scholarly journals Il trapianto di utero. Aspetti medici, bioetici e giuridici

2015 ◽  
Vol 64 (1) ◽  
Author(s):  
Maurizio Faggioni
Keyword(s):  
Clinical Trials ◽  
Ethical Issues ◽  
Standard Practice ◽  
Alternative Option ◽  
Uterine Transplantation

Le donne con infertilità da fattore uterino (FUI) dovuto a motivi congeniti (es. sindrome di Rokitansky) o a isterectomia non hanno alcuna possibilità di realizzare il loro desiderio di maternità se non ricorrendo all’adozione o alla maternità surrogata che, però, è proibita in molti paesi. Il trapianto di utero, attualmente in studio, potrebbe rappresentare una alternativa per le donne che desiderano fare esperienza della gravidanza. Dopo decenni di ricerche animali, in Svezia si è avuto la prima nascita dopo trapianto di utero e fecondazione in vitro e questo prova che il trapianto di utero potrebbe essere un trattamento per la FUI. In linea di principio il trapianto è accettabile, ma ci sono molti problemi etici che devono essere considerati nel contesto della sperimentazione e di una eventuale introduzione nella pratica clinica. ---------- Women with uterine factor infertility (UFI) stemming from congenital causes (e.g. Rokitansky syndrome) or from hysterectomy are not able to fulfill their longing for motherhood except resorting to adoption or surrogacy, a practice that is forbidden in many countries. The uterine transplantation is currently under study as an alternative option for women who desire experience pregnancy. After decades of animal researches, in Sweden the first livebirth after uterine transplantation and IVF has been reported and this report is a proof for uterine transplantation as a treatment for UFI. Uterine transplantation is, as principle, morally acceptable, but many ethical issues must be considered in the context of clinical trials and eventually of standard practice.

Traditional Medicines, HIV, and Related Infections

2011 ◽  
Vol 23 (1) ◽  
pp. 159-164 ◽  
Author(s):  
M. Patel ◽  
P. Bessong ◽  
H. Liu
Keyword(s):  
Clinical Trials ◽  
Immune System ◽  
Ethical Issues ◽  
Mechanisms Of Action ◽  
Antiretroviral Drugs ◽  
In Vivo Studies ◽  
Traditional Medicines ◽  
Anti Hiv

Traditional medicines are an integral part of health care worldwide, even though their efficacy has not been scientifically proven. HIV-infected individuals may use them singularly or in combination with conventional medicines. Many in vitro studies have proven the anti-HIV, anti- Candida, and anti–herpes simplex virus potential of traditional plants and identified some of the mechanisms of action. Very few in vivo studies are available that involve a small number of participants and show controversial results. In addition, knowledge is limited of the role of traditional medicines in the enhancement of the immune system. The use of traditional medicines with antiretroviral drugs (ARVs) has created a problem because drug interactions compromise the efficacy of ARVs. Several currently popular plants have been studied in the laboratory for their interaction with ARVs, with disadvantageous results. Unfortunately, no clinical trials are available. The science of traditional medicines is relatively new and is at present being modernized worldwide. However, there are still ethical issues regarding traditional medicines that need to be addressed—for example, regulations regarding quality control and standardization of medicines, regulation and education of healers who deliver these medicines, and unregulated clinical trials. The workshop addressed the following questions about traditional medicine and their use in HIV infection: What are the mechanisms of action of anti-HIV traditional medicines? Should traditional medicines be used in conjunction with ARV? Do traditional medicines enhance the immune system? Should medicinal plants be used for the control of oral infections associated with HIV? What are the ethical issues surrounding the use of traditional medicines for the treatment of HIV and associated infections?

scholarly journals Off label, compassionate and irrational use of medicines in Covid-19 pandemic, health consequences and ethical issues

2020 ◽  
Vol 25 (9) ◽  
pp. 3413-3419
Author(s):  
Francisco José Roma Paumgartten ◽  
Ana Cecilia Amado Xavier de Oliveira
Keyword(s):  
Clinical Trials ◽  
Ethical Issues ◽  
Convincing Evidence ◽  
In Vitro Assays ◽  
Off Label ◽  
Viral Respiratory Infection ◽  
Life Threatening ◽  
Antiparasitic Drugs ◽  
Heart Disorders

Abstract When Covid-19 emerged in December last year, there was no vaccine nor was there specific effective treatment for this fast-spreading and life-threatening viral respiratory infection. Clinical trials were planned and are in progress to investigate whether drugs used for influenza, HIV and other viruses, and also anthelmintics (ivermectin, nitazoxanide, niclosamide), and antimalarials (chloroquine, hydroxychloroquine) showing antiviral activity in in vitro assays, are effective and safe for Covid-19. So far there is no convincing evidence that these antiviral and antiparasitic drugs are of any benefit for Covid-19. Notwithsanding the absence of evidence of clinical efficacy, these drugs are widely used outside of clinical trials (off label) for prophylaxis and treatment of this viral infection. The rationale behind the prescription of macrolide antibiotics (azithromycin) for Covid-19 is obscure as well. The widespread prescription and use of drugs of unproven efficacy and safety for Covid-19 is at odds with the rational use of medicines, a cornerstone principle of pharmacotherapy advanced by WHO in 1985. This irrational use of drugs is cause for concern because some of them are associated with serious heart disorders and deaths.

Modulation of Matrix Metalloproteinases by Plant-Derived Products

2020 ◽  
Vol 20 ◽  
Author(s):  
Nur Najmi Mohamad Anuar ◽  
Nurul Iman Natasya Zulkafali ◽  
Azizah Ugusman
Keyword(s):  
Clinical Trials ◽  
Natural Products ◽  
Matrix Metalloproteinases ◽  
Animal Studies ◽  
Current Knowledge ◽  
In Vitro Models ◽  
In Vivo Studies ◽  
Extracellular Matrix Components

: Matrix metalloproteinases (MMPs) are a group of zinc-dependent metallo-endopeptidase that are responsible towards the degradation, repair and remodelling of extracellular matrix components. MMPs play an important role in maintaining a normal physiological function and preventing diseases such as cancer and cardiovascular diseases. Natural products derived from plants have been used as traditional medicine for centuries. Its active compounds, such as catechin, resveratrol and quercetin, are suggested to play an important role as MMPs inhibitors, thereby opening new insights into their applications in many fields, such as pharmaceutical, cosmetic and food industries. This review summarises the current knowledge on plant-derived natural products with MMP-modulating activities. Most of the reviewed plant-derived products exhibit an inhibitory activity on MMPs. Amongst MMPs, MMP-2 and MMP-9 are the most studied. The expression of MMPs is inhibited through respective signalling pathways, such as MAPK, NF-κB and PI3 kinase pathways, which contribute to the reduction in cancer cell behaviours, such as proliferation and migration. Most studies have employed in vitro models, but a limited number of animal studies and clinical trials have been conducted. Even though plant-derived products show promising results in modulating MMPs, more in vivo studies and clinical trials are needed to support their therapeutic applications in the future.

scholarly journals Targeting RON receptor tyrosine kinase for treatment of advanced solid cancers: antibody–drug conjugates as lead drug candidates for clinical trials

2020 ◽  
Vol 12 ◽  
pp. 175883592092006
Author(s):  
Hang-Ping Yao ◽  
Sreedhar Reddy Suthe ◽  
Xiang-Min Tong ◽  
Ming-Hai Wang
Keyword(s):  
Clinical Trials ◽  
Tyrosine Kinase ◽  
Receptor Tyrosine Kinase ◽  
Targeted Therapeutics ◽  
Antibody Drug Conjugates ◽  
Drug Candidates ◽  
Drug Conjugates ◽  
Ron Receptor ◽  
Antibody Drug

The recepteur d’origine nantais (RON) receptor tyrosine kinase, belonging to the mesenchymal-to-epithelial transition proto-oncogene family, has been implicated in the pathogenesis of cancers derived from the colon, lung, breast, and pancreas. These findings lay the foundation for targeting RON for cancer treatment. However, development of RON-targeted therapeutics has not gained sufficient attention for the last decade. Although therapeutic monoclonal antibodies (TMABs) targeting RON have been validated in preclinical studies, results from clinical trials have met with limited success. This outcome diminishes pharmaceutical enthusiasm for further development of RON-targeted therapeutics. Recently, antibody–drug conjugates (ADCs) targeting RON have drawn special attention owing to their increased therapeutic activity. The rationale for developing anti-RON ADCs is based on the observation that cancer cells are not sufficiently addicted to RON signaling for survival. Thus, TMAB-mediated inhibition of RON signaling is ineffective for clinical application. In contrast, anti-RON ADCs combine a target-specific antibody with potent cytotoxins for cancer cell killing. This approach not only overcomes the shortcomings in TMAB-targeted therapies but also holds the promise for advancing anti-RON ADCs into clinical trials. In this review, we discuss the latest advancements in the development of anti-RON ADCs for targeted cancer therapy including drug conjugation profile, pharmacokinetic properties, cytotoxic effect in vitro, efficacy in tumor models, and toxicological activities in primates.

scholarly journals 1592. Antimicrobial Activity of Ceftazidime-Avibactam and Comparator Agents Against Enterobacterales and Pseudomonas aeruginosa With Overexpression of AmpC β-Lactamase From Phase 3 Clinical Trials

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S792-S793
Author(s):  
Lynn-Yao Lin ◽  
Dmitri Debabov ◽  
William Chang ◽  
Urania Rappo
Keyword(s):  
Clinical Trials ◽  
Active Agent ◽  
Complicated Urinary Tract Infection ◽  
Carbapenem Resistance ◽  
Vitro Activity ◽  
In Vitro Activity ◽  
Control Groups ◽  
In Vitro Susceptibility ◽  
Intra Abdominal Infection

Abstract Background AmpC overproduction is a main mechanism of carbapenem resistance, in the absence of acquired carbapenemases. Ceftazidime-avibactam (CAZ-AVI) has potent in vitro activity against AmpC-producing P. aeruginosa and Enterobacterales that are resistant to carbapenems and other β-lactams. Methods Activity of CAZ-AVI and comparators was evaluated against AmpC-overproducing Enterobacterales (n=77) and P. aeruginosa (n=53) collected from 4 CAZ-AVI clinical trials: RECLAIM (complicated intra-abdominal infection [cIAI]), REPRISE (cIAI/complicated urinary tract infection [cUTI]), RECAPTURE (cUTI) and REPROVE (hospital-acquired pneumonia/ventilator associated pneumonia). In vitro susceptibility of CAZ-AVI and comparators was performed by broth microdilution using ThermoFisher custom panels. CLSI breakpoints were used to determine susceptibility. Quantitative PCR and microarray data were used to characterize presence and expression of AmpC. Clinical response at test of cure was assessed. Results Against 77 AmpC-overproducing Enterobacterales isolates, meropenem-vaborbactam (MVB) (98.7% susceptible [S]), CAZ-AVI (96.1% S), and meropenem (MEM) (96.1% S) had similar in vitro activity (Table), with greater in vitro activity than amikacin (AMK) (84.4% S), gentamicin (61.0% S), and ceftolozane-tazobactam (TZC) (35.1% S). Clinical cures in patients with baseline AmpC-overproducing Enterobacterales were 21/26 (81%) in CAZ-AVI group vs 17/20 (85%) in control groups. Against 53 AmpC-overproducing P. aeruginosa isolates, CAZ-AVI (73.6% S) showed greater in vitro activity than AMK (69.8% S), TZC (58.5% S), and MEM (37.7% S). Clinical cures in patients with baseline AmpC-overproducing P. aeruginosa were 12/14 (86%) in CAZ-AVI group vs 9/12 (75%) in control groups. MIC distributions against the same P aeruginosa isolates were CAZ-AVI (MIC50/90, 4/ >64 µg/mL), MVB (MIC50/90, 8/32 µg/mL), and MEM (MIC50/90, 8/32 µg/mL). Table Conclusion CAZ-AVI was the most active agent against AmpC-overproducing P. aeruginosa with higher proportion of clinical cure than controls. CAZ-AVI was also among the most active agents against AmpC-overproducing Enterobacterales, with >96% isolates susceptible. Disclosures Lynn-Yao Lin, MS, AbbVie (Employee) Dmitri Debabov, PhD, AbbVie (Employee) William Chang, BS, AbbVie (Employee) Urania Rappo, MD, MS, PharmD, Allergan (before its acquisition by AbbVie) (Employee)

scholarly journals Salvadora persica: Nature’s Gift for Periodontal Health

Antioxidants ◽  
2021 ◽  
Vol 10 (5) ◽  
pp. 712
Author(s):  
Mohamed Mekhemar ◽  
Mathias Geib ◽  
Manoj Kumar ◽  
Radha ◽  
Yasmine Hassan ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Periodontal Therapy ◽  
Periodontal Treatment ◽  
Oral Disease ◽  
Salvadora Persica ◽  
Periodontal Health ◽  
Clinical Investigations ◽  
Therapeutic Mechanisms ◽  
Pharmacologic Actions

Salvadora persica (SP) extract, displays very valuable biotherapeutic capacities such as antimicrobial, antioxidant, antiparasitic and anti-inflammatory effects. Numerous investigations have studied the pharmacologic actions of SP in oral disease therapies but its promising outcomes in periodontal health and treatment are not yet entirely described. The current study has been planned to analyze the reported effects of SP as a support to periodontal therapy to indorse regeneration and healing. In consort with clinical trials, in vitro investigations show the advantageous outcomes of SP adjunctive to periodontal treatment. Yet, comprehensive supplementary preclinical and clinical investigations at molecular and cellular levels are indispensable to reveal the exact therapeutic mechanisms of SP and its elements for periodontal health and therapy.

scholarly journals Recent Impact of Microfluidics on Skin Models for Perspiration Simulation

Membranes ◽  
2021 ◽  
Vol 11 (2) ◽  
pp. 150
Author(s):  
Genís Rabost-Garcia ◽  
Josep Farré-Lladós ◽  
Jasmina Casals-Terré
Keyword(s):  
Sweat Gland ◽  
Ethical Issues ◽  
Wearable Sensors ◽  
Surface Characteristics ◽  
Skin Surface ◽  
Wearable Technology ◽  
Alternative Strategies ◽  
Accurate Model ◽  
Key Features

Skin models offer an in vitro alternative to human trials without their high costs, variability, and ethical issues. Perspiration models, in particular, have gained relevance lately due to the rise of sweat analysis and wearable technology. The predominant approach to replicate the key features of perspiration (sweat gland dimensions, sweat rates, and skin surface characteristics) is to use laser-machined membranes. Although they work effectively, they present some limitations at the time of replicating sweat gland dimensions. Alternative strategies in terms of fabrication and materials have also showed similar challenges. Additional research is necessary to implement a standardized, simple, and accurate model representing sweating for wearable sensors testing.

scholarly journals Melatonin in Cancer Treatment: Current Knowledge and Future Opportunities

Molecules ◽  
2021 ◽  
Vol 26 (9) ◽  
pp. 2506
Author(s):  
Wamidh H. Talib ◽  
Ahmad Riyad Alsayed ◽  
Alaa Abuawad ◽  
Safa Daoud ◽  
Asma Ismail Mahmod
Keyword(s):  
Clinical Trials ◽  
Current Knowledge ◽  
Biological Activities ◽  
Experimental Studies ◽  
Therapeutic Effects ◽  
Cell Proliferation Inhibition ◽  
Different Types ◽  
Solid Foundation

Melatonin is a pleotropic molecule with numerous biological activities. Epidemiological and experimental studies have documented that melatonin could inhibit different types of cancer in vitro and in vivo. Results showed the involvement of melatonin in different anticancer mechanisms including apoptosis induction, cell proliferation inhibition, reduction in tumor growth and metastases, reduction in the side effects associated with chemotherapy and radiotherapy, decreasing drug resistance in cancer therapy, and augmentation of the therapeutic effects of conventional anticancer therapies. Clinical trials revealed that melatonin is an effective adjuvant drug to all conventional therapies. This review summarized melatonin biosynthesis, availability from natural sources, metabolism, bioavailability, anticancer mechanisms of melatonin, its use in clinical trials, and pharmaceutical formulation. Studies discussed in this review will provide a solid foundation for researchers and physicians to design and develop new therapies to treat and prevent cancer using melatonin.

Counterpoint: Chemosensitivity Assays for Recurrent Ovarian Cancer

2011 ◽  
Vol 9 (1) ◽  
pp. 121-124 ◽  
Author(s):  
Maurie Markman
Keyword(s):  
Ovarian Cancer ◽  
Clinical Trials ◽  
Recurrent Ovarian Cancer ◽  
Evidence Based ◽  
Chemosensitivity Assay ◽  
Reliable Evidence ◽  
In Vitro Chemosensitivity ◽  
Frequent Use ◽  
Chemosensitivity Assays

Unfortunately, no reliable evidence-based data have shown any in vitro chemosensitivity assay strategy to be clinically useful in the management of recurrent ovarian cancer, despite frequent use. Several clinical trials have been proposed with the potential to support or refute the relevance of these approaches.

scholarly journals Loss of Phosphatase and Tensin Homolog or Phosphoinositol-3 Kinase Activation and Response to Trastuzumab or Lapatinib in Human Epidermal Growth Factor Receptor 2–Overexpressing Locally Advanced Breast Cancers

2011 ◽  
Vol 29 (2) ◽  
pp. 166-173 ◽  
Author(s):  
Bhuvanesh Dave ◽  
Ilenia Migliaccio ◽  
M. Carolina Gutierrez ◽  
Meng-Fen Wu ◽  
Gary C. Chamness ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Epidermal Growth Factor Receptor ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Single Agent ◽  
Growth Factor Receptor ◽  
Breast Cancers ◽  
Trastuzumab Resistance ◽  
Epidermal Growth

Purpose Phosphatase and tensin homolog (PTEN) loss or activating mutations of phosphoinositol-3 (PI3) kinase (PIK3CA) may be associated with trastuzumab resistance. Trastuzumab, the humanized human epidermal growth factor receptor 2 (HER2) monoclonal antibody, and lapatinib, an epidermal growth factor receptor/HER2 tyrosine kinase inhibitor, are both established treatments for HER2-overexpressing breast cancers. Understanding of the cellular response to HER2-targeted therapies is needed to tailor treatments and to identify patients less likely to benefit. Methods We evaluated the effect of trastuzumab or lapatinib in three HER2-overexpressing cell lines. We confirmed the in vitro observations in two neoadjuvant clinical trials in patients with HER2 overexpression; 35 patients received trastuzumab as a single agent for the first 3 weeks, then docetaxel every 3 weeks for 12 weeks (trastuzumab regimen), whereas 49 patients received lapatinib as a single agent for 6 weeks, followed by trastuzumab/docetaxel for 12 weeks before primary surgery (lapatinib regimen). Apoptosis, Ki67, p-MAPK, p-AKT, and PTEN were assessed by immunohistochemistry. Genomic DNA was sequenced for PIK3CA mutations. Results Under low PTEN conditions, in vitro data indicate that lapatinib alone and in combination with trastuzumab was effective in decreasing p-MAPK and p-AKT levels, whereas trastuzumab was ineffective. In the clinical trials, we confirmed that low PTEN or activating mutation in PIK3CA conferred resistance to the trastuzumab regimen (P = .015), whereas low PTEN tumors were associated with a high pathologic complete response rate (P = .007). Conclusion Activation of PI3 kinase pathway is associated with trastuzumab resistance, whereas low PTEN predicted for response to lapatinib. These observations support clinical trials with the combination of both agents.

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