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Pathophysiology and treatment of osteoporosis: challenges for clinical practice in older people.

Osteoporosis, a common chronic metabolic bone disease is associated with considerable morbidity and mortality. As the prevalence of osteoporosis increases with age, a paralleled elevation in the rate of incident fragility fractures will be observed. This narrative review explores the origins of bone and considers physiological mechanisms involved in bone homeostasis relevant to management and treatment. Secondary causes of osteoporosis, as well as osteosarcopenia are discussed followed by an overview of the commonly used pharmacological treatments for osteoporosis in older people.

Zoledronic acid induces antiproliferative and apoptotic effects in human pancreatic cancer cells in vitro.

Bisphosphonates (BPs) are an emerging class of drugs mostly used in the palliative care of cancer patients. We investigated the in vitro activity of the most potent antiresorptive BP, zoledronic acid (ZOL), on the growth and survival of three human pancreatic cancer (PC) cell lines (BxPC-3, CFPAC-1 and PANC-1). Pancreatic cancer frequently has a dysregulated p21(ras) pathway and therefore appears to be a suitable target for BPs that interfere with the prenylation of small GTP-binding proteins such as p21(ras). We found that ZOL induces growth inhibition (IC(50):10-50 micro M) and apoptotic dea

Patient reported outcome measures in a large cohort of patients with type 1 Gaucher disease.

BackgroundIt is now acknowledged that the input of patients in health outcome assessment is vital to understanding the impact of diseases and interventions for those diseases. This study is the first report of patient-reported outcome measures (PROM) in a large cohort of patients with type 1 Gaucher disease (GD1) enabling us to study predictors of the reported outcomes.MethodThe PROM was sent via a mobile phone survey to 405 adult patients with GD1. Demographics, clinical data, and treatment status were extracted from clinic charts. Age, sex, severity score index (SSI) at presentation and trea

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… With the introduction of disease-specific therapy for patients with GD1 in the form of enzyme replacement therapy (ERT) and substrate reduction therapy (SRT), the wellbeing of patients with GD1 has largely improved, but not without significant cost to the patient and society [ 7 , 8 ]. … Martinez-Redondo C Ortuno FJ Lozano ML Jerez A del Mar OM Giraldo P Vicente V IgM monoclonal component associated with type I Gaucher disease resolved after enzyme replacement therapy: a case report J Inherit Metab Dis 2009 32 Suppl 1 S265 267 10.1007/s10545-009-1207-8 19562501 26. …

Development and Clinical Translation of Approved Gene Therapy Products for Genetic Disorders.

The field of gene therapy is striving more than ever to define a path to the clinic and the market. Twenty gene therapy products have already been approved and over two thousand human gene therapy clinical trials have been reported worldwide. These advances raise great hope to treat devastating rare and inherited diseases as well as incurable illnesses. Understanding of the precise pathomechanisms of diseases as well as the development of efficient and specific gene targeting and delivery tools are revolutionizing the global market. Currently, human cancers and monogenic disorders are indicati

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… Current therapeutic approaches consist of hematopoietic stem cell transplantation (HSCT), Enzyme replacement therapy (ERT) as well as gene therapy tool. …

Sialyltransferase Inhibitors for the Treatment of Cancer Metastasis: Current Challenges and Future Perspectives.

Potent, cell-permeable, and subtype-selective sialyltransferase inhibitors represent an attractive family of substances that can potentially be used for the clinical treatment of cancer metastasis. These substances operate by specifically inhibiting sialyltransferase-mediated hypersialylation of cell surface glycoproteins or glycolipids, which then blocks the sialic acid recognition pathway and leads to deterioration of cell motility and invasion. A vast amount of evidence for the in vitro and in vivo effects of sialyltransferase inhibition or knockdown on tumor progression and tumor cell meta

Modulating epigenetic modifications for cancer therapy (Review).

Cancer is a global public health concern. Alterations in epigenetic processes are among the earliest genomic aberrations occurring during cancer development and are closely related to progression. Unlike genetic mutations, aberrations in epigenetic processes are reversible, which opens the possibility for novel pharmacological treatments. Non‑coding RNAs (ncRNAs) represent an essential epigenetic mechanism, and emerging evidence links ncRNAs to carcinogenesis. Epigenetic drugs (epidrugs) are a group of promising target therapies for cancer treatment acting as coadjuvants to reverse drug resist

Physiological Role and Use of Thyroid Hormone Metabolites - Potential Utility in COVID-19 Patients.

Thyroxine and triiodothyronine (T3) are classical thyroid hormones and with relatively well-understood actions. In contrast, the physiological role of thyroid hormone metabolites, also circulating in the blood, is less well characterized. These molecules, namely, reverse triiodothyronine, 3,5-diiodothyronine, 3-iodothyronamine, tetraiodoacetic acid and triiodoacetic acid, mediate both agonistic (thyromimetic) and antagonistic actions additional to the effects of the classical thyroid hormones. Here, we provide an overview of the main factors influencing thyroid hormone action, and then go on t

Revolutionizing in vivo therapy with CRISPR/Cas genome editing: breakthroughs, opportunities and challenges.

Genome editing using the CRISPR/Cas system has revolutionized the field of genetic engineering, offering unprecedented opportunities for therapeutic applications in vivo. Despite the numerous ongoing clinical trials focusing on ex vivo genome editing, recent studies emphasize the therapeutic promise of in vivo gene editing using CRISPR/Cas technology. However, it is worth noting that the complete attainment of the inherent capabilities of in vivo therapy in humans is yet to be accomplished. Before the full realization of in vivo therapeutic potential, it is crucial to achieve enhanced specific

Primary Osteoporosis Induced by Androgen and Estrogen Deficiency: The Molecular and Cellular Perspective on Pathophysiological Mechanisms and Treatments.

Primary osteoporosis is closely linked to hormone deficiency, which disrupts the balance of bone remodeling. It affects postmenopausal women but also significantly impacts older men. Estrogen can promote the production of osteoprotegerin, a decoy receptor for RANKL, thereby preventing RANKL from activating osteoclasts. Furthermore, estrogen promotes osteoblast survival and function via activation of the Wnt signaling pathway. Likewise, androgens play a critical role in bone metabolism, primarily through their conversion to estrogen in men. Estrogen deficiency accelerates bone resorption throug

Genes predisposing tunneled catheter thrombosis in hemodialysis patients.

BackgroundThis study aims to investigate the association of genes predisposing thrombophilia with tunneled catheter thrombosis in hemodialysis patients.MethodsBetween October 2018 and December 2020, we compared the frequencies of genetic polymorphisms causing thrombophilia, including prothrombin G20210A, factor V Leiden, methylene tetrahydrofolate reductase (MTHFR) C677T, MTHFR A1298C, plasminogen activator inhibitor (PAI), factor XIII V34L and clinical characteristics of 52 patients with a history of 2 tunneled2 tunneled catheter thrombosis occlusions within a year (Group 1; 24 males, 28 fema

Role of Long Non-Coding RNA X-Inactive-Specific Transcript (XIST) in Neuroinflammation and Myelination: Insights from Cerebral Organoids and Implications for Multiple Sclerosis.

Background/Objectives: X-inactive-specific transcript (XIST) is a factor that plays a role in neuroinflammation. This study investigated the role of XIST in neuronal development, neuroinflammation, myelination, and therapeutic responses within cerebral organoids in the context of Multiple Sclerosis (MS) pathogenesis. Methods: Human cerebral organoids with oligodendrocytes were produced from XIST-silenced H9 cells, and the mature organoids were subsequently treated with either FTY720 or DMF. Gene expression related to inflammation and myelination was subsequently analyzed via qRT-PCR. Immunoflu

Modern Treatment of Skeletal Metastases: Multidisciplinarity and the Concept of Oligometastasis in the Recent Literature.

Bone metastases are a major concern in cancer management since they significantly contribute to morbidity and mortality. Metastatic lesions, commonly arising from breast, prostate, lung, and kidney cancers, affect approximately 25% of cancer patients, leading to severe complications such as pain, fractures, and neurological deficits. This narrative review explores contemporary approaches to bone metastases, emphasizing a multidisciplinary strategy and the evolving concept of oligometastatic disease. Oligometastases, defined by limited metastatic spread (1-5 lesions), offer a potential window f

Spatiotemperal Dynamics of Osteoarthritis: Преобразование значений от стенда до Бедсайда.

Остеоартрит (OA) представляет собой многогранное дегенеративное совместное расстройство, вызванное различными факторами риска, такими, как возраст, механический стресс, воспаление и метаболическое воздействие. Эти элементы способствуют его разнообразным фенотипам и эндотипам, что подчеркивает имманентную сложность болезни. Участие нескольких тканей и их взаимодействие еще больше осложняет расследование ОА. Нынешние ограничения в области технологий пространственного фенотификации в сочетании со сложной сетью многофакторных взаимодействий препятствуют обнаружению надежных ранних диагностических

Revisiting Proteasome Inhibitors: Molecular Underpinnings of Their Development, Mechanisms of Resistance and Strategies to Overcome Anti-Cancer Drug Resistance.

Proteasome inhibitors have shown relevant clinical activity in several hematological malignancies, namely in multiple myeloma and mantle cell lymphoma, improving patient outcomes such as survival and quality of life, when compared with other therapies. However, initial response to the therapy is a challenge as most patients show an innate resistance to proteasome inhibitors, and those that respond to the therapy usually develop late relapses suggesting the development of acquired resistance. The mechanisms of resistance to proteasome inhibition are still controversial and scarce in the literat

Gene therapy of rare diseases as a milestone in medicine - overview of the field and report on initial experiences in Slovenia.

Gene therapy has transitioned from a long-awaited promise to a clinical reality, offering transformative treatments for rare congenital diseases and certain cancers, which have a significant impact on patients' lives. Current approaches focus on gene replacement therapy, either in vivo or ex vivo, mostly utilizing viral vectors to deliver therapeutic genes into target cells. However, refining these techniques is essential to overcome challenges and complications associated with gene therapy to ensure long-term safety and efficacy. Slovenia has witnessed significant advancements in this field s

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… However, in some cases, the cost is lower than the long-term treatment of the same patients with other drugs, such as enzyme replacement therapy or clotting factor treatment in haemophilia. …

Цифровой двойник для неврологических условий: систематический обзор сферы охвата.

Цифровая двойная технология стала многообещающим подходом к развитию точной медицины в сложных болезнях, особенно в неврологии. Цель этого аналитического обзора заключалась в том, чтобы систематически картировать текущую литературу о цифрового двойного применения в неврологических условиях с уделением особого внимания характеристикам исследований, подходам к моделированию, источникам данных и клиническому применению. Всесторонний поиск six базы данных с момента создания по февраль 2026 выявленные 36 - исследования, отвечающие критериям включения. Полученные результаты свидетельствуют о быстром

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… trial data for enzyme replacement therapy (ERT), mechanistic model parameters Clinical trial optimization/Drug efficacy comparison QSP digital twins performed in silico comparison of avalglucosidase alfa vs. standard of care in virtual IOPD patients. … The framework addresses challenges of sparse and noisy medical data in individual-level predictions. | Medium [ 46 ] | USA | To develop a QSP-based digital twin approach to supplement clinical trial data for enzyme replacement therapies in Pompe disease | Computational modeling/in silico clinical trial …

Reconciling uncertainty of costs and outcomes with the need for access to orphan medicinal products: a comparative study of managed entry agreements across seven European countries.

BackgroundNational payers across Europe have been increasingly looking into innovative reimbursement approaches - called managed entry agreements (MEAs) - to balance the need to provide rapid access to potentially beneficial orphan medicinal products (OMPs) with the requirements to circumscribe uncertainty, obtain best value for money or to ensure affordability. This study aimed to identify, describe and classify MEAs applied to OMPs by national payers and to analyse their practice in Europe.MethodsTo identify and describe MEAs, national health technology assessments and reimbursement decision

Pruritus in Systemic Diseases: A Review of Etiological Factors and New Treatment Modalities.

Pruritus is the most frequently described symptom in dermatology and can significantly impair the patient's quality of life. In 10-50% of adults with persistent pruritus, it can be an important dermatologic clue for the presence of a significant underlying systemic disease such as renal insufficiency, cholestasis, hematologic disorder, or malignancy (Etter and Myers, 2002; Zirwas and Seraly, 2001). This review describes the presence of pruritus in different systemic diseases. It is quite important to discover the cause of pruritus for providing relief for the patients experiencing substantial

ESCP Spring Workshop 2023: Advancing clinical pharmacy and care in diabetes and cardiovascular comorbidities-Antwerp, 20-21 April 2023.

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:: 8th Европейский конгресс фармацевтики: выдержки из выступлений

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