scholarly journals Pharmacological Activities of Sulfated Fucose-Rich Polysaccharides after Oral Administration: Perspectives for the Development of New Carbohydrate-Based Drugs

Marine Drugs ◽  
2021 ◽  
Vol 19 (8) ◽  
pp. 425
Author(s):  
Roberto J. C. Fonseca ◽  
Paulo A. S. Mourão
Keyword(s):  
Oral Administration ◽  
Oral Route ◽  
Experimental Models ◽  
Marine Organisms ◽  
New Drugs ◽  
Sulfated Polysaccharides ◽  
Pharmacological Effects ◽  
Sulfated Fucan ◽  
Hemostatic Effects

Marine organisms are a source of active biomolecules with immense therapeutic and nutraceutical potential. Sulfated fucose-rich polysaccharides are present in large quantities in these organisms with important pharmacological effects in several biological systems. These polysaccharides include sulfated fucan (as fucoidan) and fucosylated chondroitin sulfate. The development of these polysaccharides as new drugs involves several important steps, among them, demonstration of the effectiveness of these compounds after oral administration. The oral route is the more practical, comfortable and preferred by patients for long-term treatments. In the past 20 years, reports of various pharmacological effects of these polysaccharides orally administered in several animal experimental models and some trials in humans have sparked the possibility for the development of drugs based on sulfated polysaccharides and/or the use of these marine organisms as functional food. This review focuses on the main pharmacological effects of sulfated fucose-rich polysaccharides, with an emphasis on the antidislipidemic, immunomodulatory, antitumor, hypoglycemic and hemostatic effects.

scholarly journals Subacute Testicular Toxicity to Cadmium Exposure Intraperitoneally and Orally

2019 ◽  
Vol 2019 ◽  
pp. 1-14 ◽  
Author(s):  
Viviane G. S. Mouro ◽  
Ana L. P. Martins ◽  
Janaina Silva ◽  
Tatiana P. Menezes ◽  
Marcos L. M. Gomes ◽  
...  
Keyword(s):  
Oral Administration ◽  
Serum Testosterone ◽  
Oral Route ◽  
Experimental Models ◽  
Tubular Damage ◽  
Testicular Damage ◽  
Sod Activity ◽  
Administration Routes ◽  
Human Intoxication ◽  
Cd Exposure

The toxic effects of cadmium (Cd) on reproductive parameters are widely described in the literature. Experimental models often make use of the intraperitoneal route (i.p.), although human intoxication occurs preferentially by the oral route and can be continuous. However, little is known about the effect of Cd administration routes on the testicular structure. Thus, this study investigated the testicular impact of Cd exposure comparing both i.p. and oral routes, both single dose (SD), in addition to the oral route in fractional doses (FD). Swiss adult male mice received CdCl2 1.5 mg/kg i.p., 30 mg/kg oral SD, and 4.28 mg/kg oral FD for 7 consecutive days. The Cd bioaccumulation was observed in all routes, mainly in the oral FD route. The concentrations of testicular Ca and Cu decreased in all animals exposed to Cd, while Zn and Mn decreased only in the i.p. route. Testicular SOD activity was reduced in both routes of oral administration, while CAT increased in the i.p. route, and GST increased in all animals exposed to Cd. Changes in the tubular parameters and cell viability were observed in both routes of Cd administration but were more intense in the oral route, mainly in the FD. Serum testosterone concentration was reduced in both routes of oral administration. Tubular damage, such as the vacuolization of the seminiferous epithelium, germ cell detachment, and seminiferous tubule degeneration, occurred in all groups exposed to Cd. Therefore, the oral Cd administration presented greater potential to promote testicular damage, mainly when the metal was given in a fractionated way.

Antiplatelet Therapy in Acute Coronary Syndromes

2010 ◽  
Vol 6 (1) ◽  
pp. 58
Author(s):  
Sasha Koul ◽  
David Erlinge ◽  
◽  
Keyword(s):  
Platelet Function ◽  
Acute Coronary Syndromes ◽  
New Drugs ◽  
Antiplatelet Drugs ◽  
Bleeding Complications ◽  
Great Promise ◽  
Mortality Data ◽  
Poor Responders ◽  
Coronary Syndromes

Drugs inhibiting platelet function play a major role in the treatment of acute coronary syndromes (ACS). The first drug used, which is still considered the cornerstone of therapy today, is aspirin. Although very impressive in acutely decreasing rates of myocardial infarction as well as death, long-term data are scarce, despite our current recommendation for lifelong aspirin. The thienopyridines, most notably clopidogrel, are the next line of antiplatelet drugs. Well-documented data support the usage of clopidogrel for non-STEMI-ACS (NSTE-ACS). Although positive mortality data exist regarding clopidogrel and STEMI patients in a medically treated population, including thrombolysis, no larger amounts of randomised data exist in a primary PCI setting. Poor responders to aspirin and/or clopidogrel are a clinical problem, with these individuals constituting a higherrisk group for recurrent ischaemic events. Whereas very little can be done regarding aspirin resistance, clopidogrel resistance might be diminished by increasing the dosage or changing to more potent and newer-generation antiplatelet drugs. The role of glycoprotein IIb/IIIa inhibitors has diminished drastically and instead paved the way for thrombin antagonists (bivalirudin), which have fewer bleeding complications with resulting better long-term mortality. Novel adenosine diphosphate (ADP)-receptor blockers such as prasugrel and ticagrelor have shown increased efficacy over clopidogrel and hold great promise for the future. However, not all patients may benefit from these new drugs and economic constraints may also limit their use. Platelet function tests could possibly help in identifying risk groups in need of stronger platelet inhibition.

Antimicrobial peptides for the treatment of pulmonary tuberculosis, allies or foes?

2018 ◽  
Vol 24 (10) ◽  
pp. 1138-1147
Author(s):  
Bruno Rivas-Santiago ◽  
Flor Torres-Juarez
Keyword(s):  
Pulmonary Tuberculosis ◽  
Antimicrobial Peptides ◽  
Experimental Models ◽  
New Drugs ◽  
World Health ◽  
Public Health Issue ◽  
Health Organization ◽  
Drug Resistant Strains

Tuberculosis is an ancient disease that has become a serious public health issue in recent years, although increasing incidence has been controlled, deaths caused by Mycobacterium tuberculosis have been accentuated due to the emerging of multi-drug resistant strains and the comorbidity with diabetes mellitus and HIV. This situation is threatening the goals of World Health Organization (WHO) to eradicate tuberculosis in 2035. WHO has called for the creation of new drugs as an alternative for the treatment of pulmonary tuberculosis, among the plausible molecules that can be used are the Antimicrobial Peptides (AMPs). These peptides have demonstrated remarkable efficacy to kill mycobacteria in vitro and in vivo in experimental models, nevertheless, these peptides not only have antimicrobial activity but also have a wide variety of functions such as angiogenesis, wound healing, immunomodulation and other well-described roles into the human physiology. Therapeutic strategies for tuberculosis using AMPs must be well thought prior to their clinical use; evaluating comorbidities, family history and risk factors to other diseases, since the wide function of AMPs, they could lead to collateral undesirable effects.

Experimental Rodent Models of Vascular Dementia: A Systematic Review

2021 ◽  
Vol 19 ◽  
Author(s):  
Nidhi Tiwari ◽  
Jyoti Upadhyay ◽  
Mohd Nazam Ansari ◽  
Syed Shadab Raza ◽  
Wasim Ahmad ◽  
...  
Keyword(s):  
Vascular Dementia ◽  
Small Vessel Disease ◽  
Current Knowledge ◽  
Vascular Cognitive Impairment ◽  
Experimental Models ◽  
New Drugs ◽  
Amyloid Angiopathy ◽  
Vessel Disease ◽  
The Brain ◽  
Large Vessel Disease

: Vascular dementia (VaD) occurs due to cerebrovascular insufficiency, which leads to decreased blood circulation to the brain, thereby resulting in mental disabilities. The main causes of vascular cognitive impairment (VCI) are severe hypoperfusion, stroke, hypertension, large vessel disease (cortical), small vessel disease (subcortical VaD), strategic infarct, hemorrhage (microbleed), cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), and cerebral amyloid angiopathy (CAA),which leads to decreased cerebrovascular perfusion. Many metabolic disorders such as diabetes mellitus (DM), dyslipidemia, and hyperhomocysteinemia are also related to VaD. The rodent experimental models provide a better prospective for the investigation of the molecular mechanism of new drugs. A plethora of experimental models are available that mimic the pathological conditions and lead to VaD. This review article updates the current knowledge on the basis of VaD, risk factors, pathophysiology, mechanism, advantages, limitations, and the modification of various available rodent experimental models.

scholarly journals Sotalol does not interfere with the antielectroshock action of selected second-generation antiepileptic drugs in mice

2021 ◽  
Author(s):  
Kinga K. Borowicz-Reutt ◽  
Monika Banach ◽  
Monika Rudkowska ◽  
Anna Stachniuk
Keyword(s):  
Antiepileptic Drugs ◽  
Second Generation ◽  
Antidepressant Drug ◽  
Experimental Models ◽  
Long Term Memory ◽  
Avoidance Task ◽  
Maximal Electroshock ◽  
Term Memory ◽  
The Brain

Abstract Background Due to blocking β-receptors, and potassium KCNH2 channels, sotalol may influence seizure phenomena. In the previous study, we have shown that sotalol potentiated the antielectroshock action of phenytoin and valproate in mice. Materials and methods As a continuation of previous experiments, we examined the effect of sotalol on the action of four chosen second-generation antiepileptic drugs (oxcarbazepine, lamotrigine, pregabalin, and topiramate) against the maximal electroshock in mice. Undesired effects were evaluated in the chimney test (motor impairment) and step-through passive-avoidance task (long-term memory deficits). Finally, brain concentrations of antiepileptics were determined by fluorescence polarization immunoassay, while those of sotalol by liquid chromatography–mass spectrometry. Results Sotalol at doses of up to 100 mg/kg did not affect the electroconvulsive threshold. Applied at doses of 80–100 mg/kg, sotalol did not affect the antielectroshock action of oxcarbazepine, lamotrigine, pregabalin, or topiramate. Sotalol alone and in combinations with antiepileptics impaired neither motor performance nor long-term memory. Finally, sotalol significantly decreased the brain concentrations of lamotrigine and increased those of oxcarbazepine and topiramate. Pharmacokinetic interactions, however, did not influence the final antielectroshock effects of above-mentioned drug combinations. On the other hand, the brain concentrations of sotalol were not changed by second-generation antiepileptics used in this study. Conclusion Sotalol did not reduce the antielectroshock action of four second-generation antiepileptic drugs examined in this study. Therefore, this antidepressant drug should not interfere with antiseizure effects of lamotrigine, oxcarbazepine, pregabalin, and topiramate in patients with epilepsy. To draw final conclusions, our preclinical data should still be confirmed in other experimental models and clinical conditions.

scholarly journals Marine Organisms for the Sustainable Management of Plant Parasitic Nematodes

Plants ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 369
Author(s):  
Pasqua Veronico ◽  
Maria Teresa Melillo
Keyword(s):  
Crop Production ◽  
Control Strategies ◽  
Marine Organisms ◽  
New Drugs ◽  
Effective Control ◽  
Parasitic Nematodes ◽  
Plant Parasitic Nematodes ◽  
Wide Range ◽  
Plant Growth Stimulants ◽  
Plant Parasitic

Plant parasitic nematodes are annually responsible for the loss of 10%–25% of worldwide crop production, most of which is attributable to root-knot nematodes (RKNs) that infest a wide range of agricultural crops throughout the world. Current nematode control tools are not enough to ensure the effective management of these parasites, mainly due to the severe restrictions imposed on the use of chemical pesticides. Therefore, it is important to discover new potential nematicidal sources that are suitable for the development of additional safe and effective control strategies. In the last few decades, there has been an explosion of information about the use of seaweeds as plant growth stimulants and potential nematicides. Novel bioactive compounds have been isolated from marine cyanobacteria and sponges in an effort to find their application outside marine ecosystems and in the discovery of new drugs. Their potential as antihelmintics could also be exploited to find applicability against plant parasitic nematodes. The present review focuses on the activity of marine organisms on RKNs and their potential application as safe nematicidal agents.

scholarly journals Efficacy and Safety of Long-Term Low-Dose Clarithromycin in Patients With Refractory Chronic Sinusitis After Endoscopic Sinus Surgery: A Prospective Clinical Trial

2021 ◽  
pp. 014556132110320
Author(s):  
Han Chen ◽  
Bing Zhou ◽  
Qian Huang ◽  
Cheng Li ◽  
Yubin Wu ◽  
...  
Keyword(s):  
Oral Administration ◽  
Nasal Cavity ◽  
Endoscopic Sinus Surgery ◽  
Low Dose ◽  
Continuous Treatment ◽  
Sinus Surgery ◽  
Efficacy And Safety ◽  
Endoscopic Findings ◽  
Before And After

Objective: To observe the efficacy and safety of postoperative long-term low-dose oral administration of clarithromycin in patients with refractory chronic rhinosinusitis (RCRS), to explore the characteristics of postoperative microbiota in the nasal cavity in patients with RCRS, and to compare the differences and changes in microbiota in the nasal cavity before and after medication. Methods: This was a prospective, self-controlled study. Eighteen patients with RCRS who had persistent symptoms after endoscopic sinus surgery and standard therapy with normal immunoglobulin E and eosinophil level were included. Low dose (250 mg, once daily) clarithromycin was orally administrated for 12 weeks. Symptom severity and endoscopic findings were evaluated before, after 4 weeks, and 12 weeks of treatment, and nasal cavity microbiota was analyzed simultaneously. Results: A total of 18 patients with RCRS were enrolled and 17 patients completed the study. Four weeks after oral administration of clarithromycin, significant improvement was observed in subjective symptoms including nasal congestion, rhinorrhea, postnasal drip, and general discomfort, as well as endoscopic findings including general surgical cavity condition, rhinedema, and rhinorrhea ( P < .05). After continuous treatment to the 12th week, symptoms showed significant improvement compared with baseline, and endoscopic score showed significant improvement compared with both baseline and 4 weeks after treatment. Analysis of middle nasal meatus flora revealed a significant decrease of Streptococcus pneumoniae after 12 weeks of clarithromycin treatment ( P < .05), while the richness, composition, and diversity were similar before and after treatment. Patients enrolled experienced no adverse drug reaction or allergic reaction, nor clinical significant liver function impairment observed. Conclusion: Postoperative low-dose long-term oral administration of clarithromycin in patients with RCRS can improve the clinical symptoms and facilitate the mucosal epithelialization, with good tolerance and safety. The efficacy of clarithromycin in patients with RCRS may be related to its regulatory effect on nasal cavity microbiota.

scholarly journals Tofacitinib: An Option for Acute Severe Ulcerative Colitis?

2021 ◽  
pp. 1-3
Author(s):  
Sara Santos ◽  
Verónica Gamelas ◽  
Rita Saraiva ◽  
Guilherme Simões ◽  
Joana Saiote ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Clinical Improvement ◽  
Rescue Therapy ◽  
New Drugs ◽  
Multiple Drug ◽  
Disease Course ◽  
Efficacy And Safety ◽  
Severe Ulcerative Colitis ◽  
Rapid Absorption

Tofacitinib has emerged as a new option for ulcerative colitis. Its rapid absorption, metabolism, and clinical improvement make it an interesting option for rescue therapy in acute severe ulcerative colitis (ASUC), a situation with limited therapeutic options in patients with a long-term disease course and multiple drug failure. The management of ASUC in this setting becomes challenging, underlying the need for new drugs and data on their efficacy and safety. We describe 2 cases of acute episodes in which tofacitinib was used as a rescue therapy.

Sign in / Sign up

Export Citation Format

Share Document