Sublingual Research Articles

Maternal methylmercury exposure changes the proteomic profile of the offspring's salivary glands: Prospects on translational toxicology.

BackgroundMethylmercury (MeHg) remains a public health issue since developing organisms are particularly vulnerable to this environmental contaminant. This study investigated the effect of maternal MeHg exposure on the modulation of proteomic profile of parotid (PA), submandibular (SM), and sublingual (SL) glands of offspring rats.Materials and methodsPregnant Wistar rats were daily exposed to 40 μg/kg MeHg during both gestational and lactation periods. The proteomic profiles of the major salivary glands of the offspring rats were analyzed through mass spectrometry.ResultsThe offspring rats exposed to MeHg showed significant alterations in the proteomic profiles of the PA, SM, and SL glands. Altered proteins were associated with cytoskeleton components, tissue morphogenesis, and response to stimulus and stress.ConclusionThis original study showed that maternal MeHg exposure significantly modulates the expression of proteins and induces alterations in the proteomic profiles of developing salivary glands.

DEVELOPMENT AND CHARACTERIZATION OF TACROLIMUS TABLET FORMULATIONS FOR SUBLINGUAL ADMINISTRATION

Objective: The study aimed to prepare and characterize inclusion complexes of tacrolimus with β-cyclodextrin to improve its solubility and to formulate them into sublingual fast disintegrating tablets with a view to bypass the first-pass metabolism. Methods: Tacrolimus: β-cyclodextrin inclusion complexes (1:1 and 1:2 molar proportions) were prepared using the kneading method. Their characterization was accomplished by determining the drug content, solubility, Attenuated Total Reflection-Infrared Spectroscopy (ATR-IR), Scanning Electron Microscopy (SEM), Differential Scanning Calorimetry (DSC), and powder X-Ray Diffraction analysis (pXRD). These were then formulated to fast disintegrating tablets and evaluated for precompression as well as post compressional characteristics. Results: SEM analysis showed the inclusion complexes as rough, non-porous, irregular surfaced aggregate particles. DSC and pXRD analyses confirm the crystallinity change and partial conversion to the amorphous form of the drug in the inclusion complexes. From the solubility studies, it was observed that both the inclusion complexes of 1:2 molar ratio (14.82±0.889 µg/ml) and 1:1 molar ratio (12.72±0.1004 µg/ml) improved the aqueous solubility to greater extents in comparison to that of the pure drug (3.05±0.121 µg/ml). All the tablet formulations showed good precompression and mechanical properties. The inclusion complex loaded tablets exhibited a superior drug release pattern when compared to tablets prepared with tacrolimus alone. The optimized formulation (TT3) showed an in vitro disintegration time of 34.33 s and a percent drug release of 97.87. Conclusion: The inclusion complex formulation combined with the sublingual route of administration can be expected to result in an improved bioavailability of tacrolimus by increasing its solubility and bypassing first-pass metabolism.

Plant Food Allergy Improvement after Grass Pollen Sublingual Immunotherapy: A Case Series.

Background: Cross-reactivity between pollens and plant food has been widely described. Pollen extract subcutaneous immunotherapy in patients with pollens and plant food allergy has been shown to improve tolerance not only to inhalant allergens but also to reduce symptoms in patients with various food allergies. Methods: We retrospectively report our experience with 15 female patients with a positive history for moderate, persistent allergic rhinitis due to grass pollen and oropharyngeal symptoms after ingestion of different plant food. These patients followed a five-grass pollen sublingual tablet immunotherapy for three years in a discontinuous pre-co-seasonal scheme. Results: All 15 patients treated with the 5-grass pollen sublingual tablet immunotherapy, taken once daily for 3 years on a 7-month course, showed improved ocular/nasal symptoms, with a reduction in the use of symptomatic drugs (e.g., nasal corticosteroids and H1 antihistamines). After the first seven-month course of immunotherapy, all patients declared a good tolerance to the intake of fruits and vegetables, and in particular, good tolerance to the offending foods. Conclusions: In conclusion, we have observed improvement of both respiratory and plant food allergies after sublingual immunotherapy (SLIT) with a five-grass pollen tablet.

Sublingual Immunization with Chimeric C1q/CD40 Ligand/HIV Virus-like Particles Induces Strong Mucosal Immune Responses against HIV.

Development of a vaccine that can elicit robust HIV specific antibody responses in the mucosal compartments is desired for effective prevention of HIV via sexual transmission. However, the current mucosal vaccines have either poor immunogenicity when administered orally or invite safety concerns when administered intranasally. Sublingual immunization has received more attention in recent years based on its efficiency in inducing systemic and mucosal immune responses in both mucosal and extra-mucosal tissues. To facilitate the transport of the immunogen across the sub-mucosal epithelial barrier, we found that CD91, the receptor of C1q, is prevalently expressed in the sublingual mucosal lining, and thus, a modified chimeric C1q surface conjugated CD40L/HIV VLP was generated. The ability of this chimeric C1q/CD40L/HIV VLP to bind, cross the epithelial layer, access and activate the sub-mucosal layer dendritic cells (DCs), and ultimately induce enhanced mucosal and systemic immune responses against HIV is evaluated in this study. We found that C1q/CD40L/HIV VLPs have enhanced binding, increased transport across the epithelial layer, and upregulate DC activation markers as compared to CD40L/HIV VLPs alone. Mice immunized with C1q/CD40L/HIV VLPs by sublingual administration showed higher levels of IgA salivary antibodies against both HIV Gag and Env than mice immunized with CD40L/HIV VLPs. Moreover, sublingual immunization with C1q/CD40L/HIV VLPs induced more Env- and Gag-specific IFN-γ producing T cells than the CD40L/HIV VLPs group. Interestingly, C1q/CD40L/HIV VLP immunization can also induce more mucosal homing T cells than that in CD40L/HIV VLP group. Our data suggest that incorporation of C1q to CD40L/HIV VLPs is a promising novel strategy and that the sublingual immunization can be a favorite immunization route for HIV mucosal vaccines.

Study of the efficacy of sublingual route administration of levothyroxine Na nablets vs oral route in cases with refractory primary hypothyroidism

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Efficacy of Sublingual Administration Misoprostol 600 mcg Versus 800 mcg for Induced Abortion in Women with Early Pregnancy Loss: A Randomized Controlled Trial

Objective: To compare the complete abortion rate, the induction-to-abortion time, and side effects between 600 mcg and 800 mcg misoprostol sublingually. Materials and Methods: Total, of 108 pregnant women with gestational age less than 12 weeks with early pregnancy loss from March 2020 to February 2021 at the Department of Obstetrics and Gynecology, Queen Savang Vadhana Memorial Hospital, were included. For group 1 (n=54), 600 mcg misoprostol was administrated sublingually. For group 2 (n=54), 800 mcg misoprostol was administrated sublingually. If the abortion did not occur, the repeated misoprostol in the same dose would be administrated sublingually every 6 hours for a maximum of three doses. Results: There was no significant difference in the complete abortion rate between the two groups (55.6% in the 600 mcg misoprostol group, 64.7% in the 800 mcg misoprostol group, p=0.339, and 95% CI 0.082 to 1.862). The induction-to-abortion time was 9.5 hours (IQR 6.75 to 48.00) in the 600 mcg misoprostol group and 10 hours (IQR 6.00 to 60.00) in the 800 mcg misoprostol group. The side effects of both groups were similar, included abdominal pain, diarrhea, nausea and vomiting, fever, heavy bleeding, and headache. Conclusion: The efficacy of the 600 mcg misoprostol was noninferior to 800 mcg misoprostol. The adverse effects were similar in both groups. Mean induction-to-abortion time was also similar in both groups. Keywords: Early pregnancy loss; Misoprostol; Medical abortion

The Cannabis Extraction Product as an Adjuvant Treatment in Tourette’s Syndrome: A Case Report

Tourette’s syndrome (TS) is a pediatric onset of neuropsychiatric disorder characterized by motor and vocal tics. First line medication is dopaminergic blocking agents. Yet, these drugs are not effective in all patients and sometimes the side effects are intolerance. Cannabis and its derivatives are to use as an adjuvant treatment. They are used to improve tics in TS patients who failed from the first line treatment. The aim of the present report was to describe the clinical course after using the Government Pharmaceutical Organization (GPO) medical cannabis extraction product as an adjuvant treatment in TS patient. Here, the researchers reported a case of a 26-year-old female patient who had TS. She had received sublingual medical cannabis product. The clinical course and disease severity were recorded before and during the administration of the medical cannabis extraction product using several standards severity score: The Yale Global Tic Severity Scale (YGTSS), Tourette’s Syndrome Severity Scale (TSSS), Turette’s Disorder Scale (TODS), and quality of life using a standardized measure of health-related quality of life developed by the Euro Quality of life group (EQ-5D-5L). The researchers’ observation showed that sublingual administration of medical cannabis extraction product [tetrahydrocannabinol (THC):cannabidiol (CBD) 1:1 and THC enriched] improved both motor and vocal tics without significant adverse effect that came out to be improving the patient’s quality of life as a whole. Keywords: Tourette’s Syndrome (TS); The Government Pharmaceutical Organization (GPO); Medical cannabis extraction product; Cannabidiol; Tetrahydrocannabinol

Peculiarities of current melatonin application — successful experience and new opportunities

The paper presents current information about the physiological functions and pharmacological properties of hormone melatonin. Consideration was given to the results of clinical trials, confirming melatonin efficacy in the treatment of insomnia of various etiology in patients of different age groups in comparison of other hypnotics, both as monotherapy and combined therapy of arterial hypertension with the purpose of regulation of circadian rhythms in case of desynchronosis (jet lug, shift work, syndromes sleep phase disturbances). An experience of exogenous melatonin application at coronavirus disease (COVID‑19) has been analyzed. The review is based on search results in the PubMed, Medline, Scopus databases for the period 1997–2021 for the keywords melatonin, therapeutic use, insomnia, hypertension, circadian rhythm disturbances, COVID‑19.
 Data showed that melatonin was an effective and safe medication that can be recommended in all cases of sleep disturbances and for patients of any age with or without concomitant pathology. It is well tolerated and goes well with other drugs. Melatonin efficacy and safety was registered at its simultaneous use with antihypertensive, hypoglycemic and anti‑inflammatory drugs in elderly and middle‑aged people with arterial hypertension. Owing to its anti‑inflammatory, immunoregulatory, antioxidant effects, melatonin diminishes the risk of infections, inflammation, and oxidative stress in case of disease development, it promotes health in people at risk, has a neuroprotective effect in patients with COVID‑19, can serve as an adjuvant to boost anti‑SARS‑CoV‑2 vaccines. As an antioxidant and anti‑inflammatory agent, melatonin counteracts acute lung injury/acute respiratory distress syndrome caused by viral and bacterial infections.
 Melatonin preparation Melafresh (Prime Health Ltd., Canada) proved to be an effective addition to the therapy of sleep disorders of various etiology, especially in cases of their onset due to inconsistent circadian rhythms, it prevents or attenuates desynchronosis of circadian rhythms, violation of daily sleep/wakefulness cycles, decreases the number of episodes of awakening at night, restores full sleep after psycho‑emotional overload and stress, and promotes easy awakening. One of Melafresh advantages is its drug form (sublingual tablets) as it increases its bioavailability and concentration in blood.

Effectiveness of Sublingual Immunotherapy in the Treatment of HDM-Induced Nasobronchial Allergies: A 3-Year Randomized Case-Control Study From Kashmir.

Allergen immunotherapy (AIT) is the only disease-modifying treatment for allergic disorders that induces immunological tolerance through administration of specific allergens. Studies on AIT for subcutaneous route are in abundance; however, the efficacy of AIT in tablet form through sublingual route has not been well elucidated. The present prospective, parallel-group, controlled study sought to compare the efficacy of sublingual immunotherapy (SLIT) tablets with pharmacotherapy (PT) in 332 house dust mite (HDM)-specific allergic asthma and/or rhinitis patients over a period of 3 years. Patients were followed up for a 6-month run-in period and then randomly stratified as those who would receive SLIT, SLIT in addition to PT (SLIT+PT), and PT alone. AIT was administered in the form of sublingual tablets. Symptom and medication scores were measured every 3 months. In vitro evaluation of serum total and HDM specific immunoglobulin E (HDM sIgE) levels was carried out every 3 months, whereas in vivo skin prick test was performed annually for 3 years. Our study demonstrated sustained clinical improvement, reduction in inhaled corticosteroid (ICS) dose and duration as well as prevention from development of neosensitization to other aero allergens in HDM-allergic asthmatics and/or rhinitis patients treated with 3 years SLIT. Despite a remarkable clinical improvement with AIT, we observed that SLIT did not significantly change the skin reactivity to HDM at 3 years and there was no significant change in the ratio of serum total and HDM sIgE. Given the immune and disease modifying effects of AIT in allergic diseases, the present study supports the notion of its sublingual mode being an effective long-term immunomodulator in HDM-sensitized nasobronchial allergies.

Pharmacology-based toxicity assessment of molsidomine and ATP-LONG combination with singular and repetitive injections under experimental conditions

Abstract. The aim of the work was to study toxic properties of the new combined drug which comprise nitrovasodilator molsidomine and adenosine- 5’-triphosphate in a form of coordination compound with histidine, magnesium, and potassium (ATP-LONG). The drug was examined for its acute and subacute toxicity on Balb/c mice and Wistar rats of reproductive age with peroral (p/o) and sublingual (s/l) administrations. It has been established that LD50 of the substance contains over 10000 mg/kg (p/o) and 5010 mg/kg (s/l), which corresponds to the category of Practically non-toxic substances. The repetitive administrations within a 28 day period of the conditionally therapeutic dose of 260 mg/hg (s/l) did not cause any negative impact on physiological, biochemical, histological values in male and female rats. In doses 1300 and 2080 mg/kg, which exceed conditionally therapeutic doses by 5 and 8 times, the combination was not changing clinical laboratory urine and blood values but induced histological changes such as dilation and plethora of capillaries along with edema of smooth muscle cells of the brain, myocardium, liver, spleen, kidneys, and adrenal glands in rats. Additionally, the particular dosages of the combined substance provoked irritation of the mucous membrane of the tongue. Detected effects of the drug do not carry any pathological character and can be viewed as a specific reaction of the organism to high doses of nitrovasodilator. However, the duration and reversibility of unwanted consequences of molsidomine overdose, particularly in its combined form, need further investigation. Keywords: combination of molsidomine and ATP-LONG, acute and subacute toxicity

Two-phase non-invasive multi-disease detection via sublingual region.

Non-invasive multi-disease detection is an active technology that detects human diseases automatically. By observing images of the human body, computers can make inferences on disease detection based on artificial intelligence and computer vision techniques. The sublingual vein, lying on the lower part of the human tongue, is a critical identifier in non-invasive multi-disease detection, reflecting health status. However, few studies have fully investigated non-invasive multi-disease detection via the sublingual vein using a quantitative method. In this paper, a two-phase sublingual-based disease detection framework for non-invasive multi-disease detection was proposed. In this framework, sublingual vein region segmentation was performed on each image in the first phase to achieve the region with the highest probability of covering the sublingual vein. In the second phase, features in this region were extracted, and multi-class classification was applied to these features to output a detection result. To better represent the characterisation of the obtained sublingual vein region, multi-feature representations were generated of the sublingual vein region (based on color, texture, shape, and latent representation). The effectiveness of sublingual-based multi-disease detection was quantitatively evaluated, and the proposed framework was based on 1103 sublingual vein images from patients in different health status categories. The best multi-feature representation was generated based on color, texture, and latent representation features with the highest accuracy of 98.05%.

68 High First Dose Buprenorphine to Accelerate Induction in Emergency Department Opioid Use Disorder Patients

Assess the implementation, feasibility and patient outcomes of an accelerated buprenorphine treatment pathway where a first dose of 16 mg sublingual (SL) or greater is administered to treatment seeking emergency department (ED) patients with opioid use disorder (OUD).

72 Orally Dissolving, Thin Film Dexmedetomidine (BXCL501) Demonstrates Significant Reduction in Agitation Across a Range of Agitation Severity in Patients With Schizophrenia and Bipolar Disorder

Patients with bipolar disorder and schizophrenia experience acute agitation episodes that may require urgent management to avoid escalation. BXCL501 is an investigational orally dissolving thin film of the highly selective alpha-2a adrenergic receptor agonist, dexmedetomidine, for sublingual or buccal administration. This secondary analysis of 2 Phase 3 studies of acute agitation in patients with schizophrenia or bipolar disorder evaluated efficacy by baseline agitation severity on both the PANSS-Excited Component (PEC) total and the 5 items making up the PEC (excitement, tension, hostility, uncooperativeness, poor impulse control). Data were from 2 Phase 3, randomized, placebo-controlled studies of adults with bipolar disorder or schizophrenia, with a total score of ³14 on the PEC and ³4 on at least 1 of the 5 PEC items. Patients were randomized to either BXCL501 180 mg, 120 mg, or placebo. The primary endpoint was change from baseline PEC total score at 2 hours. Moderate and severe agitation were defined as a PEC total score of 14 to 19 or >19, respectively. Calmness was rated on the Agitation and Calmness Evaluation Scale (ACES). Mean change in PEC total score from baseline to 2 hours postdose was significantly (P < .0001) greater for 180 mg (-10.4 & -10.4) and 120 mg (-8.4 & -9.0) doses of BXCL501 vs placebo (-4.7 & -4.9) for the schizophrenia & bipolar groups, respectively. Significant (P < .01) improvements from baseline to 2 hours in PEC total score were observed with BXCL501 vs placebo among subgroups with moderate or severe agitation. Significant (P < .0001) improvements from baseline in each of the 5 components of the PEC were observed with both doses of BXCL501 compared to placebo. These findings were consistent in both the schizophrenia and bipolar disorder groups. There were no severe or serious drug-related adverse events. Safety and tolerability results were comparable in both trials. In the schizophrenia study, the most common treatment emergent adverse events (TEAEs) were somnolence (22%; 86% mild, 14% moderate), dizziness (4.3%), oral hypoesthesia (4.3%), and orthostatic hypotension (4.0%) In the bipolar disorder study, the most common TEAEs were somnolence (21%; 59% mild, 41% moderate), dry mouth (5.6%), dizziness (5.6%), hypotension (5.6%), and orthostatic hypotension (4.4%). No participant was unarousable as measured by the ACES. All participants were able to self-administer the film. BXCL501, an investigational orally dissolving thin film formulation of dexmedetomidine, demonstrated consistent statistically significant improvement in PEC total score compared to placebo, regardless of baseline agitation severity in both schizophrenia and bipolar disorder groups. Statistically significant improvement in PEC total and all individual items (excitement, tension, hostility, uncooperativeness, poor impulse control) was observed with both doses in both groups. The most common TEAEs in both groups were somnolence, dizziness, and orthostatic hypotension. BXCL501 represents a potential approach for treating acute agitation in adults with schizophrenia and bipolar disorder.

A REVIEW ON FORMULATION AND EVALUATION OF SUBLINGUAL TABLETS USING SUBLIMATION TECHNIQUE

A REVIEW ON FORMULATION AND EVALUATION OF SUBLINGUAL TABLETS USING SUBLIMATION TECHNIQUE

Development and Optimization of Asenapine Sublingual Film Using QbD Approach.

Asenapine, an atypical antipsychotic agent, has been approved for the acute and maintenance treatment of schizophrenia and manic episodes of bipolar disorder. However, the extensive hepatic metabolism limits its oral bioavailability. Therefore, the objective of the current investigation was to develop sublingual film containing asenapine to enhance the therapeutic efficacy. Sublingual films containing asenapine were fabricated using polyethylene oxide and hydroxypropyl methylcellulose by solvent casting method. Design of experiment was used as a statistical tool to optimize the proportion of the film-forming polymers in order to establish the critical quality attributes of the drug formulation. The process was studied in detail by assessing risk of each step as well as parameters and material attributes to reduce the risk to a minimum. A control strategy was defined to ensure manufacture of films according to the target product profile by evaluation of intermediate quality attributes at the end of each process step. Results of optimized formulations showed rapid disintegration, adequate folding endurance, good percentage elongation, tensile strength, and viscosity. Besides, the results from the in vitro dissolution/ex vivo permeation studies showed rapid dissolution (100% in 6min) and higher asenapine permeation (~ 80% in 90min) through the sublingual epithelium. In vivo study indicates greater asenapine absorption (31.18 ± 5.01% of administered dose) within 5min and was comparable with marketed formulation. In summary, the designing plan to develop asenapine formulation was successfully achieved with desired characteristics of the delivery tool for sublingual administration.

The Newest Battlefield Opioid, Sublingual Sufentanil: A Proposal to Refine Opioid Usage in the U.S. Military

There is an ongoing opioid epidemic in the USA, and the U.S. military is not immune to the health threat. To combat the epidemic, the Department of Defense (DoD) and Department of Veterans' Affairs (DVA) issued new clinical practice guidelines and launched the Opioid Safety Initiative aimed at reducing opioid prescriptions. Furthermore, the DoD continually refined opioid protocols for acute pain on the battlefield, evolving from intramuscular morphine to intravenous morphine administration to oral transmucosal fentanyl citrate lollipops (Actiq) to finally sublingual sufentanil tablets (SSTs, Dsuvia). Interestingly, the newest introduction of SSTs into the military sparked great controversy, as there are concerns over the drug's potential for misuse. However, although the opioid crisis may understandably foster an aversion to new candidate opioids, the therapeutic benefits of effective opioids in acute trauma settings should not be overlooked. SSTs may offer an improved analgesic option to meet the battlefield's unmet needs with its non-invasive, sublingual delivery system and favorable pharmacologic properties that mitigate the risk for side effects, addiction, and adverse outcomes. Accordingly, this commentary aims to (1) review the evolution of opioid use on the battlefield and discuss the medical benefits and limitations of SSTs in acute trauma settings, (2) highlight the importance of chronic pain management post-deployment through evidence-based non-opioid modalities, and (3) explore avenues of future research. Ultimately, we propose that SSTs are an important improvement from existing battlefield opioids and that refining, not abandoning, opioid usage will be key to effectively managing pain in the military.

Assessment of epinephrine sublingual stability and permeability pathways to enhance its permeability for the treatment of anaphylaxis

Prompt epinephrine (Epi) injection using auto-injectors is the initial life-saving out-of-hospital treatment for anaphylaxis. However, patients and healthcare providers are eagerly awaiting a more convenient alternative dosage form that would overcome auto-injectors drawbacks.Previously, we extensively evaluated multiple alternative fast-disintegrating sublingual Epi tablet (FDSTs) formulations. However, the sublingual stability of Epi and effect of modifying the sublingual microenvironment pH on its stability and transport pathways were not yet fully investigated.Results depicted that Epi remained sufficiently stable at various pHs in human saliva and porcine sublingual tissue's extract. Epi permeability (EP) through excised porcine sublingual membrane was greatest at pH 8.0 (p < 0.05), 11-fold higher than the negative control (Epi at pH 6.8). Sodium carbonate (Na Carb) 0.75% was the most efficient buffer to modify Epi solution pH to 8.0. Both sodium dodecyl sulfate (SDS) 0.075% and palmitoyl-DL-carnitine chloride (PCC) 1.2% increased paracellular EP 10-fold and 3-fold, respectively; however, both demonstrated a delayed enhancement (>5 min). Meanwhile, Na Carb and SDS combination increased EP 23-fold without a delay.It is evident that pH-modifiers or their SDS combination showed promising potential to enhance Epi sublingual permeability and further reduce the required Epi dose using FDSTs as a feasible alternative to Epi auto-injectors.

Vascular Endothelial Function Assessed by Flow-Mediated Vasodilatation in Young Adults Born Very Preterm or With Extremely Low Birthweight: A Regional Cohort Study.

Background: Preterm birth and low birthweight have been associated with increased risk of cardiovascular disease in young adults. Endothelial dysfunction is established as an early marker for development of atherosclerotic cardiovascular disease. Previous studies of endothelial function in young adults born very preterm or with extremely low birthweight have, however, shown diverging results.Objective: We aimed to evaluate the risk of cardiovascular disease as measured by vascular endothelial function in young adults born very preterm (<29 weeks of gestation) or with extremely low birthweight (<1,000 g), compared with term-born controls.Methods: This study included 50 young adults born very preterm or with extremely low birthweight and 49 term-born controls born in Norway in the periods 1982–1985, 1991–1992, and 1999–2000 at mean age 28 (±6) years. The endothelial function was assessed by ultrasound measured flow-mediated dilatation (FMD) of the right brachial artery. The arterial diameter was measured at baseline, after release of 5 min of occlusion, and after sublingual administration of nitroglycerine. FMD was reported as absolute and percentage diameter change from baseline and relative to nitroglycerine-induced dilatation.Results: The participants were mainly normal weight non-smokers, without hypertension, diabetes, or established cardiovascular disease. The cases and controls had mean blood pressure 112/71 (SD 12/9) and 112/69 (SD 11/8) mmHg, body mass index 24.0 (SD 4.2) and 24.4 (SD 4.5) kg/m2, and HbA1c 32.7 (SD 2.5) and 33.0 (SD 2.6) mmol/mol, respectively. For both groups, 4 (8%) were smokers. Mean FMD for the adults born very preterm or with extremely low birthweight was 0.17 mm (95% CI 0.14, 0.21) vs. 0.24 mm (95% CI 0.20, 0.28) for the controls (p = 0.01), corresponding to a percentage increase of 5.4% (95% CI 4.2, 6.6) and 7.6% (95% CI 6.2, 8.9), respectively (p = 0.02). The FMD relative to maximal nitroglycerine-induced dilatation was 20% and 31%, respectively (p = 0.001).Conclusions: Young adults born very preterm or with extremely low birthweight have significantly lower FMD compared with the term-born controls suggesting an increased risk of cardiovascular disease.

Y-2 reduces oxidative stress and inflammation and improves neurological function of collagenase-induced intracerebral hemorrhage rats

Intracerebral hemorrhage (ICH) is a devastating disease, and there is currently no specific pharmacological treatment that can improve clinical outcomes. Y-2 sublingual tablets, each containing 30 mg edaravone and 6 mg (+)-borneol, is undergoing a phase III clinical trial for treatment of ischemic stroke in China. The purpose of the present study is to investigate the efficacy and potential mechanism of Y-2 in a rat model of collagenase IV injection induced ICH. Sublingual administration of Y-2 at the dose of 1, 3 and 6 mg/kg improved ICH-induced sensorimotor dysfunction, alleviated cell death and histopathological change, restored the hippocampal long-term potentiation (LTP), reduced brain edema and maintained blood-brain barrier (BBB) integrality in ICH rats. Further study demonstrated that Y-2 could reduce inflammatory response and oxidative stress by decreasing the levels of myeloperoxidase (MPO), ionized calcium-binding adaptor protein-1 (Iba-1), inflammatory cytokines and oxidative products, inhibit transcription factor nuclear factor-κB (NF-κB) activation, cyclooxygenase-2 (COX-2) and matrix metallopeptidase 9 (MMP-9) expression in brain tissue around in the core regions of hematoma. Importantly, the protective efficacy of Y-2 from ICH-induced injury was superior to edaravone. In conclusion, Y-2 sublingual tablets might be a promising therapeutic agent for the treatment of ICH.

Aллерген-специфическая иммунотерапия в лечении бронхиальной астмы у детей

В структуре аллергической патологии ведущее место занимает бронхиальная астма, которая, согласно последним данным Всемирной организации здравоохранения, диагностируется у 235–300 миллионов жителей планеты и относится к тем заболеваниям, которые существенно снижают качество жизни пациентов. У детей бронхиальная астма остается одним из самых распространенных заболеваний респираторной системы, которые ассоциируются с риском инвалидизации и смертности. На основании адаптации международных клинических рекомендаций, отечественного опыта рабочая группа ежегодно обновляет подходы к лечению бронхиальной астмы у детей. В настоящее время доказано, что фармакотерапия астмы может эффективно контролировать ее симптомы и влиять на воспалительный процесс. Однако она не может влиять на специфический иммунный ответ и в случае прекращения приема лекарств симптомы болезни могут возвращаться. Единственным методом лечения, способным повлиять на естественный ход аллергии, является аллерген-специфическая иммунотерапия, которая позволяет уменьшить чувствительность организма ребенка к «виновному» аллергену и снизить активность хронического воспаления. Аллерген-специфическую иммунотерапию проводят с применением очищенных водно-солевых экстрактов аллергенов или выделенных из них отдельных аллергенных компонентов. Этот метод лечения обычно предусматривает подкожное или сублингвальное введение постепенно растущих количеств «виновных» аллергенов до достижения дозы, которая является эффективной в индукции иммунологической толерантности к аллергенам. Доказательная база эффективности применения аллерген-специ­фической иммунотерапии в лечении бронхиальной астмы в течение последних лет существенно расширилась. Полученные на сегодняшний день данные доказали, что проведение такого лечения позволяет изменить состав представительства цитокиновых маркеров, снизить чувствительность респираторного канала к экспозиции аллергена, предупредить расширение спектра причинно-значимых аллергенов, замедлить ход аллергического процесса, уменьшить потребность в лекарственных препаратах. Более того, сегодня можно утверждать, что по завершении успешных курсов аллерген-специфической иммунотерапии в течение длительного времени сохраняется ремиссия бронхиальной астмы. Таким образом, уникальное терапевтическое действие аллерген-специфической иммунотерапии диктует потребность ее широкого применения в лечении бронхиальной астмы у детей. Для поиска источников литературы изучались базы данных: Medline, Web of Science, the Cochrane Library, Scopus.