Potential Prophylactic Role Research Articles

Levocetrizine attenuates cyclophosphamide-induced lung injury through inhibition of TNF-α, IL-1β, TGF-β and MMP-9

Cyclophosphamide (CP) is an antineoplastic drug commonly used worldwide. Despite its spread, it causes fatal organ toxicity. Lung toxicity is a serious side effect of CP. Actually, in the past three years the world has been facing an un-predicted crisis following COVID-19 pandemic and the associated high-mortality rates attributed to respiratory distress. Accordingly; this study aimed to probe the potential prophylactic role of levocetrizine against CP-induced lung injury. Animals were allocated into three sets; control; CP and CP/Levo. CP was intraperitoneally injected in rats 150 mg/kg once on day 7. Levocetrizine was given orally for 14 days starting 7 days before CP injection. On the last day, all rats were sacrificed and lung tissues were kept for analysis. CP significantly elevated lung/body weight index, inflammatory cell counts, LDH, total protein, TNF-α, IL-1β, TGF-β and histamine levels in bronchoalveolar lavage (BAL). Moreover, it markedly increased expression of MMP-9 and contents of MDA, hydroxyproline, collagen and NOx besides decreasing GSH level and SOD activity in lung tissues. These biochemical results were further confirmed by histopathological examination. In contrast, treatment with levocetrizine significantly attenuated CP-induced pathological alterations. These findings propose that levocetrizine can attenuate CP-induced lung injury via exerting antioxidant, anti-inflammatory and anti-fibrotic effects.

Sustained Nrf2 Overexpression-Induced Metabolic Deregulation Can Be Attenuated by Modulating Insulin/Insulin-like Growth Factor Signaling.

The modulation of insulin/insulin-like growth factor signaling (IIS) is associated with altered nutritional and metabolic states. The Drosophila genome encodes eight insulin-like peptides, whose activity is regulated by a group of secreted factors, including Ecdysone-inducible gene L2 (ImpL2), which acts as a potent IIS inhibitor. We recently reported that cncC (cncC/Nrf2), the fly ortholog of Nrf2, is a positive transcriptional regulator of ImpL2, as part of a negative feedback loop aiming to suppress cncC/Nrf2 activity. This finding correlated with our observation that sustained cncC/Nrf2 overexpression/activation (cncCOE; a condition that signals organismal stress) deregulates IIS, causing hyperglycemia, the exhaustion of energy stores in flies' tissues, and accelerated aging. Here, we extend these studies in Drosophila by assaying the functional implication of ImpL2 in cncCOE-mediated metabolic deregulation. We found that ImpL2 knockdown (KD) in cncCOE flies partially reactivated IIS, attenuated hyperglycemia and restored tissue energetics. Moreover, ImpL2 KD largely suppressed cncCOE-mediated premature aging. In support, pharmacological treatment of cncCOE flies with Metformin, a first-line medication for type 2 diabetes, restored (dose-dependently) IIS functionality and extended cncCOE flies' longevity. These findings exemplify the effect of chronic stress in predisposition to diabetic phenotypes, indicating the potential prophylactic role of maintaining normal IIS functionality.

Hydroxychloroquine as Prophylaxis for COVID-19: A Review.

The impact of the COVID-19 pandemic worldwide has led to a desperate search for effective drugs and vaccines. There are still no approved agents for disease prophylaxis. We thus decided to use a drug repositioning strategy to perform a state-of-the-art review of a promising but controversial drug, hydroxychloroquine (HCQ), in an effort to provide an objective, scientific and methodologically correct overview of its potential prophylactic role. The advantage of using known drugs is that their toxicity profile is well known and there are fewer commercial interests (e.g., expired patents), thus allowing the scientific community to be freer of constraints. The main disadvantage is that the economic resources are almost always insufficient to promote large multinational clinical trials. In the present study, we reviewed the literature and available data on the prophylactic use of HCQ. We also took an in-depth look at all the published clinical data on the drug and examined ongoing clinical trials (CTs) from the most important CT repositories to identify a supporting rationale for HCQ prophylactic use. Our search revealed a substantial amount of preclinical data but a lack of clinical data, highlighting the need to further assess the translational impact of in vitro data in a clinical setting. We identified 77 CTs using a multiplicity of HCQ schedules, which clearly indicates that we are still far from reaching a standard of care. The majority of the CTs (92%) are randomized and 53% are being conducted in a phase 3 or 2/3 setting. The comparator is placebo or control in 55 (77%) of the randomized studies. Forty-eight (62%) CTs expect to enroll up to 1,000 subjects and 50 (71%) plan to recruit healthcare workers (HCW). With regard to drug schedules, 45 (58.5%) CTs have planned a loading dose, while 18 (23.4%) have not; the loading dose is 800 mg in 19 trials (42.2%), 400 mg in 19 (42.2%), 600 mg in 4 (8.9%) and 1,200 mg in 1 (2.2%). Forty trials include at least one daily schedule, while 19 have at least one weekly schedule. Forty-one (53.2%) will have a treatment duration of more than 30 days. Awaiting further developments that can only derive from the results of these prospective randomized CTs, the take-home message of our review is that a correct methodological approach is the key to understanding whether prophylactic HCQ can really represent an effective strategy in preventing COVID-19.

Potential prophylactic role of silicon against brown rust (Puccinia melanocephala) in sugarcane

Some benefits of silicon (Si) fertilization have been reported in sugarcane plants, but information about the effects of Si on brown rust (Puccinia melanocephala) remain scarce, even though this plant disease is widespread in several areas around the world. The objective of this study was to evaluate whether Si potentiates the production of antimicrobial metabolites in sugarcane plants in response to infection by P. melanocephala. Experiments with a sugarcane cultivar (SP70–1143) susceptible to brown rust were conducted in pots (3 L) under greenhouse conditions using a randomized complete block design with four treatments: with and without Si (equivalent to 0 and 800 kg ha−1 of Si, denominated -Si and + Si, respectively), sprayed with water or inoculated with a suspension of P. melanocephala urediniospores. Liquid potassium silicate was applied in soil as a source of Si. Si fertilization increased soil Si and Si concentration in plants, which correspondingly decreased brown rust severity and sporulation of P. melanocephala in leaves. Silicon fertilization increased the concentration of sucrose and cis-aconitic acid and reduced the concentration of chlorogenic acid (trans-3-caffeoylquinic acid) in sugarcane leaves inoculated with the pathogen. In vitro germination of P. melanocephala was reduced in contact with all metabolites isolated by UHPLC-DAD (chlorogenic acid and C-glycosylated flavones) from the sugarcane leaves. This work helps to elucidate the potential prophylactic role of Si in the interaction between P. melanocephala and sugarcane.

Protective effects of grape seed procyanidin on isoflurane-induced cognitive impairment in mice

Context Oxidative imbalance-induced cognitive impairment is among the most urgent clinical concerns. Isoflurane has been demonstrated to impair cognitive function via an increase in oxidative stress. GSP has strong antioxidant capacities, suggesting potential cognitive benefits. Objective This study investigates whether GSP pre-treatment can alleviate isoflurane-induced cognitive dysfunction in mice. Materials and methods C57BL/6J mice were pre-treated with either GSP 25–100 mg/kg/d for seven days or GSP 100–400 mg/kg as a single dose before the 6 h isoflurane anaesthesia. Cognitive functioning was examined using the fear conditioning tests. The levels of SOD, p-NR2B and p-CREB in the hippocampus were also analysed. Results Pre-treatment with either a dose of GSP 50 mg/kg/d for seven days or a single dose of GSP 200 mg/kg significantly increased the % freezing time in contextual tests on the 1st (72.18 ± 12.39% vs. 37.60 ± 8.93%; 78.27 ± 8.46% vs. 52.72 ± 2.64%), 3rd (93.80 ± 7.62% vs. 52.94 ± 14.10%; 87.65 ± 10.86% vs. 52.89 ± 1.73%) and 7th (91.36 ± 5.31% vs. 64.09 ± 14.46%; 93.78 ± 3.92% vs. 79.17 ± 1.79%) day after anaesthesia. In the hippocampus of mice exposed to isoflurane, GSP 200 mg/kg increased the total SOD activity on the 1st and 3rd day and reversed the decreased activity of the NR2B/CREB pathway. Discussion and conclusions These findings suggest that GSP improves isoflurane-induced cognitive dysfunction by protecting against perturbing antioxidant enzyme activities and NR2B/CREB pathway. Therefore, GSP may possess a potential prophylactic role in isoflurane-induced and other oxidative stress-related cognitive decline.

The potential role for berberine, an alkaloid dietary supplement, in mitigating the subclinical pathology and delaying onset of rheumatoid arthritis

Abstract Berberine (BBR), a dietary supplement, is primarily marketed for the alleviation of polycystic ovary syndrome, type II diabetes, and inflammatory bowel disorders, with evidence from successful clinical trials. However, evidence also suggests that BBR might alleviate symptoms of rheumatoid arthritis in vivo, and have a potential prophylactic role from in vitrostudies. We examined BBR’s prophylactic potential for delaying onset of collagen-induced arthritis (CIA) in DBA/1J mice. To induce arthritis, mice were injected with a collagen/CFA emulsion on day 0 and a booster injection of collagen/IFA on day 18. Mice were either treated with 1 mg/kg of BBR daily (CIA+BBR group) or a vehicle control (CIA+PBS) via IP injections from day 0 to day 28, were left untreated (CIA group), or were in a non-arthritic control group. Incidence of arthritis by day 28 in CIA+BBR mice was 40%, compared to 90% in the CIA and CIA+PBS groups. Populations of B cells and T cells from the spleens and draining lymph nodes were examined from random mice across treatment groups during the pre-clinical stage of arthritis (day 14), and from the remaining mice on day 28 when arthritic signs and symptoms were expected to be apparent. Expression of co-stimulatory molecules CD80, CD86, MHC Class II, and CD40 was quantified on CD19+ B cells, and CD40L and CD28 on CD4+/CD3+ T cells. The concentrations of collagen type II-specific IgG2a, IgG1, and total IgG was obtained via ELISA. Finally, leukocyte infiltration into synovial tissue was imaged via confocal microscopy and compared across treatment groups on day 14 and day 28. The results indicate that there may be a potential role for BBR as a prophylactic supplement, although further examination into mechanism of action must be elucidated.

Bone Trough Lateral Meniscal Allograft Transplantation: The Tapered Teardrop Technique

The meniscus plays a vital role in knee biomechanics, and its physical absence or functional incompetence (e.g., irreparable root or radial tear) leads to unacceptably high rates of joint degeneration in affected populations. Meniscal allograft transplantation has been used successfully to treat patients with postmeniscectomy syndrome, and there is early laboratory and radiographic evidence hinting at a potential prophylactic role in preventing joint degeneration. We present a technique for lateral meniscal allograft transplantation using the CONMED Meniscal Allograft Transplantation system.

Protective effect of tadalafil in diabetic nephropathy induced rat model

Background: Among various mechanisms involved in the pathogenesis of diabetic nephropathy (DN), abnormalities in renal nitric oxide (NO) generation has attracted a lot of attention. Tadalafil, a competitive inhibitor of cyclic guanosine monophosphate (cGMP)-specific phosphodiesterase type 5 commonly used in the treatment of erectile dysfunction was suggested to play a potential prophylactic role for DN. However, this role has not been fully elucidated. The present study was designed to explore the potential beneficial effect of low- dose tadalafil on the progression of diabetic nephropathy in streptozotocin (STZ) induced diabetic rat model.Methods: After injection of STZ and verifying establishment of diabetes, rats were divided into 4 groups: control, diabetic-control, tadalafil-treated non-diabetic, and tadalafil-treated diabetic groups. Biochemical and hemodynamic parameters affecting the renal function such as blood glucose level, serum level of urea and creatinine, renal blood flow, urine volume, urinary albumin excretion, Na+ and K+ excretion, renal level of nitrite and nitrate, plus renal tissues antioxidant parameters (total antioxidant capacity, superoxide dismutase activity and glutathione content) were detected 8 weeks after administration of tadalafil. Histopathological and electron microscopy examination were performed.Results: Our results demonstrated that tadalafil attenuated the glycemic, renal biochemical, microscopic and ultramicroscopic changes/injuries caused by STZ- induced diabetes. Tadalafil could effectively increase renal blood flow and ameliorate glomerular basement membrane thickening.Conclusions: From the results it can be concluded that tadalafil protects rats against streptozotocin-induced DN possibly, in part, through its effect on renal nitric oxide level and its antioxidant activity.

Mannitol – Potential Prophylactic Role in Hemodialysis Initiation

Mannitol – Potential Prophylactic Role in Hemodialysis Initiation

Potential prophylactic role of aminoguanidine in diabetic retinopathy and nephropathy in experimental animals

This study sought to determine the potential prophylactic and antioxidant effects of aminoguanidine in experimentally induced diabetes. Four groups of Wistar rats, each composed of ten rats, were used. Two groups served as control. In group 3, diabetes was induced by a single intraperitoneal injection of streptozotocin (65 mg kg-1). In group 4, diabetes was induced and treated with aminoguanidine (100 mg kg-1 daily) orally for 3 months. Levels of serum glucose, glutathione peroxidase, glutathione reductase and erythrocytes catalase were analyzed on day 90 of the experiment. Retinal and kidney specimens were examined histopathologically after sacrifice of the animals. A significant antioxidant effect of aminoguanidine and its prophylactic role in diabetic retinopathy and nephropathy were observed in experimental animals.

Statins, bugs and prophylaxis: intriguing possibilities

Statin therapy may represent a potential prophylactic intervention in certain high-risk scenarios, for example in pandemic influenza and in those undergoing aggressive medical treatments. Emerging data indicate a potential prophylactic role in these high-risk groups.