficacy of sucralfate in the postprocedural treatment of Barrett's esophagus, this article summarizes the clinical experience accumulated from the treatment with sucralfate as a wound-healing enhancer. In addition, the article deals with the hypothesized mechanism of action of sucralfate and gives one option for compounding sucralfate oral viscous gel.

Topical Treatment of Cutaneous Leishmaniasis in Israel, Part 3.

Cutaneous leishmaniasis is the most common form of leishmaniasis with global incidence of about 1.5 million cases annually. The disease is endemic in Israel and caused by two types, leishmania major and leishmania tropica. The two types of cutaneous leishmaniasis in Israel are not life threatening, but the multiple skin lesions developed from the contaminated sandfly bites cause significant damage to the quality of life for a few months in patients with leishmania major and sometimes for more than a year in patients with leishmania tropica. Topical treatment for this localized skin disease is very attractive although only one medication is registered in Israel (15% paromomycin +12% methylbenzethonium chloride ointment) for the topical treatment of leishmania major. Two significant disadvantages characterize this topical medication, 1) relatively low efficacy and 2) significant irritation and pain. This article represents part 3 of a 3-part article on the topic of cutaneous leishmaniasis. Part 1 discussed the treatment option of amphotericin-B liposomal gel, part 2 discussed the treatment option of paromomycin sulfate liposomal gel, and this final part (3) discusses the treatment option of photodynamic therapy.

Topical Treatment of Cutaneous Leishmaniasis in Israel, Part 2.

Cutaneous leishmaniasis is the most common form of leishmaniasis with global incidence of about 1.5 million cases annually. The disease is endemic in Israel and caused by two types, leishmania major and leishmania tropica. The two types of cutaneous leishmaniasis in Israel are not life threatening, but the multiple skin lesions developed from the contaminated sand fly bites cause significant damage to the quality of life for a few months in patients with leishmania major and sometimes for more than a year in patients with leishmania tropica. Topical treatment for this localized skin disease is very attractive although only one medication is registered in Israel (15% paromomycin +12% methylbenzethonium chloride ointment), which is for the topical treatment of "leishmania major." Two significant disadvantages characterize this topical medication, 1) relatively low efficacy and 2) significant irritation and pain, which could result in failure of the registered treatment. This article (part 2 of a 3-part article), which also includes a compounded formulation, discusses the treatment option of paromomycin sulfate liposomal gel (free of the sensitizing methylbenzethonium chloride).

Systematic review of natural and miscellaneous agents for the management of oral mucositis in cancer patients and clinical practice guidelines-part 1: vitamins, minerals, and nutritional supplements.

PURPOSE: To update the clinical practice guidelines for the use of natural and miscellaneous agents for the prevention and/or treatment of oral mucositis (OM). METHODS: A systematic review was conducted by the Mucositis Study Group of the Multinational Association of Supportive Care in Cancer / International Society of Oral Oncology (MASCC/ISOO). The body of evidence for each intervention, in each cancer treatment setting, was assigned an evidence level. The findings were added to the database used to develop the 2014 MASCC/ISOO clinical practice guidelines. Based on the evidence level, the following guidelines were determined: Recommendation, Suggestion, and No Guideline Possible. RESULTS: A total of 78 papers were identified within the scope of this section, out of which 29 were included in this part, and were analyzed with 27 previously reviewed studies. A new Suggestion was made for oral glutamine for the prevention of OM in head and neck (H&N) cancer patients receiving radiotherapy with concomitant chemotherapy. The previous Recommendation against the use of parenteral glutamine for the prevention of OM in hematopoietic stem cell transplantation (HSCT) patients was re-established. A previous Suggestion for zinc to prevent OM in H&N cancer patients treated with radiotherapy or chemo-radiotherapy was reversed to No Guideline Possible. No guideline was possible for other interventions. CONCLUSIONS: Of the vitamins, minerals, and nutritional supplements studied for the management of OM, the evidence supports a Recommendation against parenteral glutamine in HSCT patients and a Suggestion in favor of oral glutamine in H&N cancer patients for the management of OM.

Topical Treatment of Primary Focal Hyperhidrosis, Part 2.

This represents part 2 of a 2-part article on the topic of primary focal hyperhidrosis. Part 1, which was published in the International Journal of Pharmaceutical Compounding's January/February 2019 issue, provided a comprehensive review of the active pharmaceutical ingredients aluminum salts and methenamine in the treatment of primary focal hyperhidrosis. Part 2 provides a comprehensive review of the active pharmaceutical ingredients glycopyrronium salts and oxybutynin chloride in the treatment of primary focal hyperhidrosis.

Penfluridol, a Unique Psychiatric Medicine for the Treatment of Chronic Schizophrenia.

Schizophrenia is a serious, disabling, enduring, and relapsing mental illness which causes problems with the ability to think, feel, and perceive things clearly. One cause of relapse and readmission to a hospital is poor compliance with antipsychotic medication, often due to its adverse effects. Schizophrenia may also affect a person's insight, interfering with their ability to appreciate the benefit of taking medication long term. The relapse rate is significantly higher in those who have discontinued antipsychotic medication. Penfluridol is an unusual, potent, long-acting, first-generation, oral antipsychotic agent indicated for the treatment of chronic schizophrenia, acute psychosis, and Tourette syndrome. It may be considered a depot medication, as it is administered once a week. Despite this positive analysis, and the unique added value of this medication to psychotic, non-compliant patients, Janssen-Cilag, the sole manufacturer of penfluridol worldwide, decided to stop production in 2009. This decision forced many psychotic patients worldwide to abandon the once-a-week convenient treatment and to replace it with a daily, oral treatment or a depot injection. Because penfluridol is no longer commercially available, it has created an opportunity for compounding pharmacists worldwide to accept this challenge and offer this medication to psychiatrists because of its clinical therapeutics. For the past 5 years, penfluridol has been available to compounding pharmacists in Israel and has received favorable feedback from physicians and patients.

Topical Treatment of Cutaneous Leishmaniasis in Israel, Part 1.

Cutaneous leishmaniasis is the most common form of leishmaniasis with global incidence of about 1.5 million cases annually. The disease is endemic in Israel and caused by two types, Leishmania major and Leishmania tropica. The two types of cutaneous leishmaniasis in Israel are not life threatening, but the multiple skin lesions developed from the contaminated sandfly bites cause significant damage to the quality of life for a few months in patients with Leishmania major and sometimes for more than a year in patients with Leishmania tropica. The disease ends spontaneously, often with disfiguring scars. The aim of the treatment is to significantly shorten the wound-healing process, hopefully with minimal scars and with parasite eradication. Topical treatment for this localized skin disease is very attractive, although only one medication is registered in Israel (15% paromomycin +12% methylbenzethonium chloride ointment), which is for the topical treatment of "Leishmania major." Relatively low efficacy and significant irritation and pain are two significant disadvantages that characterize this topical medication and could result in failure of the registered treatment. This article, which is presented in 3 parts, discusses three options in the treatment of cutaneous leishmaniasis, 1) amphotericin B liposomal gel and 2) paromomycin sulfate liposomal gel (free of the sensitizing methylbenzethonium chloride), both of which the author considers as efficacious in the treatment of cutaneous leishmaniasis, although to confirm these claims, randomized controlled trials must be conducted, and 3) photodynamic therapy. Most of the reports claim that the photodynamic therapy can achieve results above 90% healing of wounds in a relatively short period of time and with relatively minimal scars. However, a caveat must be held since some of these studies indicate that not all healed wounds become free of the parasite. The daylight option of photodynamic therapy is an interesting modality which abolishes the need for an expensive artificial light source and expensive hospitalization time and enables ambulatory treatment to be efficacious against both types of Leishmania in Israel. Formulations are provided for the three modalities, with the third option being based on 5-aminolevulinic acid hydrochloride as the photosensitizer for this therapy.

Topical Treatment of Primary Focal Hyperhidrosis, Part 1.

Primary focal hyperhidrosis is idiopathic, localized, uncontrollable, excessive, and unpredictable sweating beyond what is necessary to regulate body temperature. Primary hyperhidrosis is thought to affect approximately 2% to 3% of the population, and its effect on a patient's quality of life is very significant. Primary focal hyperhidrosis can be managed using various therapeutic options, including drugs (topical and systemic), nonsurgical interventions (e.g., iontophoresis, botulinum toxin injections), and surgery. This article, which is presented in 2 parts, is a comprehensive review of the topical, evidence-based treatments of primary focal hyperhidrosis, and it covers the following active pharmaceutical ingredients: aluminum salts, methenamine, glycopyrronium salts, oxybutynin chloride; the latter 2 ingredients will be discussed in part 2 of this article. This article discusses the evidence-based data that exists from clinical trials that support the use of topical medications to treat the pathology from efficacy and from a safety point of view. This review also discusses compounding considerations for professionally and safely compounding various topical preparations. In addition, a range of relevant formulas are attached to the article and can be used by compounding pharmacists.

Treatment of Dermatologic Adverse Events Induced by Oncological Treatments Using Compounded Medications.

Radiotherapy and epidermal growth factor receptor inhibitors, as important representatives of current chemotherapy, are crucial and irreplaceable treatments of modern oncology. These two types of treatments frequently cause severe dose-dependent dermatologic adverse events that can negatively affect a patient's quality of life and compliance and cause inappropriate dose reductions and even treatment brakes. This article aims to emphasize new scientific data, published in peer reviews, regarding new possibilities to manage these debilitating dermatological adverse events. Since part of the scientific findings is new, the responsibility to enable pharmacologic treatment is in the compounding pharmacist domain. The article also suggests new formulations to the new pharmacologic treatment.

Topical propranolol improves epistaxis in patients with hereditary hemorrhagic telangiectasia - a preliminary report.

BACKGROUND: Severe epistaxis is often difficult to control in patients with hereditary hemorrhagic telangiectasia (HHT). Propranolol has been shown to have antiangiogenic properties in vitro and in vivo and is commonly used to treat hemangiomas. We present our experience with topical nasal propranolol for the treatment of moderate to severe epistaxis in patients with HHT. METHODS: Retrospective case series. Six patients with HHT were treated with 0.5 cm3 of 1.5% propranolol gel, applied to each nostril twice daily for at least 12 weeks. Outcome measures were epistaxis severity score (ESS), hemoglobin level, and number of blood transfusions prior to and while on treatment. Local and systemic side effects were recorded. RESULTS: The mean duration of treatment was 30 ± 5.6 weeks. A significant improvement in the ESS was found in all patients, with a mean decrease from 6.4 ± 2.1 at treatment onset to 3.5 ± 1.7 at 12 weeks (p = 0.028). Hemoglobin level increased significantly from 8.4 ± 3.1 to 11.0 ± 1.8 g/dL at 12 weeks (p = 0.043). The mean number of blood transfusions decreased from 4.5 ± 4.9 before treatment to 2.5 ± 2.9 at 12 weeks and 0.3 ± 0.8 at 24 weeks, but the difference did not reach statistical significance (p = 0.109 for both). No significant side effects of treatment were recorded. CONCLUSIONS: These preliminary results suggest that topical propranolol may be effective for the treatment of epistaxis in patients with HHT. A prospective controlled trial is required to confirm our findings.