4 CLINICAL PARTICULARS 4.1 Therapeutic Indications Trimetazidine is indicated in adults as add-on therapy for the symptomatic treatment of patients with stable angina pectoris who are inadequately controlled by or intolerant to first-line antianginal therapies. 4.2 Posology and method of administration Oral administration. Posology The dose is one tablet of 35mg of trimetazidine twice daily during meals. Special populations Renal impairment In patients with moderate renal impairment (creatinine clearance [30-60] ml/min) (see sections 4.4 and 5.2), the recommended dose is 1 tablet of 35mg in the morning during breakfast. Elderly Elderly patients may have increased trimetazidine exposure due to age-related decrease in renal function (see section 5.2). In patients with moderate renal impairment (creatinine clearance [30-60] ml/min), the recommended dose is 1 tablet of 35mg in the morning during breakfast. Dose titration in elderly patients should be exercised with caution (see section 4.4). Health Products Regulatory Authority

Summary of product characteristics

https://www.cell.com/trends/immunology/pdf/S1471-4906(09)00005-2.pdf

AMPed up immunity: how antimicrobial peptides have multiple roles in immune defense

Atopic dermatitis (AD) is an important chronic or relapsing inflammatory skin disease that often precedes asthma and allergic disorders. New insights into the genetics and pathophysiology of AD point to an important role of structural abnormalities in the epidermis as well as immune dysregulation not only for this skin disease but also for the development of asthma and allergies. Patients with AD have a unique predisposition to colonization or infection by microbial organisms, most notably Staphylococcus aureus and herpes simplex virus. Measures directed at healing and protecting the skin barrier and addressing the immune dysregulation are essential in the treatment of patients with AD, and early intervention may improve outcomes for both the skin disease as well as other target organs.

/pdf/atopic-dermatitis-a-disease-of-altered-skin-barrier-and-1qep0m9qxd.pdf

Atopic Dermatitis: A Disease of Altered Skin Barrier and Immune Dysregulation

GH and IGF-I are important regulators of bone homeostasis and are central to the achievement of normal longitudinal bone growth and bone mass. Although GH may act directly on skeletal cells, most of its effects are mediated by IGF-I, which is present in the systemic circulation and is synthesized by peripheral tissues. The availability of IGF-I is regulated by IGF binding proteins. IGF-I enhances the differentiated function of the osteoblast and bone formation. Adult GH deficiency causes low bone turnover osteoporosis with high risk of vertebral and nonvertebral fractures, and the low bone mass can be partially reversed by GH replacement. Acromegaly is characterized by high bone turnover, which can lead to bone loss and vertebral fractures, particularly in patients with coexistent hypogonadism. GH and IGF-I secretion are decreased in aging individuals, and abnormalities in the GH/IGF-I axis play a role in the pathogenesis of the osteoporosis of anorexia nervosa and after glucocorticoid exposure.

/pdf/growth-hormone-insulin-like-growth-factors-and-the-skeleton-48qvgpxetz.pdf

Growth Hormone, Insulin-Like Growth Factors, and the Skeleton

There are remarkable differences in the diagnostic and therapeutic management of atopic dermatitis practiced by dermatologists and pediatricians in different countries. Therefore, the European Academy of Allergy and Clinical Immunology and the American Academy of Allergy, Asthma and Immunology nominated expert teams who were given the task of finding a consensus to serve as a guideline for clinical practice in Europe as well as in North America. The consensus report is part of the PRACTALL initiative, which is endorsed by both academies.

https://www.jacionline.org/article/S0091-6749(06)00925-0/pdf

Diagnosis and treatment of atopic dermatitis in children and adults: European Academy of Allergology and Clinical Immunology/American Academy of Allergy, Asthma and Immunology/PRACTALL Consensus Report

Background
The ever-expanding range of dermal filler products for aesthetic soft tissue augmentation is of benefit for patients and physicians, but as indications and the number of procedures performed increase, the number of complications will likely also increase.

/pdf/dermal-fillers-in-aesthetics-an-overview-of-adverse-events-4kzmt9ht4j.pdf

Dermal fillers in aesthetics: an overview of adverse events and treatment approaches

Background The cathelicidin family of antimicrobial peptides is an integral component of the innate immune response that exhibits activity against bacterial, fungal, and viral pathogens. Eczema herpeticum (ADEH) develops in a subset of patients with atopic dermatitis (AD) because of disseminated infection with herpes simplex virus (HSV). Objective This study investigated the potential role of cathelicidins in host susceptibility to HSV infection. Methods Glycoprotein D was measured by means of real-time RT-PCR as a marker of HSV replication in skin biopsy specimens and human keratinocyte cultures. Cathelicidin expression was evaluated in skin biopsy specimens from patients with AD (n = 10) without a history of HSV skin infection and from patients with ADEH (n = 10). Results The cathelicidin peptide LL-37 (human cathelicidin) exhibited activity against HSV in an antiviral assay, with significant killing (P Conclusion This study demonstrates that the cathelicidin peptide LL-37 possesses antiviral activity against HSV and demonstrates the importance of variable skin expression of cathelicidins in controlling susceptibility to ADEH. Additionally, serum IgE levels might be a surrogate marker for innate immune function and serve as a biomarker for which patients with AD are susceptible to ADEH. Clinical implications A deficiency of LL-37 might render patients with AD susceptible to ADEH. Therefore increasing production of skin LL-37 might prevent herpes infection in patients with AD.

/pdf/cathelicidin-deficiency-predisposes-to-eczema-herpeticum-2gwvh7yx9s.pdf

Cathelicidin deficiency predisposes to eczema herpeticum.

Rejuvenative procedures of the face are increasing in numbers, and a plethora of different therapeutic options are available today. Every procedure should aim for the patient's safety first and then for natural and long-lasting results. The face is one of the most complex regions in the human body and research continuously reveals new insights into the complex interplay of the different participating structures. Bone, ligaments, muscles, fat, and skin are the key players in the layered arrangement of the face. Aging occurs in all involved facial structures but the onset and the speed of age-related changes differ between each specific structure, between each individual, and between different ethnic groups. Therefore, knowledge of age-related anatomy is crucial for a physician's work when trying to restore a youthful face. This review focuses on the current understanding of the anatomy of the human face and tries to elucidate the morphological changes during aging of bone, ligaments, muscles, and fat, and their role in rejuvenative procedures.

/pdf/the-anatomy-of-the-aging-face-a-review-jq7l89ju1n.pdf

The Anatomy of the Aging Face: A Review.

Background Due to its strong water-binding potential, hyaluronic acid (HA) is a well-known active ingredient for cosmetic applications. Native HA is proposed to help the skin to retain and maintain elasticity, turgor and moisture. Objective To observe the efficacy of topical application of 0.1% hyaluronan formulations of different molecular weights (MW) (50, 130, 300, 800 and 2000 kDa, respectively) in the periocular area as anti-wrinkle treatment. Material and methods Seventy-six female subjects between 30 and 60 years of age with clinical signs of periocular wrinkles applied one of the formulations twice-daily to the area of interest in a randomized fashion for 60 days. Around the other eye, a vehicle control cream was applied. Measurements of skin hydration and skin elasticity were performed before treatment, 30 and 60 days thereafter. At similar time points negative replicas were taken and evaluated by semi-automated morphometry. Results All HA-based creams utilized in this study demonstrated a significant improvement in skin hydration and overall elasticity values (R2) when compared to placebo. Measurements of wrinkle depth using mean roughness (Ra) and maximum roughness (Rz) values revealed significant improvement in the 130 and the 50 kDa HA group after 60 days of treatment compared to placebo-treated area. Conclusion Topical application of all 0.1% HA formulations used in this study led to significant improvement in skin hydration and elasticity. Application of low-molecular-weight (LMW) HA was associated with significant reduction of wrinkle depth, which may be due to better penetration abilities of LMW HA.

Efficacy of cream-based novel formulations of hyaluronic acid of different molecular weights in anti-wrinkle treatment.

Background The ever-expanding range of dermal filler products for aesthetic soft tissue augmentation is of benefit for patients and physicians, but as indications and the number of procedures performed increase, the number of complications will likely also increase. Objective To describe potential adverse events associated with dermal fillers and to provide structured and clear guidance on their treatment and avoidance. Methods Reports of dermal filler complications in the medical literature were reviewed and, based on the publications retrieved and the authors' extensive experience, recommendations for avoiding and managing complications are provided. Results Different dermal fillers have widely varying properties, associated risks, and injection requirements. All dermal fillers have the potential to cause complications. Most are related to volume and technique, though some are associated with the material itself. The majority of adverse reactions are mild and transient, such as bruising and trauma-related edema. Serious adverse events are rare, and most are avoidable with proper planning and technique. Conclusion For optimum outcomes, aesthetic physicians should have a detailed understanding of facial anatomy; the individual characteristics of available fillers; their indications, contraindications, benefits, and drawbacks; and ways to prevent and avoid potential complications.

Tatjana Pavicic

Papers

Dermal fillers in aesthetics: an overview of adverse events and treatment approaches

Cathelicidin deficiency predisposes to eczema herpeticum.

The Anatomy of the Aging Face: A Review.

Efficacy of cream-based novel formulations of hyaluronic acid of different molecular weights in anti-wrinkle treatment.

Dermal fillers in aesthetics: an overview of adverse events and treatment approaches.