Dimetindene Maleate Research Articles

Spectrophotometric Determination of Domperidone Maleate, Carvedilol, Dimetindene Maleate and Cinnarizine in Pharmaceuticals by Ion Association Complex Formation with Erythrosine B Dye

Spectrophotometric Determination of Domperidone Maleate, Carvedilol, Dimetindene Maleate and Cinnarizine in Pharmaceuticals by Ion Association Complex Formation with Erythrosine B Dye

Topical bioequivalence: Experimental and regulatory considerations following formulation complexity

Documenting topical bioequivalence can be an extremely complex process, which is intrinsically dependent on the formulation technological features. According to EMA guideline, for simple formulations, BE may be demonstrated by documenting the qualitative (Q1), quantitative (Q2), microstructure (Q3) and performance (Q4) equivalence. Nevertheless, when addressing complex semisolids, equivalence regarding local availability should also be demonstrated. The purpose of this study is to pursue this strategy using two opposite scenarios: a simple dimetindene maleate 1 mg/g gel formulation and a diclofenac diethylammonium 23.2 mg/g emulgel, representing a complex formulation. For both formulations, Q1/Q2 test (TP) and reference products (RP) were used. Rheology, in vitro release (IVRT) and in vitro permeation methods (IVPT) were developed and validated for both products.For the dimetindene formulation, equivalence pertaining to Q4 was established. However, high variability was observed for some rheology endpoints, especially for the different RP batches. Therefore, equivalence could not be established for Q3 as per EMA requirements. Can some rheology endpoints be waived? Can we establish reasonable criteria that are overall feasible for generic manufacturers and at the same time safe for the patient? An attempt was made to propose a wider acceptance range based on the inter-batch variability of the RP. For that, the rationale presented in the EMA guideline on bioequivalence for highly variable products was used.For the diclofenac formulation, Q3 equivalence was likewise not established. Q4 equivalence was only found for some batch combinations and when applying a wider acceptance criterion (75–133%). Furthermore, IVPT equivalence also failed to be demonstrated. Nevertheless, since the TP displays an equivalent pharmacokinetic profile compared to the RP, the observed Q3, Q4 and local availability differences are not expected to be clinically significant. This study draws attention to an effective search to determine the most appropriate strategy for assessing topical bioequivalence on a case-by-case basis.

Allergic rhinitis in children: a comprehensive approach to treatment

Prevalence of allergic rhinitis among chronic upper respiratory diseases in pediatrics is one of highest. Beside anti-inflammatory drugs (topical steroids, antileukotrienes, antihistamines), reliever therapies are important too in treatment of allergic rhinitis. Decongestant prescription in children should lasts no more than 7–10 days; combination of alpha1-adrenomimetic with topical antihistamines is one of possible ways to improve the efficacy, for example, the combination of dimetindene maleate with phenylephrine as nasal drops. We present the results of retrospective evaluation of 625 patients aged from 0 to 17 years with allergic rhinitis, diagnosed not less than 12 month ago. Among examined group, mild allergic rhinitis prevalence was 56.9%, moderate 37.2% and severe 5.9%. During the year all patients experienced 1754 exacerbations (on average, 2.79 ± 1.13 exacerbations per patient). Contact with allergen (35.3%) and respiratory infections (28.8%) were more prevalent reasons of exacerbation; non-specific trigger provocation (pungent smells, air humidity or temperature change etc.) (19.8%) and unknown reason (16.4%) of allerhttps://doi.org/10.21518/2079-701X-2022-16-1-184-189 gic rhinitis exacerbation were less prevalent. When treated with combined nasal drops of dimetindene maleate and phenylephrine median [Q25; Q75] duration of exacerbation was a bit shorter 7.94 [6.25; 17.15] days, than using other decongestants, but difference was statistically insignificant. Combined nasal drops were maximal clinically efficient among patients under 12 years old with exacerbations, caused by allergens contacts. We did not register any adverse events caused by decongestant treatment, during our study. Patients with allergic rhinitis should be provided with written action plan for the disease exacerbation. Using as reliever therapy combined nasal drops (dimetindene maleate and phenylephrine) registered for patients from 1 year old, decrease number of medicines and reduce allergic rhinitis exacerbations duration.

Current recommendations for the atopic dermatitis and food allergy treatment in children

Atopic dermatitis is the most common chronic childhood inflammatory skin disease. The chronic and recurrent nature of pediatric atopic dermatitis requires the use of active therapy for flares and maintenance therapy to promote the integrity of the skin barrier and prevent future flares. Systemic therapy is warranted for patients who have inadequate disease control (persistent severity and extent or significant impact on the quality of life) despite appropriate treatment with topical therapy and/or phototherapy. Over the past several decades, the prevalence of food allergy has continued to increase. It has become a significant health burden affecting 6–13% of the global population. There are two main types of medications that can be used to relieve the symptoms of the allergic reaction to food: antihistamines and adrenaline. Antihistamines can be used for food allergy prevention and treatment, in particular dimetindene maleate — Edermik.

The effectiveness of antihistamines in the treatment of atopic dermatitis in children

Histamine is one of the key endogenous mediators involved in the regulation of essential physiological and pathological processes in the human body. Its effects are implemented through several types of specific cell surface histamine (H)-receptors. H1-receptors are the most studied ones. The main clinical effects of their stimulation are vasodilation, bronchoconstriction, pituitary gland stimulation of hormone production, increased mucus production by the nasal glands, etc. Histamine H1 receptor antagonists of two generations are pathogeneticaUy justified agents for the treatment of most allergic diseases in accordance with the current clinical guidelines. The second-generation antihistamines that are devoid of sedative effects and are clinically more effective than the first-generation drugs have been currently introduced into the allergic disease treatment practice. They are the main drugs for the treatment of allergic diseases, especially in acute symptoms of the disease. Dimetindene maleate is the drug of choice for the symptomatic treatment of skin lesions, especially in infants. The article presents the result of the analysis of 26 out-patient medical records of infants (aged from 4 to 12 months) with a verified diagnosis of “atopic dermatitis, limited form, in the exacerbation phase”. A mild course of the disease was observed in 17 children, and a moderately severe course in 9 children. The duration of treatment was 7 to 16 days. Against the background of therapy (group 1), the following results were obtained: on day 3 of treatment the SCORAD-TIS index decreased to 16.4 ± 1.6 and on day 7 to 9.1 ± 1.3 points in children with a moderate course, and to 6.7 ± 0.8 and 4.1 ± 0.9 points in children with a mild course, respectively. In the children from group 2, the decrease in SCORAD-TIS was less significant: 19.5 ± 1.5 points on day 3, 12.2 ± 1.1 points on day 7 in children with a moderate course, respectively. Similar values decreased to 9.0 ± 0.9 on day 3, and to 6.9 ± 1.2 points on day 7 in children with a mild course of atopic dermatitis. The conducted analysis demonstrates the high clinical efficacy, good tolerance and the absence of tachyphylaxis of dimetindene maleate, drops. No side effects including those associated with anticholinergic properties (dry mouth, agitation) were identified.

The potential of dimetindene maleate inducing resistance to blast fungus Magnaporthe oryzae through activating the salicylic acid signaling pathway in rice plants.

Rice blast disease (Magnaporthe oryzae) is considered the most destructive rice disease all over the world. Dimetindene maleate is used in medication against allergic reactions in humans. Dimetindene maleate used to induce systemic acquired resistance (SAR) in rice (Oryza sativa L.) in order to protect rice plants from blast disease. Dimetindene maleate was not effective against fungus linear growth in vitro. In glasshouse conditions, dimetindene maleate significantly improved resistance at 25, 50, 125, 250, 500 and 1000 mg L-1 concentrations. Leaf blast severity reached 14.18% on plants treated with the most effective concentration of 125 mg L-1 compared with control plants. In field conditions during both seasons (2016 and 2017), 125 mg L-1 dimetindene maleate decreased the disease severity to 1.1% and 2.7%, respectively, after 30 days of treatment. Also, grain yield was increased to 13.27 and 12.90 t ha-1 in 2016 and 2017 seasons, respectively. Moreover, dimetindene maleate induces some of the indicators for salicylic acid and jasmonic acid pathways via gene expression. These genes include OsWRKY45, OsNPR1, AOS2, JAMYB and PBZ1 (OsPR10), recording 15.14-, 16.47-, 5.3-, 5.37- and 5.1-fold changes, respectively, 12-h postinoculation. The results overview investigated the effectiveness of dimetindene maleate for increasing rice resistance to blast disease through inducing SAR in rice plants under glasshouse and field conditions, which could be through the SA defense pathway by expression of genes (OsWRKY45 and OsNPR1). © 2021 Society of Chemical Industry.

Ефективність антигістамінних препаратів I покоління при лікуванні алергічних захворювань у дітей

У статті викладені сучасні відомості про клінічне застосування, ефективність та безпеку використання представника першого покоління Н1-антигістамінних препаратів — диметиндена малеату. Подана стисла характеристика препарату, вказані основні показники його фармакокінетики та фармакодинаміки. Акцентовано увагу на основних фармакологічних механізмах клінічних ефектів препарату. Проведено аналіз результатів клінічних досліджень із застосуванням диметиндена малеату при алергічних та інфекційних захворюваннях шкіри у дітей. Надані основні фармакологічні властивості та характеристика препарату Фенокіт, який нещодавно з’явився на фармацевтичному ринку України, обґрунтовані основні показання до призначення препарату.

Медикаментозная аллергия у детей: что нужно знать?

Реакции на лекарственные препараты являются причиной около 6,5 % всех госпитализаций. Они развиваются у 15 % пациентов, находящихся на стационарном лечении. Возможность их развития следует учитывать при дифференциальной диагностике, когда любая медицинская проблема возникает у человека, который принимает лекарства. У детей основной сложностью в диагностике лекарственной аллергии является дифференциация макулопапулезных высыпаний как реакции на лекарственное средство от вирусной экзантемы, которая часто наблюдается в этой возрастной группе. При лечении аллергических реакций первым шагом является немедленное прекращение действия причинного препарата. Избегание приема безрецептурных препаратов и употребления лекарств внутрь, если это возможно, важно с точки зрения профилактики лекарственной аллергии. При выборе альтернативного препарата следует учитывать перекрестную реактивность между препаратами с похожей структурой. На амбулаторном этапе для профилактики и лечения реакций на лекарственное средство могут быть использованы антигистаминные средства, в частности диметиндена малеат — Эдермик.

Biopharmaceutical and rheometric studies in the development of a gel composition with dimethindene maleate

Every year there is an increase in the number of cases of hypersensitivity to bites from various insects. A local allergic reaction to bites occurs within a few minutes and is accompanied by acute pain at the site of the bite, severe itching, hyperemia, the appearance of papules, tissue edema, and sometimes a small-point rash around. Considering the small number of drugs for local therapy of allergic manifestations and the unidirectional nature of their action, it is urgent to develop a drug containing the antihistamine dimethindene maleate and dexpanthenol, which plays the role of an anti-inflammatory, reparative and dermatoprotective substance.
 The aim. The aim of the study is to substantiate the delivery system of dimethindene maleate and dexpanthenol based on biopharmaceutical and rheometric research methods.
 Materials and methods. To determine the component composition of the active ingredient delivery system, the type of dimetindene maleate administration was substantiated by studying its solubility. As a delivery system for active pharmaceutical ingredients, hydrogels were considered, which were made using high-molecular compounds of various origins: a natural substance – xanthan gum, a semi-synthetic substance – gyroxypropyl methylcellulose, and a synthetic substance – carbomer. The rate of release of dimethindene maleate from hydrogels was estimated by studying the kinetics of release through a semipermeable membrane. The assessment of the viscoelastic properties of hydrogels was carried out by performing an oscillatory rheometry test, which makes it possible to quantitatively determine the viscous and elastic components, as well as to characterize the bioadhesive properties.
 Results. Based on the results of studying the solubility of dimethindene maleate in hydrophilic non-aqueous solvents, it was determined that propylene glycol is optimal for ensuring the introduction of a substance into hydrogel bases as a solution. As a result of studying the kinetics of the release of dimethindene maleate from hydrogels, it was found that the use of carbomer as a delivery system provides the release of 28.33 % of dimethindene maleate, xanthan gum – 25 %, hydroxypropyl methylcellulose – 7.33 %. When studying the viscoelastic properties by determining the values ​​of the storage modulus G', the loss modulus G" and the damping (attenuation) factor tg δ, it was found that the carbomer-based hydrogel is a viscoelastic solid, the xanthan gum and hydroxypropyl methylcellulose-based hydrogels are a viscoelastic liquid. Bioadhesion on the surface of the skin during use has the advantage of carbomer hydrogel.
 Conclusions. Based on the combination of biopharmaceutical and rheometric methods for substantiating the composition of the delivery system for dimetindene maleate and dexpanthenol, it is rational to use carbomer for further pharmacological and microbiological studies

Efficacy and safety of antihistamines in children with atopic dermatitis

Atopic dermatitis is one of the most common inflammatory diseases. This disease is characterized by severe itching, recurrent eczematous lesions and has a heterogeneous clinical picture. AD occurs in all countries, in both sexes, in different age groups. There has been a steady increase in the incidence of AD detection over the past three decades. The prevalence of AD symptoms in various regions of the Russian Federation (RF) ranged from 6.2 to 15.5%. There is no generally accepted classification of AD, the working classification of AD reflects the age dynamics, clinical and morphological forms, severity and stages of the course of the disease. Treatment of AD should be patient-centered and should include prevention of individual trigger factors, restoration of the skin barrier, and a stepwise and gradual approach to reduce inflammation based on the severity of the disease. mGCS are the first-line treatment for exacerbations of AD. Topical calcineurin inhibitors are tacrolimus and pimecrolimus. Pimecrolimus is indicated for the treatment of mild to moderate AD, and tacrolimus is indicated for moderate to severe AD. Tacrolimus and pimecrolimus are characterized by low systemic absorption, they do not cause skin atrophy and do not affect the function of the hypothalamic-pituitary-adrenal system. Systemic corticosteroids should be used only in exceptional cases for short-term treatment of an exacerbation or when starting another systemic therapy. The therapeutic value of 1st generation antihistamines lies in their sedative properties by normalizing nighttime sleep and reducing the intensity of itching. Dimetindene maleate is an effective and safe treatment for relieving symptoms of pruritus and normalizing sleep in patients with AD. Dimetindene maleate has a high safety profile and can be prescribed from 1 month of age.

Analytical investigation of ternary mixture of phenylephrine hydrochloride, dimetindene maleate and benzalkonium chloride using validated stability indicating HPLC-DAD method

A stability-indicating high performance liquid chromatography method with diode array detection (HPLC-DAD) was developed and validated for simultaneous determination of phenylephrine hydrochloride (PHR), dimetindene maleate (DMD) and benzalkonium chloride (BZM) in nasal drops and gel dosage forms. Effective liquid chromatographic separation was accomplished by employing Venusil XBP Cyano column (4.6 × 250 mm, 5 µm particle size) with gradient elution of the mobile phase consisting of buffer solution of potassium dihydrogen phosphate (0.025 M) and sodium 1-butane sulfonate (SBS) (0.025 M) (adjusted to pH 6.0) and acetonitrile. Peak areas of PHR, DMD and BZM at 271, 256 and 206 nm, respectively were measured and correlated to their concentrations. Peaks of PHR and DMD eluted at retention times 3.76 and 9.06 min, respectively, while BZM eluted as a couple of peaks at 11.88 and 12.51 min. The proposed HPLC procedure was carefully validated in terms of system suitability, linearity, ranges, precision, accuracy, specificity, robustness, detection and quantification limits. The linearity range for both PHR and BZM was 10–400 μg/mL and DMD was 5–300 μg/mL with correlation coefficients >0.9999. The studied compounds were subjected to stress conditions of neutral, acidic and alkaline hydrolysis, oxidation and thermal degradation. Good resolution of the three compounds from their forced degradation products proves specificity and stability-indicating merits of the proposed method. In addition, resolution of the three drugs under investigation from some pharmaceutical compounds of different medicinal categories showed the high specificity of the described method.

Хронічний свербіж при захворюваннях шкіри в дітей

The article presents modern information on the clinical use and safety of the first-generation H1-antihistamine – dimetindene maleate. Pruritus (itch) mediators act both peripherally (histamine, proteases) and centrally (opioids) and has several mechanisms. Pruritus is the dominant symptom of skin diseases; almost all inflamamatory skin diseases can have associated pruritus. Doctors have focused on the almost one dermatosis with signs of itching – atopic dermatitis. At the same time, the range of diseases, both dermatological and systemic, accompanied by itching, is much wider.

Adhesion Prevention to Polypropylene Meshes Using Combined Icodextrin Four Percent and Dimetindene Maleate

BackgroundThe use of surgical meshes in ventral hernia repair has significantly reduced hernia recurrence rates. However, when placed intraperitoneally prosthetic materials can trigger the development of peritoneal adhesions. The present experimental study evaluated the combined icodextrin 4% and dimetindene maleate treatment in preventing peritoneal adhesion formation to polypropylene and titanium-coated polypropylene meshes. Materials and methodsSixty female white rabbits were divided into four groups. A 2 × 2 cm piece of mesh was fixed to intact peritoneum in all animals through a midline laparotomy. A lightweight polypropylene mesh was implanted in groups 1 and 2 and a titanium-coated polypropylene mesh in groups 3 and 4. Groups 2 and 4 were treated, intraoperatively, with intravenous dimetindene maleate (0.1 mg/kg) and intraperitoneal solution of icodextrin 4% (20 mL/kg) and for the next 6 d with dimetindene maleate intramuscularly. The observation period lasted 15 d. Adhesion scores, percentage of mesh affected surface, tissue hydroxyproline levels, and tissue histopathology were examined. ResultsAll animals in group 1 and 57% of animals in group 3 presented postoperative adhesions. The combination of antiadhesives significantly reduced the extent and severity of adhesions as well as the hydroxyproline levels in groups 2 and 4 compared with groups 1 and 3. On microscopic evaluation, animals in group 1 exhibited higher inflammation scores compared with group 2, whereas animals in groups 2 and 4 had better mesotheliazation compared with groups 1 and 3. ConclusionsThe combined administration of icodextrin 4% and dimetindene maleate reduces the extent and severity of adhesions and may be successfully used to prevent adhesion formation after mesh intraperitoneal placement.

Purity Indicating TLC Method for Quantitative Determination of Phenylephrine and Dimethindine Maleate in Presence of Dimethindine Maleate Impurity: 2-ethyl pyridine in Nasal Gel

The aim of this work was to establish, optimize and validate a sensitive, selective and accurate thin layer chromatographic (TLC) method for determination of Phenylephrine (PHE), Dimetindene maleate (DM) and its major toxic impurity; 2-ethyl pyridine (EP), in raw material and nasal gel. The proposed method was applied for analysis of PHE, DM and EP over the concentration range of 1.00–10.0, 0.50–8.00 and 2.00–20.0 µg/band, respectively. The method is based on the separation of three components followed by densitometric measurement of the separated peaks at 254 nm. The separation was carried out on silica gel TLC F254 plates, using toluene: acetone: isopropyl alc.: ammonia (5.3: 2.7: 1.8: 0.4, by volume) as a developing system. The suggested method was validated according to International Conference on Harmonization guidelines and can be applied for routine analysis in quality control laboratories. The results obtained by the proposed method were statistically com-pared with the official method revealing high accuracy and good precision.

Development of the method for quantitative determination of phenylephrine hydrochloride in the combined drops

The work is devoted to development of the method for quantitative determination of phenylephrine hydrochloride in the combined nasal drops Gripocitron Rinis. Combination of phenylephrine hydrochloride possessing the vasoconstrictor action with dimetindene maleate having the antihistaminic action formulated into drops decreases nasal discharge and helps to clear the nasal passages without disturbing physiological functions of the ciliated epithelium and mucous membrane. It has been found that the quantitative content of phenylephrine hydrochloride in the combined nasal drops can be determined by spectrophotometry in the ultraviolet spectrum at the wavelength of 296 nm. The method proposed demonstrates the possibility of phenylephrine hydrochloride determination in combined drops in the presence of another active pharmaceutical ingredient – dimetindene maleate, which has the absorption minimum in sodium hydroxide solution at this wavelength. The influence of the additional ingredient – benzalkonium chloride drops on the nature of the absorption spectrum of phenylephrine hydrochloride is recommended to eliminate by the action of potassium dichromate solution. The optimal amount and concentration of solutions of sodium hydroxide and potassium dichromate, the analytical band have been determined. Validation of the given method has been carried out according to the following validation characteristics: linearity (a = 4.34 ≤ maxa 5.10%, b = 1.04), accuracy (0.52 ≤ maxδ 1.02%), convergence (1.07% ≤ max Δas 3.20%) and the correlation coefficient r, which is 0.9997. It has been found that the method suggested for determination of phenylephrine hydrochloride in nasal drops is precise, accurate, reproducible and linear, and it allows recommending it for using in pharmaceutical analysis. Phenylephrine hydrochloride is a known sympathomimetic providing a selective stimulating effect mainly on postsynaptic α-adrenergic receptors [4, 5]. Being a decongestant with a moderate vasoconstrictor action phenylephrine contains in a number of nasal drugs for local application, such as Nasol Baby (phenylephrine hydrochloride), Nasol Kids (phenylephrine hydrochloride with eucalyptol and benzalkonium chloride), Vibrocil and Gripocitron Rinis (phenylephrine hydrochloride with dimetindene maleate and benzalkonium chloride), which are used for symptomatic treatment of nasal congestion, acute and chronic rhinitis, allergic rhinitis, sinusitis, acute otitis. The search of safe and effective monocomponent and combined decongestant nasal drops for local application with phenylephrine hydrochloride actualizes development and standardization of methods for quality control of this substance in the presence of other active pharmaceutical ingredients (API) [3, 6, 7, 9]. Materials and Methods The object of the research was Gripocitron Rinis, nasal drops, 15 ml. The active substances were phenylephrine hydrochloride equivalent to 2.5 mg of phenylephrine, dimetindene maleate 0.25 mg; excipients were citric acid, monohydrate; anhydrous sodium hydrogen phosphate; sorbitol (Е 420); benzalkonium chloride; peppermint oil; purified water as needed. The reference standard (RS) of the substance of phenylephrine hy

Quantitative Analysis of Dimetindene Maleate in Dosage Forms by Ion-pair Reversed- Phase HPLC

The formulations of Dimetindene Maleate as capsule, drop and gel and their methods of analysis are still unavailable in international Pharmacopeia. In this work ion-pair reversed- phase HPLC method was developed for the determination of Dimetindene Maleate in its dosage forms,which can be used for the assay of capsule or tablet, drop and gel.The separation of Dimetindene Maleate was performed in about 10 minutes with high efficiency using ODS column 25cm and a mobile phase consists of methanol 40 % in distilled water containing 0.02% 1-heptane sulfonate and adjusted with sulfuric acid to pH (3.5).Thelinearity of this HPLC method was proved and a straight line relationship was obtained between the peak areas and the different concentrations of Dimetindene Maleate standard solution in the range (1-8)μg/ml with confidence limit of 0.998 and the RSD was not more than 1.2%. In addition, this method was found to be suitable for stability study of dimetindene preparations and for dissolution test of capsules and tablets of dimetindene as well.

Role of Histamine in Altering Fluid Recycling in Normal and Post-Traumatic Rabbit Peritoneum

This study aims to investigate if histamine induces electrochemical alterations in the normal and post-traumatic peritoneum. Peritoneal rabbit specimens were obtained before surgery and 10 days post-operatively and were mounted in Ussing chambers. Histamine solutions were added facing the intra-peritoneal and outer-peritoneal surface. Dimetindene maleate-, cetirizine-, and ranitidine-pretreated specimens were used to investigate histamine receptor involvement, whereas amiloride- and ouabain-pretreated specimens were used to investigate ion transportation blockage involvement. Trans-mesothelial resistance (R(TM)) was determined. Histamine-increased R(TM) intra-peritoneally and decreased it outer-peritoneally. A less intense effect was induced in post-traumatic specimens. Dimetindene maleate, cetirizine, amiloride, and ouabain totally inhibited this effect, whereas ranitidine only had a partial effect. Histamine induces electrochemical alterations in the normal and post-operative peritoneum. This effect is mediated by interaction with histamine receptors, hindering the normal process of ion trans-mesothelial transportation.

Matrix Metaloproteinase-2 and -9 Serum Levels as Potential Markers of Intraperitoneal Adhesions

ABSTRACTObjective: To assess the value of matrix metalloproteinases-2 (MMP-2) and -9 (MMP-9) as prognostic serum markers for intraperitoneal adhesions. Background: Postoperative adhesions are associated with serious complications responsible for increased patient's morbidity. Methods: Forty-eight rabbits were used and randomized into groups A, B, C, and D. Abdominal laparotomy and experimental adhesion formation model was carried out. In group A, 60 mL of N/S 0.9% were instilled intraperitoneally, in group B 60 mL of icodextrin 4% were instilled intraperitoneally, in group C 0.1 mL/kg of dimetindene maleate were administered intravenously, and in group D both agents were administered. Prior to euthanasia 0.5 mL of blood was obtained. The type, the surface area of adhesions, and serum concentration of MMPs were assessed. Results: The mean surface area and Zuhlke classification of adhesions of groups B, C, and D has been proved to be significantly lower compared to group A. Serum MMP-2 levels were significantly higher in groups B and D than in group A, while group D was higher when compared to group C. Serum MMP-9 levels were significantly higher in group D compared to groups A, B, and C. Serum MMP-9 was the most accurate test to differentiate between animals with and without adhesions with a sensitivity of 81.8% and a specificity of 100% at a cut-off point of 21.5 (AUC = 0.934). Conclusions: The administration of icodextrin 4% and dimetindene maleate seems to prevent postoperative adhesion formation. Serum levels of MMP-2 and MMP-9 may serve as prognostic markers to identify postoperative adhesions.

Effect of histamine on the electrophysiology of the human parietal pleura

IntroductionHistamine is involved in the pathogenesis of numerous diseases and regulates the permeability of different tissues. The aim of this study is to investigate the effects of histamine on the electrophysiology of human parietal pleura and the underlying mechanisms involved. Materials and methodsPleural specimens were obtained from patients subjected to thoracic surgery and were mounted in Ussing chambers. Histamine solutions (1μM to 1mM) were applied in native and pretreated specimens with dimetindene maleate, cetirizine, ranitidine, amiloride and ouabain. Trans-mesothelial resistance was determined (RTM). ResultsHistamine induced a rapid RTM increase on the mesothelial (p=0.008) and a decrease on the interstitial surface (p=0.029). This effect was dose-dependent and was totally abolished by dimetindene maleate, cetirizine and amiloride and partially by ranitidine and ouabain. ConclusionsHistamine induces acute electrochemical changes in human pleura mainly via interaction with the H1 and partially with the H2 histamine receptors. It also interferes with trans-cellular permeability and therefore may participate in pleural fluid recycling.

Permeability Alterations after Surgical Trauma in Normal Rabbit Peritoneum

Background: To investigate whether surgical trauma in a rabbit adhesion formation model and the administration of normal saline (N/S), icodextrin (ID) and/or dimetindene maleate (DM) changes the permeability of the normal rabbit parietal peritoneum. Materials and Methods: A total of 45 female rabbits were operated on for adhesion formation and were euthanized 10 days later. In some rabbits, ID or N/S was instilled intraabdominally during operation, whereas in others DM was infused intravenously. In others, ID plus DM or no agent was used. Specimens were obtained postoperatively and were mounted between Ussing chambers. Amiloride was used to investigate Na⁺ channels. Transmesothelial resistance (R_TM) was determined as a permeability indicator. Results: Amiloride increased the R_TM of both surfaces. Surgical trauma increased R_TM and partially inhibited the effect of amiloride. ID and N/S increased R_TM and inhibited the effect of amiloride. Use of DM did not change R_TM and did not inhibit the effect of amiloride. Use of ID plus DM slightly increased R_TM, but the effect of amiloride was blocked. Conclusions: Surgical trauma impairs the permeability of the normal rabbit parietal peritoneum. ID or N/S surmounted this effect, but DM did not, suggesting that surgical trauma is a diffuse process. Antiadhesion measures influence peritoneal physiology.