Moldovan Medical Journal

12-15

Authors: Vasile Musteata, Valentina Stratan, Larisa Catrinici, Larisa Musteata, Cristina Dudnic

Background: Chronic myeloproliferative hemopathies (CMPH) as a whole are the most common chronic leukemias in the elderly in the structure of morbidity by hematological malignancies with primary bone marrow involvement, being characterized in the advanced stages by a severe, recurrent evolution and unfavorable prognosis, with negative socio-economic impact. Material and methods: A clinical, analytical, and descriptive study was carried out along with the narrative review of the international literature on the subject. The study enrolled 91 elderly patients with different phases of chronic myeloid leukemia (CML), primary myelofibrosis (PMF) and polycythemia vera (PV), who were followed up and treated at the Institute of Oncology in the period of 1995–2020. According to the impact score, 25 relevant primary sources were identified and selected having a scientific, reproducible and transparent approach to the relevant subject, followed by data extraction and analysis. Results: The overall one- and 5-year survival in patients aged greater than or equal to 60 years old treated with tyrosine kinase inhibitors (TKIs) was 97.6 and 79%, being lower as compared with the same indices in the totality of CML. In elderly PV patients the overall 5-and 10-year survival made up 93.5% and 76.4%, being lesser than registered in all patients with PV. As reported in the recent references, a significant rate of patients with CMPH underwent reduced working hours, discontinued employment, and medical disability: PMF – 38%, 35%, 33%, and PV – 33%, 28%, and 15%, respectively. Conclusions: The long-term treatment results in elderly patients with CMPH fail compared to those in the CMPH totality, due to the development of age-related diseases and vascular accidents caused by leuko- and thrombocytosis.

21-24

Authors: Ana Popa, Anatolie Negara, Gabriela Soric, Ana Popescu

Background: The new SARS-CoV-2 coronavirus affects a large number of people worldwide, and the elderly are particularly affected because of their vulnerability. Thus, the elderly patients and those with comorbidities have an increased risk of developing a severe disease and show an increased mortality rate. Although they may show mild symptoms of illness and low-grade fever in the early days, they may worsen clinically rapidly, requiring ongoing monitoring. Material and methods: The prospective study was performed on a group of 96 patients (mean age 61.41 ± 3.42 years), with a predominance of men, hospitalized in the Holy Trinity Hospital of Chisinau who met the clinical case definition and were laboratory case-confirmed with COVID-19. Patients were clinically and paraclinically investigated according to the WHO Provisional National Clinical Protocol for COVID-19 infection reporting. The data were statistically processed by the Statistics 10 program. Results: Of the 96 patients with COVID-19, 85 (88.54%) reported at least one had a comorbidity. The prevalence of comorbidities was the following: chronic coronary syndromes (40.1%), hypertension (39.7%), diabetes (16.04%), chronic obstructive pulmonary disease (17.3%), malignancy (13.04%), cerebrovascular disease (10.6%), chronic kidney disease (4.3%) and viral hepatitis B (1.8%). Severe cases of the disease were revealed – 58, medium severity – 38 cases. All critical cases resulting in death (7.29%) showed comorbidities with respiratory symptoms, as well as with the onset of acute respiratory failure. Conclusions: The elderly, male gender and the presence of comorbidities in patients with COVID-19 determine the severe course of the disease and an increased mortality rate.

33-35

Authors: Anastasia Buza, Sergiu Parii, Cristina Butovscaia, Daniela Galea-Abdusa, Luminita Radulescu, Ghenadie Curocichin

Background: Guanine deletion 35delG in GJB2 exon 2 is the pathogenic mutation responsible for up to 70% of cases of congenital non-syndromic sensorineural hearing loss (NSHL) among Europeans. The early molecular diagnostic of hearing loss nature has become important while considering the cochlear implants. The purpose of this study was to establish the frequency of 35delG deletion in GJB2 gene among patients with severe NSHL and its prevalence among Moldovan residents with normal hearing. Material and methods: 40 patients with congenital bilateral profound NSHL and 300 individuals with normal hearing were examined for deletion 35delG, by using Custom TaqMan SNP genotyping Assay. Results: 12 (30%) patients with homozygous genotype for 35delG mutation were identified, whereas 8 patients (20%) were heterozygous. The study reported 4 (1.33%) carriers of 35delG mutation among 300 Moldovan individuals with normal hearing. Conclusions: The present study results suggest a need for including the 35delG molecular testing into the national program of neonatal screening of hearing loss. Considerations on the genetic carrier testing should be made in genetic counseling and family planning.

45-48

Authors: Constantin Toncoglaz

Background: Uterine arteriovenous malformations (AVM) are extremely rare entities, with less than 100 cases reported in the literature. Synonyms for AVM are arteriovenous fistula, branched aneurysm, hemangioma, pulsating angioma, and cavernous angioma. Incidence of uterine AVM according to the studies of O´Brien et al., who identified uterine AVM in 21 women based on 464 pelvic ultrasound examinations for uterine bleeding, reported an incidence of 4.5%. However, Yazawa et al. examined 959 patients prospectively and observed an incidence of 0.6% of uterine vascular malformation on ultrasound examination The etiology of uterine AVM can be congenital or acquired. The purpose of the study was to raise awareness on the existence of these injuries and understanding their risk factors, to study different treatment methods, especially conservative or minimally invasive ones, as well as methods for diagnosing of these malformations. The following key words were used as a search engine: uterine arteriovenous malformation, uterine malformation, circoid aneurysm. Only full-text articles were analyzed. Conclusions: Uterine AVM is a rare cause of uterine bleeding. However, it is a potentially life-threatening disorder in which patients present with vaginal bleeding that may be profuse and cause hemodynamic instability.

52-56

Authors: Elena Condratiuc

Background: The management of epilepsy can be reviewed in a multidimensional way, medical, psychotherapeutic, familial and social. In this regard, we are talking about the position given to the patient suffering from epilepsy.From a psychopathological point of view, there is a system of interactions between crisis and personality based on confusional anxieties, related to ambiguity and the feeling of crisis for the subject. The psychotherapeutic understanding of the patient suffering from epilepsy is situated in a bio-psycho-familial and social context. Whether it is the first, the second, or the next crises, they point out that there is an intrapsychic trauma. Conclusions: System of interactions between epilepsy, the patient and the environment contributes to the creation of the framework that will provide opportunities to help the patient. Psychotherapy sessions allow the patient to reintroduce the crisis in his history. The description of psychological experiences that are associated with the evolution of epilepsy symptoms, will allow us to form an idea about the influence of psychic trauma on the clinic and the dynamics of epilepsy, which could help identify an approach to the patient’s adaptation.

63-67

Authors: Gheorghe Placinta, Valentina Vorojbit, Victor Pantea, Lilia Cojuhari, Valentin Cebotarescu, Lidia Placinta, Dan Croitoru

Background: Clostridium difficile (CD) infection is widespread throughout the world, showing an increased incidence over the recent years and may cause severe forms of disease. This infection most commonly affects patients whom were administered antibiotics. An increased resistance to commonly used antibiotics is associated with Clostridium difficile infection (CDI). CD has a generally recognized infectious potential on a clinical ground. CDI is unpleasant and may sometimes cause serious bowel disorders that are usually treated with another course of antibiotics. The evolution of CD infection depends on the individual characteristics of the patient along with risk factors, associated diseases as well as the particularities of the recommended treatment. However, even under the conditions of a correct and complete treatment the risk of the disease relapse is estimated to occur depending on risk factors. Many clinical instruments that are designated for the purposes to treat non-infectious diseases can be useful in estimating the severity of an infection. This review is important for understanding the abusive and irrational prescription of various groups of antibiotics, often unjustified, including the ones used in the treatment of an infection with SARS-CoV-2. Conclusions: These infections mostly occur in people aged 65 and older that receive medical care, including antibiotics administration, people with a long-term hospital stay, people with a weakened immune system or with a previous CD infection. The following measures, in order to reduce the risk of CDI in patients, should be considered: hand hygiene, avoidance of unnecessary administration of antibiotics – the antibiotic treatment is recommended only if it is prescribed by an experienced specialist, avoidance of unnecessary administration of drugs that reduce gastric acidity, because it favors the invasion of the gastrointestinal tract with CD.

9-14

Authors: Diana Calaras, Doina Rusu, Aliona David, Victor Botnaru

Background: Interstitial lung diseases (ILD) are a group of disorders that are generally thought to commonly share a restrictive ventilatory defect and reduced diffusing capacity for carbon monoxide (DLCO). The aim was to find distinctive features of the pulmonary function tests (PFT) results in different types of ILD. Material and methods: We conducted a retrospective study of 40 consecutive patients with ILD admitted to the Institute of Pthisiopneumology, Chisinau, the Republic of Moldova, during January 2019 – February 2020. The cohort included 10 cases of sarcoidosis patients, 8 cases of idiopathic pulmonary fibrosis (IPF) patients, 7 patients with nonspecific idiopathic interstitial pneumonia, 9 cases with hypersensitivity pneumonitis (HP) and 6 histiocytosis cases. All patients have been evaluated by pulmonary function tests (PFT), 6 minutes walk test, Medical Research Council scale for dyspnea, etc. Results: Overall, we found normal mean spirometry parameters, a slightly increased mean residual volume (127.5±42.1), a mildly decreased mean total lung capacity (88.8±22.3) and moderately reduced DLCO (52.6±21.5). We found a dominant restrictive pattern in 75% of patients, and obstruction only in 7.5% when we used spirometry parameters. When we applied the bodyplethismographic values, we have found that an air-trapping pattern was identified in 32.5% cases of patients. This pattern has been identified in 1/3 of HP patients and in 10% of sarcoidosis patients. Conclusions: PFT can help identifying individual features of different types of ILD being able to show even obstructive changes in a group of diseases thought to be strictly restrictive.

19-25

Authors: Oxana Munteanu, Doina Rusu, Diana Tambala, Victor Botnaru

Background: Immunodeficiencies should be suspected in cases of primary identified bronchiectasis in adults. Moldova is among the countries with a continuous increase in the number of HIV-infected adults. Impaired immune system and chronic inflammation contribute to the progression of bronchiectasis in HIV patients. The aim of the study was to present the clinical, imaging, bacteriological peculiarities and outcomes in adult patients with bronchiectasis and HIV/AIDS infection. Material and methods: This case series involved 11 patients with HIV/AIDS and bronchiectasis, selected from a prospective study conducted on 490 patients diagnosed with non-cystic fibrosis bronchiectasis in a tertiary care hospital, between 2015–2019. Clinical, microbiological and radiological data, associated comorbidities and severity scores were analysed. Statistical analysis was performed using the SPSS 23 program. Results: The mean age was 39 years (range 25-65 years), with a male predominance (54%). A CD4 count <200 cells/mm3 was identified in 6 cases. The mReiff score (6.8±4.6) showed a significant correlation with Bhalla score (9.72±4.5), r=0.66 (p <0.05). BSI score (11.7±3) reflects better the severity of the disease, showing a significant correlation with the Bhalla imaging score (r=0.62, p<0.05). Assessing the impact of comorbidities (BACI index 5.4±4.3 and Charlson index 6.9±1.3), the BACI index better reflected the severity of the disease in this group of patients, demonstrating a strong correlation with BSI (r =0.62, p<0.05). Only 3 patients (27%) were over 1-year follow-up. Conclusions: Bronchiectasis is one of the common pulmonary manifestations of HIV/AIDS infection, being responsible for a number of chronic respiratory symptoms and the risk of premature death.

30-34

Authors: Stela Adauji, Galina Croitoru, Vladimir Safta

Background: The automated evidence of any systemic personal data represents an important tool to provide good functionality of that system. It absolutely refers to the pharmaceutical system as well, which is a part of the health system. Purpose of the study: To elaborate and argue the need to implement the automated information system of pharmaceutical staff management (AIS PSM) within the health system of the Republic of Moldova. Material and methods: Statistical data on the pharmaceutical system; systemic approach by applying statistical analysis, and system programming methods. Results: The automated system contains and ensures the processing of the following categories of personal data: first name, last name; date of birth; gender; occupation; graduation diploma; graduated institution; the employee workplace /the pharmaceutical company address; continuous education training; professional association membership fee; special references. The confidentiality of the personal data and the possibility of extending the categories of data is ensured, as well as the possibility of integration the developed system in the national health systems and statistical systems. Recommendations regarding the need of implementation of the AIS PSM in pharmaceutical units were worked out. Conclusions: In the Republic of Moldova, the automated pharmaceutical staff management information system was developed and proposed, though its implementation was largely discussed. There were also arguments on the recommendations to ensure the functionality of the system by elaborating sequential diagrams.

39-44

Authors: Gheorghe Ciobanu, Victoria Melnicov, Nasarulla Nasarudeen

Background: According to the WHO, over 15 million people worldwide suffer from stroke annually, 5.5 million die and 5 million become permanently disabled. According to the latest WHO data published in 2017, Stroke Deaths in the Republic of Moldova made up 15.87% of total deaths. Material and methods: A retrospective hospital-based study was conducted at the clinics of the Department of Emergency Medicine of Nicolae Testemitanu SUMPh and at the tertiary Care Hospital of Assam Medical College, the Republic of India, during January 01, 2019 – December 31, 2019. Two groups of patients were enrolled in the research, viz. lot 1 (80 patients) treated in the Institute of Emergency Medicine of the Republic of Moldova and lot 2 (80 patients) treated at the tertiary Hospital of Assam Medical College, India. The purpose of the study was to assess the major risk factors for developing ischemic stroke, as well as to evaluate the impediments in providing patients with modern treatment strategies among adult population. Results: The study group included 44 (55.0%) males and 36 (45.0%) females. 66 patients (83.0%) suffered an ischemic stroke and 14 patients (17.0%) had hemorrhagic stroke. The risk factor providing access to modern treatment strategies in acute stroke cases is taken in consideration. Conclusions: The high incidence of stroke suggests that primary prevention strategies used in the Republic of Moldova and the Republic of India are either not widely implemented or not sufficiently effective.

51-53

Authors: Victor Nemtan, Evghenia Hacina, Galina Topciu, Elena Manole, Vitalie Lisnic, Majda Thurnher, Rüdiger von Kummer

Background: Immunocompromised status keeps on being a challenge for a physician, especially in the context of the coronavirus disease – 19 (COVID-19) pandemic. The predominant clinical presentations are related to the respiratory system, but neurological manifestations are recognized increasingly. Cases of myelitis associated with the new coronavirus infection have already been published, but no cases of HIV-positive patients with myelitis and COVID-19 have been reported yet. Material and methods: This study described a clinical case of a human-immunodeficiency virus (HIV) – positive patient, who developed an acute transverse myelitis with confirmed SARS-CoV-2 infection. Results: Magnetic Resonance Imaging examination showed longitudinally extensive spinal cord abnormality, and laboratory tests confirmed SARS-CoV-2 infection. The patient responded to methylprednisolone pulse therapy, followed by oral corticosteroids and therapeutic plasma exchange. Conclusions: Continuing pandemic and the expectation that a large part of the world population will be infected suggest that the number of patients with neurological manifestations could become large. Curious neurologic constellations can appear which complicate the diagnostic process and treatment in certain patients.

62-67

Authors: Adriana Botezatu, Nicolae Bodrug, Viorel Istrate

Background: Independent risk factors for chronic atrophic gastritis, gastric intestinal metaplasia and gastric cancer are: Helicobacter pylori infection (especially virulent CagA strains), genetic factors (advanced age, reflecting the duration of Helicobacter pylori infection, male gender, family history of gastric cancer in first-degree relatives), gastric ulcer, biliary reflux, acute or chronic gastric inflammation, smoking, alcohol consumption, prolonged use of proton pump inhibitors or non-steroidal anti-inflammatory drugs, diet low in fruits, vegetables and vitamin C, excessive salt intake and consumption of canned foods with salt). Helicobacter pylori infection and inflammatory cells induce the expression of inducible nitric oxide synthase in the gastroduodenal mucosa, which causes various clinical lesions (duodenal ulcer, gastric ulcer and chronic gastritis without ulcer). Another important condition associated with Helicobacter pylori infection is gastric cancer. Overproduction of nitric oxide, through inducible nitric oxide synthase and oxidative stress, is a genotoxic and mutagenic metabolism which plays a crucial role in the process of gastric carcinogenesis. Conclusions: Chronic atrophic gastritis is considered a multifaceted condition because it can manifest itself through a variable spectrum of nonspecific gastric and extra-gastric symptoms, with an overlap of the clinical features of the two entities of chronic atrophic gastritis – autoimmune and associated with Helicobacter pylori infection. Thus, in contrast to the classic perception of a silent condition, patients with chronic atrophic gastritis report a wide range of gastrointestinal symptoms, ranging from dyspeptic symptoms to those of gastroesophageal reflux.

12-17

Authors: Elena Donici, Vladimir Valica, Livia Uncu

Background: The isohydrafural and fluocinolone acetonide combined ointment contributes to the diversification of the treatment of dermatitis and psoriasis associated with bacterial infections. Complex stability studies were performed to ensure the quality of it during the shelf life. The objective of this study was to determine the stability and shelf life of the combined ointment containing isohydrafural and fluocinolone acetonide. Material and methods: Three series of ointment were tested by the real-time method (temperature 25± 2°C; relative humidity 60 ± 5%) over a period of 30 months, periodically determining the appearance, homogeneity, pH, viscosity, identity, purity and assay. OHAUS DV215 CD electronic balance, Shimadzu LC-20 A HPLC, Consort C861 pH meter and Fungilab rheometer were used to fulfil the study. Results: At 24 months after storage, the three series of the ointment proved to be homogeneous, with a pH between 5.76 and 5.53. The rheograms showed a pseudoplastic behavior, with a slight thixotropy, with a viscosity close to 70 cP. The active substances were detected at the characteristic retention times: isohydrafural – 3 minutes, fluocinolone acetonide – 5.9 minutes and also no additional peaks occurred. The content of active substances was within the permitted limits: 0.098-0.11% (m/m) for isohydrafural and 0.0248-0.025% (m/m) for fluocinolone acetonide. Conclusions: The combined ointment containing isohydrafural and fluocinolone acetonide was found to be stable under the storage conditions stipulated in the quality specification. The established shelf life is 24 months.

23-26

Authors: Anna Benea, Cristina Ciobanu, Maria Cojocaru-Toma, Nicolae Ciobanu

Background: Carotenoids have played a significant role in reducing the risk of chronic diseases. The most studied in this regard is β-carotene, present in species of Tagetes and Calendula genus. Objective of the study: Comparative analysis of β-carotene content in liquid and dry flowers extracts of Tagetes and Calendula species, cultivated in the collection of the Scientific Center for the Cultivation of Medicinal Plants of Nicolae Testemitanu SUMPh. Material and methods: Dry extracts of flowers harvested in the budding-flowering phase, were obtained by repeated maceration and rotary evaporation, subjected to phytochemical evaluation by thin-layer chromatography (TLC) and UV-VIS spectrophotometry, equivalent to β-carotene. Results: Beta-carotene was identified by TLC in hexan-ethyl acetate (50:50, v/v), retention factors were established. Caratenoid content (mg%) varied as follows: in T. patula L. (75.34±2.15), T. erecta L. (21.97±0.84), C. officinalis L. variety Natali (13.09±3.23), C. officinalis L. variety Diana (12.39±1.98), C. officinalis L. local population (10.99±0.06). The carotenoids content ranged in the dry extracts as well, determined in the highest amount in T. patula L. flowers (137.87±2.18 mg%). Conclusions: This study demonstrated the opportunity for further research of Tagetes and Calendula varieties that could serve as sources of carotenoids for obtaining antioxidant phyto-pharmaceuticals.

35-42

Authors: Ecaterina Mazur, Martin Schmid, Livia Uncu

Background: Compatibility determination between active pharmaceutical ingredients (APIs) in fixed-dose combinations is an indispensable step in the elaboration. High-performance liquid chromatography provides information on possible interactions between APIs and their related interaction products. The purpose of the present study was to investigate the compatibility of potassium orotate in combination with spironolactone by a HPLC method. Material and methods: The detection was carried out using Liquid Chromatograph Agilent 1100 with UV-VIS detector and a RP-18 reversed column (250*4 mm, 5 μm), mobile phase of acetonitrile: phosphate buffer solution (pH=4.0) with the ratio 1:49 and 1:1, at flow rate 1 and 1.5 mL/min, injection volume 20 μL; potassium orotate and spironolactone substances were provided by Sigma Aldrich, USA. Results: Due to the developed method both separation and simultaneous qualitative and quantitative determination of APIs in the mechanical mixture were carried out. Spironolactone: retention time 6.9 min, concentration 98.1% (±0.21); potassium orotate: retention time 3.06 min, concentration 91.67% (±0.15). There were just well-separated symmetrical peaks of APIs and no additional peak in the chromatograms. Conclusions: There is compatibility between APIs. Further studies will be performed by other methods (DSC, FT-IF Spectrometry) to confirm the obtained result.

49-53

Authors: Elena Zgircu

Background: To ensure rare disease patients with medicines is a challenge for the health system. Treatments for rare diseases are very expensive, so the main financial burden for providing patients with medicines lies with the state. The objective of the study was to identify the aspects related to the optimization of process of assurance with medicines the patients with rare diseases. Material and methods: Retrospective study was performed using systemic analysis methods. Data were collected and processed with reference to health programs in the field of rare diseases and centralized public procurement. Results: The mechanism by which “rare” patients are provided with medicines and major problems related to was analyzed. The National Program “Combating rare diseases” represents the first stage by identifying the rare diseases that most frequently affect patients in the Republic of Moldova. Treatment options and annual medicines requirements are set in accordance with national clinical protocols and international guidelines recommendations, the number of patients on the doctor’s records, as well as statistical data. Conclusions: Major problems in ensuring medicines to patients with rare diseases have been identified. The need of medicines is ensured by centralized public procurement, from the financial resources of the state budget, which were analyzed for the period of years 2018-2020.

61-64

Authors: Ana Podgornii, Vladimir Valica, Serghei Pogrebnoi, Lucian Lupascu, Andrei Uncu, Fliur Macaev

Background: The therapeutic options in invasive candidiasis and aspergillosis are limited and don’t provide expected results. Introducing a new drug in the therapeutic practice can improve the quality of life of immunocompromised patients. The aim of this research is to study the antimycotic activity of new substance phenoxithiazolchloralum (MF-0010) on Aspergillus spp., Candida albicans, and Saccharomyces cerevisiae. Material and methods: Phenoxythiazolchoralum has been kindly offered by the Institute of Chemistry. The standards were offered by Nicolae Testemitanu State University of Medicine and Pharmacy. Antifungal activity of the phenoxythiazolchloralum against Aspergillus spp. was evaluated by microdilution method. The successive double dilution method was used for determination of in vitro susceptibility against Candida albicans, and Saccharomyces cerevisiae. Results: For the first time, it was studied in vitro susceptibility of MF-0010 against Aspergillus spp., Candida albicans, Saccharomyces cerevisiae. With at least 0.05 μM/ml difference of MF-0010 MIC value from standards, it can be considered quite more potent than ketoconazole and bifonazole against Aspergillus fumigatus, Aspergillus versicolor, Aspergillus ochramensis. The MIC/MCF ratios of MF-0010 are lower than nistatine ones with 0.08 μMol for both pathogens: Candida albicans, and Saccharomyces cerevisiae. Conclusions: All analyzed pathogens were susceptible to MF-0010. According to experimental data on Aspergillus spp., the antimycotic activity of MF-0010 is quite better than the standards one. The MIC/MCF ratios showed in vitro significant susceptibility of MF-0010 against Candida albicans.

75-79

Authors: Valeriu Cusnir, Lilia Dumbraveanu, Liliana Groppa, Vitalie Cusnir, Nicolae Bobescu, Valeriu Cusnir Jr

Background: Inflammatory glaucoma, also known as uveitic glaucoma is a multifactorial process of inflammation that causes the rising of intraocular pressure (IOP) accompanied by morphological and physiological modifying similar to open angle glaucoma. The mechanisms by which ocular inflammation causes an increase of the IOP are not integrally comprehended, and many of the relevant pathways and features are still covered with a veil of mystery. The eyes of uveitic patients are defined by complex interactions between the angles (open or closed), trabecular outflow, fluctuations in the aqueous production and the response to steroids. Regarding the elevation of IOP in these individuals, it is mostly attributed to the increased outflow resistance, which distorts the equilibrium between aqueous production and outflow. Conclusions: Inflammatory glaucoma is a multifactorial pathology that needs a careful diagnosis and therapeutical approach in order to obtain a good management of inflammatory process and intraocular pressure. There are a lot of pathological pathways that influence the evolution of inflammatory glaucoma and make treatment more difficult. Last years, glaucoma treatment has significantly improved, but to better understand pathogenesis of uveitic glaucoma more scientific studies are necessary.

11-15

Authors: Svetlana Diacova

Background: Prolonged forms of otitis media (OM) lead to chronic hearing loss and disability from childhood. Wide spectrum of therapeutic approaches is used in management of OM in children. Objective evaluation of the middle ear after different curative modalities will help in analysis of treatment feasibility. The objective of this article was to compare the results of middle ear noninvasive monitoring after different surgical procedures in order to select the most effective one in prolonged otitis media forms. Material and methods: Patients represent 150 children with prolonged OM. Analyzed treatment modalities: I – myringotomy, II – classical tympanostomy, III – modified tympanostomy. Middle ear monitoring included otoscopy and audiometry what was repeated 4 times during 2 years, otomicroscopy in 1 and 2 years and impedance audiometry in 2 years after surgery. The quality of life and general health scores were analyzed before surgery and in 1 and 2 years after surgery. Results: Otoscopic and audiometric data showed stable improvement in 32% of children after myringotomy, 90% of children after classical tympanostomy and 97% of children after modified tympanostomy. Impedance audiometry in 2 years after surgery demonstrated complete restoration of middle ear function in 32% of children after myringotomy, in 78% of children after classical tympanostomy, and in 94% of children after modified tympanostomy. Conclusions: Post-surgical noninvasive monitoring demonstrated advantages of tympanostomy and especially in modified version: improvement and stability of middle ear function and low rate of otitis media persistence or recurrence.

22-25

Authors: Pavel Gavriliuc, Mihail Gavriliuc, Stanislav Groppa, Ronen Leker

Background: Pathological changes in the cerebral white matter can be determined both in small vessel disease and in cerebral amyloid angiopathy. The pattern of involvement may be different depending on the etiology and severity of the process. Objective of the study: Determination and analysis of the pattern of cerebral white matter changes in patients with amyloid angiopathy and involvement of the cerebellum. Material and methods: Patients with intracerebral hemorrhages who were examined by magnetic resonance imaging were prospectively analyzed. Patients were diagnosed with cerebral amyloid angiopathy (CAA) according to Boston criteria. Changes in white matter were interpreted using the Fazekas scale and compared for patients with CAA and patients with CAA and cerebellar involvement. Of the 614 patients with intracerebral hemorrhage, 96 were examined by cerebral magnetic resonance imaging. Of these, 41 patients were diagnosed with amyloid angiopathy, 19 patients with possible amyloid angiopathy, 21 patients – probable and 1 case with defined amyloid angiopathy. Results: Cerebellar involvement was determined in 34% (14/41) of cases. Severe changes in white matter (Fazekas 2-3) were seen in patients with cerebellar involvement (12/14; 86% versus 8/27 and 30% p = 0.002). Conclusions: Involvement of the white matter in the pathological process is more significant in patients with amyloid angiopathy and the involvement of the cerebellum, even after adjusting for risk factors. Patients with cerebellar haemorrhage and severe white matter should be screened for amyloid angiopathy.

32-37

Authors: Andrei Uncu

Background: Propylthiohinothiadiazole is a thiadiazole derivative with pronounced antimycobacterial action. Substance is researched in order to develop methods of analysis and standardization, analytical documents regulating quality for use as an active principle in the development of pharmaceutical forms. Material and methods: 3 series of propylthiohinothiadiazole, internal reference standard of 2-(propylthio)-5H-[1,3,4]-thiadiazole[2,3-b]-quinazolin5-one substance with concentration 99.98%, chromatographic system Shimadzu LC-20AD high-pressure liquid chromatography (HPLC) with UV-VIS detector, acetonitrile and dimethylsulfoxide of purity grade “pro HPLC analysis” (Sigma Aldrih and Merck), bidistilled purified water. Results: Linearity is proved for concentrations of 5-30 µg/ml, the linear regression equation is y=36472x-44580, R²=0.9999. The limit of detection is 0.729 µg/ml and the limit of quantification is 2.210 µg/ml. It was established that the method is accurate (mean recovery values at 80%, 100% and 120% concentration levels were close to 100%). The accuracy of the method was expressed by repeatability and intermediate accuracy. The variation of the chromatographic conditions established that the method is robust. For all validation parameters, relative standard deviation was less than 1. Conclusions: The validation results show that the developed HPLC method is simple, fast, accurate and reproducible.

43-50

Authors: Eugeniu Nicolai, Oxana Vislouh, Vladimir Valica, Sergiu Parii, Livia Uncu

Background: The stability of a drug is an important factor in ensuring its quality.The studied combined ear drops have an increased tendency of degradation, which requires an extensive stability study and obtaining data to determine the shelf life and establish the storage conditions. The purpose of the work: Stability studies of ear drops containing ciprofloxacin, dexamethasone, loratadine and volatile basil oil. Material and methods: International Harmonized Guideline ICH Q1A (R2) stability testing methodology; 3 series of ear drops; reference standards for the active substances (Sigma Aldrich, USA); Shimadzu LC-20AD liquid chromatograph with UV-VIS detector; Fungilab Smart R viscometer; pH meter inoLab 7110; solvents, reagents in accordance with the European Pharmacopoeia. Results: Ciprofloxacin is stable in acid medium, degrades in alkaline medium after 3 hours (approximately 10.0%), under oxidation (19.7%) and light action (17.1%). Dexamethasone degrades in acid medium (by 7.7%) and under oxidation (by 19.9%), it is stable in alkaline medium and under the action of light. Loratadine degrades in acid medium (by 3.0%), is stable in alkaline medium, under oxidation and action of light. In real-time storage conditions (25°C±2°C and RH 60%±5%), it was found that the pharmaceutical form did not change its quality parameters for 24 months. Conclusions: The stability studies under stress and in real time conditions allowed us to select the packaging, the optimal storage conditions and to establish the provisional shelf life for the combined auricular pharmaceutical form during 2 years.

58-65

Authors: Marcel Abras, Artiom Surev, Mariuca Vasa-Nicotera, Vitalie Moscalu, Andrei Grib, Ion Popovici, Catalina Beiu

Background: Aortic stenosis (AS) is the most prevalent primary heart valve disease and the third most prevalent cardiovascular disease in the world, having a severe and slowly progressive evolution. The implementation of Transcatheter Aortic Valve Implantation (TAVI) is necessary because the population is constantly ageing, and most elderly people have various comorbidities, which places them among patients with high surgical risk. The aim was to report immediate and 9 months follow-up results of first TAVI implantations in the Republic of Moldova. Material and methods: Three patients with severe symptomatic AS and high surgical risk underwent TAVI implantation using Portico valves. Results: The mean age was 76.7 ± 1.2 years, 2 women and 1 man. The mean Logistic EuroSCORE II was 5.68 ± 0.67%. Procedural success was achieved in all (100%) patients. After the intervention, it was shown that the GP mean decreased by an average of 20.27±1.61 mmHg, the Vmax of the jet through AoV decreased on average by 2.05±0.19 m/s, and they were maintained all over the nine months follow-up period. Quality of life, using the TASQ (Toronto Aortic Stenosis Quality of Life) questionnaire, was improved by 62.3 ± 2.2 points. Conclusions: TAVI, as a new minimally invasive method of treatment for aortic valve stenosis appears to be safe, with a low rate of early and late complications in elderly patients at high surgical risk, with good clinical outcomes at 9 months. Its implementation in the Republic of Moldova is welcome in the conditions of continuously ageing population and the prevalence of associated comorbidities.

70-73

Authors: Victor Vovc

Background: Undoubtedly, the research studies have played both a decisive and edifying role in the emergence and development of Physiology as a separate science. The research and particularly, the experimental studies, were the milestones for the development of physiology as a distinct science and discipline, used in both general and specific biological and medical education. Physiology is an important and permanent source of research and modeling methods of vital processes among the fundamental and preclinical medical and biological sciences, such as pathophysiology and pharmacology. This short essay does not claim to comprehensively describe the development of physiological research studies within Nicolae Testemitanu State University of Medicine and Pharmacy over 75 years since the university foundation. However, this present chronological presentation with elements of analysis provides historical and current data on the researchers and their research papers, while working as collaborators within the Department of Physiology at our university. Conclusions: This historical review brings conclusive evidence upon the research work conducted by the academic staff and their study results, since the foundation of the Department of Physiology, which have greatly reflected the international research trends in the field of physiological sciences. Current physiological research studies, conducted at the Department of Physiology, are aimed at studying the physiological markers and predictors of different diseases, involving cardiovascular and respiratory systems by means of psychophysiology.

12-17

Authors: Veronica Sardari, Valeriana Pantea, Aurelian Gulea, Olga Tagadiuc, Lilia Andronache, Inna Svet, Victor Tapcov, Valentin Gudumac

Background: Thiol-disulfide metabolism is essential for normal function of the organism. Thus the interest of the scientists in this area of research continues to grow. Material and methods: Copper coordination compounds (CCC), derivatives of thiosemicarbaside (CMD-4, CMJ-33, CMT-67), action on thiol-disulfide metabolism in the healthy Ratta albicans kidneys were studied. The animals were divided in 6 groups of 7 rats each. The control group included healthy rats which were injected i/m physiological solution 3 times a week, for 30 days. The rats from groups 2-6 have got 3 times a week, for 30 days, i/m injections of CCC. The activity of following thiol-disulfide metabolism enzymes in the renal supernatant has been measured: glutathion-reductase (GR), glutathion-peroxidase (GPO), glutathion-S-transferase (G-S-T), γ-glutamyl transpeptidase (γ-GTP), glutaredoxin (Grx), as well the amount of the protein SH-groups and of the total glutathione, reduced glutathione (GSH) and oxidized glutathione (GSSG) in renal tissue. Results: The compounds exhibit different actions: CMT-67 in the dose of 0.1 µM/kg influenced the activity of the glutathione metabolism enzymes – activated γ-glutamyl transpeptidase (γ-GTP) and glutaredoxine (Grx) and inhibited glutathione reductase (GR), while CMD-4 in doses of 0.1 µM/kg and 1.0 µM/kg and CMJ-33 in the dose of 1.0 µM/kg significantly diminished the reduced glutathione (GSH) level and increased the amount of the oxidised one (GSSG). Conclusions: Selective action of the copper coordination copounds established by this study opens new possibilities of their usage in the therapy of kidney diseases.

25-30

Authors: Alina Alsatou, Vergil Petrovici, Natalia Corolcova

Background: The umbilical cord forms connecting link between the fetus and placenta through which the fetal blood flows to and from the placenta. Wharton’s jelly is a specialized tissue which acts as supportive and protective structure substituting for the adventitia of the umbilical vessels. The aim of the study was to reveal the clinical and morphological features of the lean umbilical cord for improving its outcomes. Material and methods: The study included 190 patients divided into 2 groups: L1 – 95 patients with UC abnormalities and L0 – 95 with normal UC. Umbilical cord assessment was based on macro- and microscopic examinations. An entire umbilical cord was available from all patients and examined for diameter. Three full thickness sections of the UC were fixed in 10% formalin and stained with hematoxylin and eosin, Van Gieson’s, Alcian blue for histological examination. Results: A study of the association between the absence of Wharton’s jelly and an unfavorable pregnancy outcome was undertaken. The lean umbilical cord results in reduced fetoplacental circulation, thus resulting in intrauterine growth restriction (p<0.0001), fetal distress and hypoxia, which require the neonatal intensive care (p<0.0001). Morphological examination of the umbilical cord revealed changes in Wharton’s hard and fibrous jelly. Conclusions: This study shows the importance of the knowledge of cord diameter. Clinico-morphological examination of the umbilical cord, including the study of the lean forms is of great importance in the diagnosis of the causes of adverse perinatal outcomes of fetuses and newborns in the obstetrical practice. Therefore, our study confirms that all umbilical cords should be submitted for complete examination.

34-39

Authors: Mariana Turcan, Mihail Maniuc

Background: Inflammatory disease of the paranasal sinuses, due to its high incidence in the nosological structure of morbidity, is a constant problem of modern otorhinolaryngology. The purpose of this study was to assess the importance of modern investigative methods for establishing the diagnosis in children with inflammatory rhinosinusitis. Material and methods: The study was conducted on a group of 55 children, aged 4 to 18 years, diagnosed with inflammatory rhinosinusitis, hospitalized during the 2017-2020 years within ENT Department of Emilian Cotaga Republican Clinical Hospital for Children, Chisinau. The retrospective analysis of the data, retrieved from the clinical observation sheets and their attached documents, as well as from inpatient surgical protocols, during the years 2017-2020, was carried out. Results: The applied diagnostic methods were as following: optical endoscopy, rhinomanometry, acoustic rhinometry, mucociliary clearance, computed tomography. Conclusions: The study revealed that computed tomography and optical endoscopy provide an accurate mapping of rhinosinusal structures. Nowadays, inflammatory rhinosinusitis is definitely diagnosed by highly accurate methods, namely the optical endoscopy and computed tomography that are “the gold standard”. The functional tests such as rhinomanometry and acoustic rhinometry are used to assess permeability and endonasal geometry, as well as evaluation of respiratory function in children with rhinosinusitis. The mucociliary nasal clearance plays a major role in modern diagnostic algorithm, being an essential index in assessing the functional status of the nasal mucosa and performing the protective function.

44-48

Authors: Oleksandr Slobodian, Volodymyr Guzak

Background: The value of the study is finding typical and variant anatomy of the palmar arteries during fetal and early neonatal periods of ontogenesis, which is important while performing amputations, osteosynthesis, resection of bones followed by further prosthetics, as well as during catheterization of the arterial branches in order to deliver diagnostic and therapeutic substances in fetuses, neonates and infants. Material and methods: The study was performed on 51 specimens of dead fetuses (from 4 to 10 months) and 10 neonates of both sexes died due to the causes not related to diseases of the muscular-skeletal system and without external signs of anatomical defects, without visual macroscopic deviations or anomalies from the normal structure of the upper limbs. Results: During the perinatal period of ontogenesis the typical anatomy of the palmar arteries (formation of the superficial palm arch) is found in 62% of cases, the variant one – in 38%. The variant structure of the palmar artery during the perinatal period of ontogenesis is divided into closed and openended (continuous superficial palmar arch is absent) arteries. In their turn, closed palmar arteries include anastomosis formation in the form of an arch and without arch formation. In case of open-ended arteries the palm is supplied with blood through the branches from two or three arteries. The older the fetus is, the greater percentage ratio of the typical structure of the palmar artery becomes (9% of cases more) in comparison with other forms. Moreover, the open-ended artery system increases when the palmar surface is supplied with blood from the three arteries (28% of observations more) in comparison with those cases when the palmar surface is supplied through the two arteries. During the perinatal period of ontogenesis the amount of the variant arterial structure is more found on the left palm (25%) compared to the right one (17.5%). Conclusions: Detection of the typical and variant anatomy of the palmar arteries is a morphological precondition to introduce new methods of performing radical and reconstructive-restorative surgeries on the hand.

54-56

Authors: Ana Otgon, Leonid Lisii

Background: Alzheimer’s disease (AD) is a neurodegenerative disease of the elderly, being recognized worldwide as the most common cause of dementia. However, the harm generated by this disease to women and men is disproportionate, in women the disease is recorded twice as much. Numerous research studies have tried to find an answer regarding the causes of this disproportionality. So far, some fundamental differences between macroscopic, microscopic and biochemical structures of female vs. male brain have been investigated. First of all, emphasis was placed on macroscopic structural differences. In this study, a particular role was attributed to APOE4 gene which was shown to be an increased risk factor of AD in women who possess this allele. Hormonal changes in women, such as decreased postmenopausal estrogen, greatly influence disease incidence and prevalence. All these factors tell about the increased susceptibility of women to this disease. However, the definite mechanisms of this disease are incompletely elucidated and further studies are needed. Conclusions: The identification of pathobiochemical mechanisms based on gender, that influence the incidence and prevalence of Alzheimer’s disease is essential. Thus, it could be a target in the development of effective preventive therapeutic strategies from the prodromal phase of the disease. In this context, the development of personalized treatment according to gender specifics should be considered in future.

63-65

Authors: Elena Portnoi

Background: Folliculo-stellate cells were first identified with electron microscopy as a non-hormone secreting accessory cells, star-shaped and follicleforming cells. They represent about 4-20% of pituitary cells from the anterior pituitary lobe. The folliculo-stellate cells control several anterior pituitary activities. However, they do not produce hormones, but they produce growth factors, cytokines, vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), leukemia inhibitory factor (LIF), IL-6, and macrophage migration inhibitory factor (MIF), IL-1β and TNF-α. Regardless of a long period of pituitary research and many morphological, cytophysiological studies, it has been reported that a precise understanding of the major functions of folliculo-stellate in the pituitary gland remains unknown. Consequently, there are still many unsolved issues. Conclusions: This article intends to review the characteristics of folliculo-stellate cells and their uncertain functions in the adenohypophysis, such as their importance as stem cells, in the process of maturation and aging. New researches about the origin and differentiation of folliculo-stellate cells may provide many relevant answers about physiopathology of the pituitary gland and the pathogenesis of pituitary tumors, as well as their influence on the quality of life. Immunohistochemical profile studies of folliculo-stellate cells in pituitary gland, can be useful in elucidation of morphological features and may have a predictive role for the early identification of pituitary microadenomas, prognosis of pituitary tumors and treatment.