Challenges in Optimizing Nanoplatforms Used for Local and Systemic Delivery in the Oral Cavity.

In this study, we focused on innovative approaches to improve drug administration in oral pathology, especially by transmucosal and transdermal pathways. These improvements refer to the type of microneedles used (proposing needles in the saw), to the use of certain enhancers such as essential oils (which, besides the amplifier action, also have intrinsic actions on oral health), to associations of active substances with synergistic action, as well as the use of copolymeric membranes, cemented directly on the tooth. We also propose a review of the principles of release at the level of the oral mucosa and of the main release systems used in oral pathology. Controlled failure systems applicable in oral pathology include the following: fast dissolving films, mucoadhesive tablets, hydrogels, intraoral mucoadhesive films, composite wafers, and smart drugs. The novelty elements brought by this paper refer to the possibilities of optimizing the localized drug delivery system in osteoarthritis of the temporomandibular joint, neuropathic pain, oral cancer, periodontitis, and pericoronitis, as well as in maintaining oral health. We would like to mention the possibility of incorporating natural products into the controlled failure systems used in oral pathology, paying special attention to essential oils.

Natural Sources of Therapeutic Agents Used in Skin Conditions.

Skin conditions are numerous and often have a major impact on patients' quality of life, and effective and safe treatment is very important. The conventional drugs used for skin diseases are usually corticosteroids and antimicrobial products that can induce various side effects, especially with long-term use, which is why researchers are studying alternatives, especially biologically active natural products. Three products caught our attention: bee venom (BV), due to reported experimental results showing anti-inflammatory, antibacterial, antiviral, antioxidant, antimycotic, and anticancer effects, Ficus carica (FC) due to its demonstrated antioxidant, antibacterial, and anti-inflammatory action, and finally Geranium essential oil (GEO), with proven antifungal, antibacterial, anti-inflammatory, and antioxidant effects. Following a review of the literature, we produced this paper, which presents a review of the potential therapeutic applications of the three products in combating various skin conditions and for skin care, because BV, FC, and GEO have common pharmacological actions (anti-inflammatory, antibacterial, and antioxidant). We also focused on studying the safety of the topical use of BV, FC, and GEO, and new approaches to this. This paper presents the use of these natural therapeutic agents to treat patients with conditions such as vitiligo, melasma, and melanoma, as well as their use in treating dermatological conditions in patients with diabetes.

Ceratum Galeni: An old eponym honoring Galen and his cold cream.

Ceratum Galeni is an old eponym honoring the name of Galen of Pergamum (129 to cca 216 CE) and a cold cream he described more than 1,800 years ago. We traced this eponym back to the 14th and 16th centuries in published medical texts by Guy de Chauliac (ca 1300-1368) and Andreas Vesalius (1514-1564). We also found a 4th-century reference in a medical work by Oribasius (ca 320-403 CE) to a mixture of wax and oil of roses based on Galen's cold cream formula. We present the images of a 19th-century apothecary white porcelain jar from Paris, France, on which appears the words Cerat Galeni, as well as a 20th-century oil painting by the American artist Robert Thom (1915-1979), which shows Galen administering his cold cream to a woman. Today, the composition of cold cream is formulated differently from Galen's original version, although the basic concept of cold cream as an oil and water emulsion remains the same. The widespread mention of Ceratum Galeni across the centuries and the popularity of cold creams today are striking examples of Galen's enormous influence on medicine as one of its founding fathers.

Case report: Abrikossoff's tumor of the facial skin.

Abrikossoff tumors, also known as granular cell tumors (GCT), originate from Schwann cells. The most common location is in the oral cavity, followed by the skin, but they can also be found in the breast, digestive tract, tracheobronchial tree, or central nervous system. They can affect both sexes at any age, with a higher incidence between 30 and 50 years and a slight predisposition for female sex. They are usually solitary tumors but may also be multifocal. Most of the time, they are benign, with malignancy being exceptional in <2% of cases. Clinically, they appear as solid, well-defined, painless tumors, located subcutaneously with dimensions that can reach up to 10 cm. The definitive diagnosis is based on the immunohistochemical examination, and the treatment for benign tumors consists of surgical excision. Chemotherapy or radiotherapy may be required for malignant lesions, but the treatment regimens and their benefits remain unclear. This manuscript presents the case of a 12-year-old girl with a benign GCT, located in the skin on the mandibular line.

Strategies for Improving Transdermal Administration: New Approaches to Controlled Drug Release.

In this work, we aim to address several strategies to improve transdermal drug delivery, such as iontophoresis, sonophoresis, electroporation and micron. We also propose a review of some transdermal patches and their applications in medicine. TDDs (transdermal patches with delayed active substances) are multilayered pharmaceutical preparations that may contain one or more active substances, of which, systemic absorption is achieved through intact skin. The paper also presents new approaches to the controlled release of drugs: niosomes, microemulsions, transfersomes, ethosomes, but also hybrid approaches nanoemulsions and microns. The novelty of this review lies in the presentation of strategies to improve the transdermal administration of drugs, combined with their applications in medicine, in light of pharmaceutical technological developments.

Clinical, Dermoscopic and Microscopic Features of a "Collision Tumour" Ultimately Confirmed as a Regressing Melanoma - Lessons Learnt from a Chance Diagnosis.

Spontaneous regression of malignant melanoma was first reported over a century ago. Clinically, areas of blue or grey colouration in lesions may be indicative of regression. Dermoscopy is a very useful tool for diagnosing regression. An important criterion is the blue-white scar. About 10-35% of excised melanomas show features of regression histopathologically. We present a case of regressing melanoma, with clinical and dermoscopic features suggesting a collision tumour, diagnosed histopathologically. This case might improve our knowledge of the potential clinical manifestations, and the biology, of regressing melanoma.

An integrative therapeutic approach to elephantiasis nostras verrucosa: A case report.

Elephantiasis nostras is a chronic disorder that is difficult to treat. It is characterized by marked lymphedema, associated with hyperkeratosis, ulceration, deep skin folds and a cobblestone appearance of the skin. Causes include parasitic and bacterial infections, neoplasia and obesity, but numerous cases have uncertain aetiology. Treatment includes surgery and medication, which are associated with variable results. In the present study, a 72-year old female with renal insufficiency presented with leg enlargement of 3-4 years duration, which rendered her housebound. Examination showed massive lower limb enlargement, with typical cobblestone appearance. She was on furoseminde 80 mg/day. A diagnosis of elephantiasis nostras was made. Then, she was treated with increased furosemide from 80 to 120 mg daily and homeopathic Apocynum cannabinum, CH30 potency, t.d.s. Unavailability of corresponding fit excluded the use of compressive stockings. The patient remitted over 18 months, with limb diameters dropping from 68/46 cm (right mid-calf/ankle) and 67/43 cm (left mid-calf/ankle) to 64/43 cm (right mid-calf/ankle) and 64.5/45 cm (left mid-calf/ankle) at 6 months, 63/42 cm (right mid-calf/ankle) and 65/41 cm (left mid-calf/ankle) at 12 months, and 46/35 cm (right mid-calf/ankle) and 48/36 cm (left mid-calf/ankle) at 18 months, with improvement of skin appearance. Elephantiasis nostras is not spontaneously remitting. In this resource-limited setting, furosemide combined with homeopathic Apocynum cannabinum has proved valuable and may be used for similar cases.

Orthopaedic manifestations of neurofibromatosis type 1: A case report.

Neurofibromatosis type 1 (NF1) or von Recklinghausen disease is one of the most common autosomal dominant genetic diseases. It is characterized by 'café-au-lait' spots and multiple tumors starting from the central and peripheric nervous system. The diagnosis is determined on two out of seven criteria: i) A total of 6 or more light brown spots larger than 5 mm in diameter (pre-puberty) or 15 mm in diameter (post-puberty); ii) a total of 2 or more neurofibromas or one plexiform neurofibroma; iii) axillary or inguinal freckling; iv) optic glioma; v) a total of 2 or more Lisch nodules; vi) bone abnormalities: tibia pseudarthrosis or dysplasia of the sphenoid wing; and vii) a relative of first degree having an NF1 diagnosis. A total of ~50% of patients have significant musculoskeletal manifestation, with scoliosis and congenital pseudarthrosis of tibia most common. Management of the orthopaedic manifestations of NF1 is often difficult. Due to NF1 influencing multiple organ systems, patients are likely to benefit most from a multidisciplinary treatment strategy.

Nevi, biologics for psoriasis and the risk for skin cancer: A real concern? (Case presentation and short review).

Psoriasis is a systemic inflammatory cutaneous disease that affects approximately 2% of the world's population. Systemic treatments and biologic treatment therapies are a powerful option for patients with moderate to severe psoriasis. Some studies from the literature indicate an overall small, but increased, risk of neoplasia in patients with psoriasis treated with phototherapy or systemic medication. The relationship between psoriasis and malignancy is not very well established; there are few studies with conflicting results. We present the case of a 31-year-old male patient, diagnosed with psoriasis, who was deemed eligible for systemic therapy. Treatment with methotrexate was initiated, but without a satisfactory outcome. Given the patient's resistant disease involving 15% of his body surface, his desire to have a clear skin, besides his being naïve to biologic therapy, he was proposed to start treatment with secukinumab 300 mg monthly. The patient experienced complete clearance of lesions and was followed-up on the basis of clinical and biological parameters. There are limited data concerning the relationship between melanocytic lesions, psoriasis and melanoma. Immunologic pathways implicated in psoriasis induce a reduction in the number of melanocytic nevi. Nevertheless, little is known concerning the association of melanocytic nevi with psoriasis. Thorough skin examination, meaning clinical and dermoscopic evaluation of melanocytic lesions, must be encouraged in patients treated with systemic therapies such as biologic agents.

Individualised Homeopathic Treatment of Acne-An Analysis of 83 Patients.

BACKGROUND: Acne is a common disorder of the pilosebaceous follicle. The face, back and chest are usually involved. It leads to significant diminution in quality of life. Numerous treatments are documented in therapeutic guidelines. Naturopathic approaches have been proposed in some, but the role of homeopathy is not examined. METHODS: In this study, 83 patients treated for acne with individualised homeopathic medicine alone were reviewed. Most had received conventional acne treatment, with limited success prior to presentation for homeopathy. Each patient was prescribed a single homeopathic medicine and followed up at 6- to 8-week intervals. The individualisation process resulted in 17 different medicines being used in this group. Photographic documentation was obtained per patient, with informed consent. Patients were classified as mild (comedonal acne with no papules or pustules), moderate (inflammatory and non-inflammatory lesions) and severe (predominantly inflammatory lesions: pustules, cysts, nodules). Results of treatment were recorded as remission (decrease in new lesion number, duration and intensity), failure to respond, and lost to follow-up (LTF). RESULTS: The average age of patients was 21.5 years (range 11-45 years). The F:M ratio was 55 (66.3%):28 (33.7%). Average pre-treatment duration was 5.5 years (0.25-22 years). Seven (8.4%) patients had mild acne, 37 (44.6%) moderate, and 39 (47%) severe acne. There were 13 (15.7%) LTFs, two (2.4%) failed to respond, and 68 (81.9%) went into remission. Average time to remission was 1.9 months (range 1.5-6 months), with no relapses or side-effects. The most commonly prescribed medicines were Lycopodium (38.6%), Palladium (15.7%) and Platinum (12.1%). CONCLUSION: Individualised homeopathy may be useful for acne therapy. The most useful medicines appeared to be Lycopodium, Palladium and Platinum, though 17 different medicines were used in this study, underscoring the value of individualisation of therapy, a key characteristic of homeopathy.

A Working Hypothesis on Vesicular Lesions Related to COVID-19 Infection, Koebner Phenomena Type V, and a Short Review of Related Data.

SARS-CoV-2 has recently been associated with the reactivation of varicella zoster virus in patients. This is potentially an observation of a local susceptibility of the skin in areas of vesicle formation. This article explores the dermatologic manifestations that have been linked to the SARS-CoV-2 virus, their infectious risk, as well as potential confounding factors. An isotopic response may be occurring due to the occurrence of an immunocompromised district incited by sustained inflammation mediated by inflammatory cytokines.

Chitin-lipid interactions and the potential relationship between Demodex and SARS-CoV-2.

Already from the early days of the COVID-19 pandemic, regulatory agencies have attempted to ascertain the possible routes of SARS-CoV-2 viral transmission. It is hypothesized that the lipid bilayer that surrounds the SARS-CoV-2 improves its ability to remain stable on sebum-rich skin and serves as another possible route of contracting the virus. One possible aspect of these observations that has yet to be explored in detail is what role arthropods that have been associated with human skin infestation, such as Demodecidae or Pyemotidae species, play in viral transmission. It seems likely that arthropod-coronavirus interactions may take place through the molecular attraction forces between the chitin found on the exoskeleton of mites commonly found on human skin and the lipids present on the viral envelope of the SARS-CoV-2. We believe this may mean that arthropods are currently an overlooked cofactor in viral infection which may have some important biomedical implications for both prevention and treatment.

Therapy Delayed is Therapy Denied: A Case Report of Melanoma Misdiagnosed as Diabetic Foot Ulcer.

Malignant melanoma is a deadly form of skin cancer, and prompt diagnosis is a key factor in providing adequate, life-saving therapy. A 75-year-old man, with long-standing type 2 diabetes mellitus, presented with a 2- to 3-year history of right heel ulcer. He had received various therapies for a diagnosis of diabetic foot ulcer, to no avail. Physical examination showed a black, fungating ulcerated lesion on his right heel, with minimal bleeding. No inguinal lymphadenopathy was palpated. A biopsy was done, which revealed BRAF-negative malignant melanoma, with a vertical growth phase, Breslow 3.1 mm, ulceration, 11 mitoses/mm2, Clark level IV, no lymphatic or vascular invasion observed. Right inguinal lymph node sampling suggested no involvement, but PET-CT suggested pulmonary, right inguinal lymph node and bone involvement. The patient was referred to the oncologists. Written informed consent for publication was given by the patient. Diabetic foot ulcers are a frequently encountered, but serious complication of diabetes mellitus. Delayed healing is often seen, despite adequate therapy. The differential diagnosis of diabetic foot ulcers is vast and includes neoplasia. When a foot ulcer fails to heal, other differential diagnoses must be considered, in order for the patient to receive adequate therapy. Here specialist consultations, including dermatology consultations, could improve chances of delivering the right therapy promptly. This is a factor underlying the emphasis on a multidisciplinary approach to foot ulcer therapy. Our presentation - reported according to the CARE guidelines - also illustrates the fact that failure to reach a timely diagnosis may deny the patient the opportunity to receive adequate treatment. In such cases, "delayed therapy becomes denied (or failed) therapy", paraphrasing the old adage "Justice delayed is justice denied".

Spectral forecast: A general purpose prediction model as an alternative to classical neural networks.

Here, we describe a general-purpose prediction model. Our approach requires three matrices of equal size and uses two equations to determine the behavior against two possible outcomes. We use an example based on photon-pixel coupling data to show that in humans, this solution can indicate the predisposition to disease. An implementation of this model is made available in the supplementary material.

Case series of an alternative therapy for generalised lichen planus: Four case studies.

Lichen planus (LP) is an idiopathic, cell-mediated immune disorder, accompanied by itching. Spontaneous remission occurs. Topical and systemic therapies are utilised. Four cases of generalized LP with and without mucosal involvement treated homeopathically are presented. Case 1: A 48-year-old female presented with a 7-month history of generalized itchy rash, which had been diagnosed as LP, treated unsuccessfully with topical steroids and removal of dental fillings. Examination revealed violaceous papules on upper and lower limbs, oral mucosal lesions and an irregular, erythematous, blanching, macular rash on the chest. She received homeopathic Ignatia amara at medication dilution factor (MK) potency, weekly dose and went into remission at 3 months. Patient remains in remission. Case 2: A 65-year-old female presented with a 27-year history of generalized, LP, which had been unresponsive to topical steroids. Examination showed generalized, violaceous papules, with no mucosal involvement. She received homeopathic Aurum metallicum, MK potency, weekly, and went into remission. She relapsed at 8 months after onset of therapy, following a very stressful incident, but gained remission again with Aurum metallicum after 1 month of therapy. She remains in remission. Case 3: A 38-year-old male presented with a 21-year history of generalized LP. Medical history was significant for hepatitis B and asthma. Topical steroid therapy was only partially successful. Examination revealed generalized, violaceous papules, with oral and genital involvement. He received homeopathic Lycopodium at MK potency, weekly, and remitted by 2 months. He remains in remission. Case 4: A 41-year-old male presented with a 12-year history of generalized hypertrophic LP, which had responded partially to topical steroids and ultraviolet A therapy. Medical history was significant for reduced sense of smell. Examination revealed generalized, violaceous, hypertrophic papules and nodules. He received homeopathic Carcinosinum at MK potency and remitted at 6-months. In its long-standing, generalized form, with mucosal involvement, LP may respond to individualized homeopathy. More research may clarify homeopathy's place in LP therapy.