Armond Daci

Guillain Barré syndrome (GBS): new insights in the molecular mimicry between C. jejuni and human peripheral nerve (HPN) proteins.

Profile and immunoreactivity of proteins from HPN tissue, and from Campylobacter jejuni (O:19) were investigated. Proteins were extracted, separated by SDS-PAGE, their cross reactivity monitored by Western blotting, and identified by nHPLC-nESI-HRMS analysis. Proteins from C. jejuni, at Mw ~70 KDa were chaperone/co-chaperone proteins (GroEL, DnaK and HtpG). In the corresponding HPN band were serum albumin, neurofilament light peptide, cytoskeletal keratins and one HSP 70 and one HSP60. These chaperones reciprocally share high primary sequence homology and conservation of their known epitopes. These findings suggest that HSP chaperones may be suitable candidates involved in the molecular mimicry triggering GBS.

Polymorphic Variants of SCN1A and EPHX1 Influence Plasma Carbamazepine Concentration, Metabolism and Pharmacoresistance in a Population of Kosovar Albanian Epileptic Patients

Aim The present study aimed to evaluate the effects of gene variants in key genes influencing pharmacokinetic and pharmacodynamic of carbamazepine (CBZ) on the response in patients with epilepsy. Materials & Methods Five SNPs in two candidate genes influencing CBZ transport and metabolism, namely ABCB1 or EPHX1, and CBZ response SCN1A (sodium channel) were genotyped in 145 epileptic patients treated with CBZ as monotherapy and 100 age and sex matched healthy controls. Plasma concentrations of CBZ, carbamazepine-10,11-epoxide (CBZE) and carbamazepine-10,11-trans dihydrodiol (CBZD) were determined by HPLC-UV-DAD and adjusted for CBZ dosage/kg of body weight. Results The presence of the SCN1A IVS5-91G>A variant allele is associated with increased epilepsy susceptibility. Furthermore, carriers of the SCN1A IVS5-91G>A variant or of EPHX1 c.337T>C variant presented significantly lower levels of plasma CBZ compared to carriers of the common alleles (0.71±0.28 vs 1.11±0.69 μg/mL per mg/Kg for SCN1A IVS5-91 AA vs GG and 0.76±0.16 vs 0.94±0.49 μg/mL per mg/Kg for EPHX1 c.337 CC vs TT; P<0.05 for both). Carriers of the EPHX1 c.416A>G showed a reduced microsomal epoxide hydrolase activity as reflected by a significantly decreased ratio of CBZD to CBZ (0.13±0.08 to 0.26±0.17, p<0.05) also of CBZD to CBZE (1.74±1.06 to 3.08±2.90; P<0.05) and CDRCBZD (0.13±0.08 vs 0.24±0.19 μg/mL per mg/Kg; P<0.05). ABCB1 3455C>T SNP and SCN1A 3148A>G variants were not associated with significant changes in CBZ pharmacokinetic. Patients resistant to CBZ treatment showed increased dosage of CBZ (657±285 vs 489±231 mg/day; P<0.001) but also increased plasma levels of CBZ (9.84±4.37 vs 7.41±3.43 μg/mL; P<0.001) compared to patients responsive to CBZ treatment. CBZ resistance was not related to any of the SNPs investigated. Conclusions The SCN1A IVS5-91G>A SNP is associated with susceptibility to epilepsy. SNPs in EPHX1 gene are influencing CBZ metabolism and disposition. CBZ plasma levels are not an indicator of resistance to the therapy.

Individualizing Treatment Approaches for Epileptic Patients with Glucose Transporter Type1 (GLUT-1) Deficiency

Monogenic and polygenic mutations are important contributors in patients suffering from epilepsy, including metabolic epilepsies which are inborn errors of metabolism with a good respond to specific dietetic treatments. Heterozygous variation in solute carrier family 2, facilitated glucose transporter member 1 (SLC2A1) and mutations of the GLUT1/SLC2A2 gene results in the failure of glucose transport, which is related with a glucose type-1 transporter (GLUT1) deficiency syndrome (GLUT1DS). GLUT1 deficiency syndrome is a treatable disorder of glucose transport into the brain caused by a variety of mutations in the SLC2A1 gene which are the cause of different neurological disorders also with different types of epilepsy and related clinical phenotypes. Since patients continue to experience seizures due to a pharmacoresistance, an early clinical diagnosis associated with specific genetic testing in SLC2A1 pathogenic variants in clinical phenotypes could predict pure drug response and might improve safety and efficacy of treatment with the initiation of an alternative energy source including ketogenic or analog diets in such patients providing individualized strategy approaches.

Arctigenin improves vascular tone and decreases inflammation in human saphenous vein

ABSTRACT The goal of this study was to test the effects of bioactive phenylpropanoid dibenzylbutyrolactone lignan arctigenin (ATG) in vascular tone. Human bypass graft vessel, from a saphenous vein (SV), were set up in organ bath system and contracted with potassium chloride (KCl, 40 mM). Two concentration–response curves of noradrenaline (NE) (10 nM–100 &mgr;M) separated with an incubation period of 30 min without (Control) or with ATG (3–100 &mgr;M) were established. Inhibitors of nitric oxide, prostaglandins, K+ related channels or calcium influx were used to delineate the molecular mechanisms beyond ATG effects. To investigate anti‐inflammatory actions, SV were treated with 10 &mgr;M or 100 &mgr;M ATG and incubated for 18 h in the absence or presence of both interleukin‐1beta (IL‐1&bgr;) and lipopolysaccharide (LPS) to mimic the physiological or inflamed tissue conditions. Proatherogenic and inflammatory mediators İnterleukine‐1 beta (IL‐1&bgr;), Monocyte Chemoattractant Proteine‐1 (MCP‐1), Tumor Necrosis Factor‐ &agr; (TNF‐&agr;), İnterleukine‐6 (IL‐6), Prostaglandin E2 (PGE2) and İnterleukine‐8 (IL‐8) in the supernatant were measured. ATG significantly decreased vascular contractile response to NE. Moreover, it reduced contractions induced by KCl and cumulative addition of CaCl2. The mediators were significantly increased in inflammatory conditions compared to normal conditions, an effect which was inhibited by ATG (10 and 100 &mgr;M). ATG reduces contractions in SV and decreases the production of proinflammatory‐proatherogenic mediators, setting the stage for further evaluating the effect of ATG in cardiovascular diseases.

Microperforated Hymen Presenting Spontaneous Pregnancy with Cesarean Delivery and Hymenotomy Surgery: A Case Report

BACKGROUND: Female genital tract anomalies including imperforate hymen affect sexual life and fertility. CASE PRESENTATION: In the present case, we describe a pregnant woman diagnosed with imperforate hymen which never had penetrative vaginal sex. A 27–year-old married patient with 2 months of amenorrhea presented in a clinic without any other complications. Her history of difficult intercourse and prolonged menstrual flow were reported, and subsequent vaginal examination confirmed the diagnosis of imperforate hymen even though she claims to made pinhole surgery in hymen during puberty. Her urine pregnancy test was positive, and an ultrasound examination revealed 8.3 weeks pregnant. The pregnancy was followed up to 39.5 weeks when she entered in cesarean delivery in urgency. Due to perioperative complications in our study, a concomitant hymenotomy was successfully performed. The patient was discharged with the baby, and vaginal anatomy was restored. CONCLUSIONS: This case study suggests that even though as microperforated hymen surgery in puberty can permit pregnancy and intervention with cesarean section and hymenotomy is a good option to reduce the resulting perioperative complications which indirectly affect the increase of the fertilisation and improvement of later sexual life.

Pharmacotherapy Evaluation and Utilization in Coronary Artery Bypass Grafting Patients in Kosovo during the Period 2016-2017

BACKGROUND: Coronary Artery Bypass Grafting (CABG) is realised in patients with critical or advanced disease of coronary arteries. There are different pharmacotherapeutic approaches which are used as management, treatment and preventive therapy in cardiovascular disease or related comorbidities. Performing a successful surgery, pharmacotherapy, and increase of bypass patency rate remains a serious challenge. AIM: This study aims to analyse the patient characteristics undergoing CABG and evaluation of their drug utilisation rate and daily dosages in the perioperative period. MATERIAL AND METHODS: Data were collected from 102 patients in the period 2016-2017 and detailed therapeutic prescription and dosages, patient characteristics were analysed before the operation, after the operation and visit after operation in the Clinic of Cardiac surgery-University Clinical Center of Kosovo. RESULTS: Our findings had shown that patients provided to have normal biochemical parameters in the clinic before the operation, and were related to cardiovascular diseases and comorbidities and risk factors with mainly elective intervention. The, however, higher utilisation of cardiovascular drugs such as beta blockers, diuretics, anticoagulants, statins and lower calcium blockers, ACEi, ARBs, hydrochlorothiazide, amiodarone were founded. ARBs, beta blockers, statins, nitrates and nadroparin utilisation decreased after operation and visit after the operation, whereas amiodarone only in the visit after the operation. Diuretics are increased after the operation which decreases in the visit after the operation. Regarding the daily dosage, only metoprolol was increased in the visit after operation (P < 0.001) and visit after operation (P < 0.05) whereas losartan and furosemide were increased (P < 0.01) and (P < 0.05) respectively. CONCLUSION: The study showed that beta blockers, statins, aspirin, nitrates (before the operation), furosemide and spironolactone are the most utilised drugs. However, we found low utilisation rate for ACEi, ARBs, clopidogrel, nadroparin, warfarin, xanthines, amiodarone, calcium blockers. Daily dosages were different compared to before CABG only in metoprolol, losartan, and furosemide.

Impact of combined non-surgical and surgical periodontal treatment in patients with type 2 diabetes mellitus-a preliminary report randomized clinical study

Background/objectives: Scientific evidence regarding the effects of chronic periodontitis on Type 2 Diabetes Mellitus (T2M) is fragmentary and not definitive. This intervention study was designed to evaluate the effects of a Non-Surgical Procedure (NSP) in addition to a surgical procedure on systemic inflammation and glycaemic control in patients with T2M and periodontitis and Non-Diabetic (ND) patients with periodontitis. Material and Methods: A total of 100 patients with diabetes were randomly allocated to a treatment group and a control group. At least one tooth was extracted from each patient. After extraction, the control group (n=50) did not receive any other treatment until the 3-month follow-up. Patients in the treatment group (n=50) received Full-Mouth Scaling and Root Planing (FM-SRP).The Mean Probing Depth (MPD), Mean Attachment Level (MAL), Plaque Index (PI), Bleeding on Probing (BOP), fasting blood samples for the measurement of high-sensitivity C-Reactive Protein (hs-CRP), and glycated hemoglobin (HbA1c) were measured or taken at baseline and 3 months after treatment. To investigate the effect of diabetes on the therapeutic procedure’s outcome, ND patients with periodontitis (n=60) were divided into two equal groups and subjected to the same procedures and analysis. Results: HbA1c and hs-CRP decreased significantly in the diabetic groups and decreased more markedly when FM-SRP was added to tooth extraction (P<0.001). For ND patients, all of the examined periodontal parameters were in favor of the combination therapy (P<0.001). Conclusion: Non-surgical periodontal treatment can help improve the outcome of surgical periodontal procedures by reducing systemic inflammatory status and improve glucose metabolism.

The impact of bilateral vagotomy on the physostigmine-induced airway constriction in ferrets

Vagal innervations have a great role in the respiratory function and are the main route of signal transmission from respiratory neural centers into the trachea and others conducting airways. We have investigated the role of central mechanisms related to vagal neural pathways and the cholinergic outflow in tracheobronchial smooth muscle tone and lung mechanics parameters. Parameters of lung mechanics such as lung resistance (RL), dynamic compliance (Cdyn) and pressure in bypassed tracheal segment (Ptseg) were measured before and after vagotomy and asphyxia test. Before vagotomy (BV), the control measurements were obtained and physostigmine was administered systemically, in increasing dose 10, 40 and 100μg/kg body weight (bw) with 15min interval between doses. After vagotomy (AV), administration of physostigmine with the same doses as BV has been done and the asphyxia challenge was conducted as per study protocol. The values of Ptseg and RL after physostigmine administration, BV vs. AV, respectively, at maximal dose of 100μg/kg bw were 32.5±3.3cm H2O, and 10.6±1.5cm H2O (p<0.0001); 0.16±0.04cm H2O/mL/s, and 0.067±0.006cm H2O/mL/s AV (P<0.05). The Cydn values were affected after physostigmine administration only at the lowest dose of 10μg/kg bw, and BV was 0.75±0.05mL/cm H2O vs. 0.53±0.04mL/cm H2O AV (P<0.004). Cholinergic outflow produced increases in tracheal tone, lung resistance and a decrease in dynamic compliance before, but not after vagotomy. Our results show the high impact of central neuronal mechanism in parameters of lung mechanics and respiration. This study indicates that vagal nerves have a crucial role, in the transmission of impulses initiated from central nervous system, in regulating the respiration by contraction or relaxation of airway smooth muscle tone.

Analgesics Use in Dentistry

Pain is a protective warning sign activated by tissue damage during different pathological processes. The clinical manifestation of pain is individual, multifactorial and very complex and requires the implementation of sound pharmacological approaches. The treatment of odontogenic pain is focused not only in the relief of pain but also in the suppression of causes of pain, mainly the inflammation. Acting as inhibitors of pain mechanism, analgesics are used for symptomatic treatment of pain. There are several groups of analgesic drugs used in dentistry practice and most frequent are nonsteroidal anti-inflammatory drugs (NSAIDs) and aniline analgesics. The contemporary strategies for the treatment of odontogenic pain are focused in analgesic drug combinations, which are more effective and have a better safety profile. Ibuprofen and acetaminophen agents are considered gold standard of dental analgesia for mild to moderate intensity of pain, while in moderate to severe pain the use of individual opioid analgesics or combination of opioid and nonopioid analgesics is recommended. The treatment of pain in children and elderly patients is associated with some limitations accompanied with safety concerns and dose reduction. Treatment of pain in dentistry is focused in achieving the satisfactory level of analgesia at low doses possible.

Antibiotic utilisation in adult and children patients in Kosovo hospitals

Objectives There are no reliable data on antibiotic use in Kosovo hospitals. The aim of this survey was to monitor volumes and patterns of antibiotic use in hospitalised patients in order to identify targets for quality improvement. Methods Data on antimicrobial use were collected from seven hospitals in Kosovo during 2013 using the standardised point prevalence survey (PPS) methodology as developed by the ESAC (European Surveillance of Antimicrobial Consumption) and ARPEC (Antibiotic Resistance and Prescribing in European Children). The survey included all inpatients receiving an antimicrobial agent on the day of the PPS. Results Overall, 1667 patients were included in the study: adults 1345 (81%) and children 322 (19%). Of the hospital inpatients, 579/1345 (43%) adults and 188/322 (58%) children received at least one antibiotic during a hospital stay. The top three antibacterial subgroups (ATC level 3) were β-lactam antibiotics, cephalosporins and aminoglycosides. In all hospital centres, the most commonly prescribed antibiotic was ceftriaxone (39% for adult and 36% for children). Antibiotics were administered mainly parenterally in 74% of adults and 94% of children. Empirical prescribing was higher in adults 498/579 (86%) and children 181/188 (96%), compared with targeted treatment based on susceptibility testing—81 (14%) and 8 (4%), respectively. Conclusions Antibiotic use in Kosovo’s hospitals is very high. Gathered data will be an important tool to identify targets for quality improvement and will support preparation of guidelines and protocols for the prudent use of antibiotics.