Metformin in Glaucoma Treatment.

PRCIS: Rigorous trials are essential to develop comprehensive treatment strategies that fully exploit the therapeutic potential of metformin in the treatment of glaucoma. OBJECTIVE: The objective of this study was to evaluate the potentially beneficial effect of metformin on glaucoma risk factors and to investigate the underlying mechanisms. The aim is to contribute to the development of new treatment strategies for glaucoma. METHODS: We searched for studies that assessed the effects of metformin on glaucoma risk factors and the associated underlying mechanisms. Our search included electronic databases such as PUBMED, EMBASE, and clinicaltrials.gov. RESULTS: Unfortunately, we did not find any clinical trials that specifically investigated the impact of metformin on glaucoma. However, data from experimental studies demonstrated the capability of metformin to modulate various pathways that could contribute to neuroprotection in glaucoma. CONCLUSION: In order to develop comprehensive treatment strategies that fully exploit the therapeutic potential of metformin in the treatment of glaucoma, rigorous trials are essential. These studies are necessary to demonstrate both the safety and efficacy of metformin in the context of glaucoma treatment.

Exploring the Relationship between Anti-VEGF Therapy and Glaucoma: Implications for Management Strategies.

A short-term increase in intraocular pressure (IOP) is a common side effect after intravitreal anti-VEGF therapy, but a sustained increase in IOP with the development of secondary glaucoma has also been reported in some studies after repeated intravitreal anti-VEGF injections. The aim of this review is to present and discuss the possible pathophysiological mechanisms and factors contributing to a sustained rise in IOP, as well as treatment strategies for patients at risk. Close monitoring and adjustable IOP-lowering treatment are recommended for high-risk patients, including those with glaucoma, angle-closure anomalies, ocular hypertension or family history of glaucoma; patients receiving a high number of injections or at shorter intervals; and patients with capsulotomy. Strategies are needed to identify patients at risk in a timely manner and to prevent sustained elevation of IOP.

Correlation between level of vitamin D in serum and value of lung function in children diagnosed with bronchial asthma.

INTRODUCTION: Many authors in their research have suggested an association between vitamin D and asthma, but the results from these publications are sometimes confusing. AIM: Our aim was to assess the relationship between serum vitamin D and lung function in patients previously diagnosed with asthma. MATERIALS AND METHODS: The present study started in September 2019 and was completed in May 2020. All patients were diagnosed at the University Clinical Center-Prishtina, Kosovo. Spirometry was performed on children of ages 6-16 years old with a spirometer according to the recommendations of the American Thoracic Society. RESULTS: Of the 57 children who visited the University Clinical Center of Kosovo-Department of Pediatrics, 29 were diagnosed with asthma. The Spearman coefficient correlation showed statistical significance between vitamin D and body weight, and vitamin D and FEF75% at level 0.05. Other parameters did not show statistical significance with vitamin D, but such statistical significance was found in other parameters between asthma and healthy groups. CONCLUSIONS: Our data suggested that serum vitamin D level was insignificant for FVC%, FEV1%, Tiffeneau Index values, and PEF. Statistical significance was observed between vitamin D and body weight; vitamin D and FEF75% (p=0.05).

Home-Based Perimetry for Glaucoma: Where Are We Now?

PURPOSE: To systematically summarize the current literature on home-based perimeters for glaucoma. METHODS: A systematic review was conducted in accordance with the PRISMA-DTA checklist. Studies reporting portable perimeters designed for home use were retrieved from electronic databases and handsearching of reference lists of relevant publications. Studies reporting diagnostic accuracy data were evaluated with the QUADAS-2 tool and using standard automated perimetry as the reference standard. Other aspects of the technology such as detection of disease progression and patient acceptability were also included. Data were reported in a narrative and tabular format. RESULTS: Of 18 included studies, 10 evaluated tablet-based perimeters, 4 evaluated web-based perimeters, and 4 evaluated head-mounted displays. Most studies used a clinic or laboratory setting. All studies reporting diagnostic accuracy data had high risk of bias in at least one domain. Across studies, sensitivity ranged from 54% in detecting mild to 91% in detecting moderate/severe glaucoma patients from controls, while specificity was between 50% and 100% for any form of glaucoma. The reported acceptability was high but had high risk of bias. CONCLUSION: Several promising technologies designed for home-based perimetry have been reported. Current studies used a controlled setting in highly selected populations. There is uncertainty on the performance and value of home-based perimetry for glaucoma. Additional efforts are required to elucidate the ability of the home-based perimeters to detect glaucoma and disease progression in real life situations.

Rivaroxaban improves vascular response in LPS-induced acute inflammation in experimental models.

Rivaroxaban (RVX) was suggested to possess anti-inflammatory and vascular tone modulatory effects. The goal of this study was to investigate whether RVX impacts lipopolysaccharide (LPS)-induced acute vascular inflammatory response. Male rats were treated with 5 mg/kg RVX (oral gavage) followed by 10 mg/kg LPS i.p injection. Circulating levels of IL-6, MCP-1, VCAM-1, and ICAM-1 were measured in plasma 6 and 24 hours after LPS injection, while isolated aorta was used for gene expression analysis, immunohistochemistry, and vascular tone evaluation. RVX pre-treatment significantly reduced LPS mediated increase after 6h and 24h for IL-6 (4.4±2.2 and 2.8±1.7 fold), MCP-1 (1.4±1.5 and 1.3±1.4 fold) VCAM-1 (1.8±2.0 and 1.7±2.1 fold). A similar trend was observed in the aorta for iNOS (5.5±3.3 and 3.3±1.9 folds reduction, P<0.01 and P<0.001, respectively), VCAM-1 (1.3±1.2 and 1.4±1.3 fold reduction, P<0.05), and MCP-1 (3.9±2.2 and 1.9±1.6 fold reduction, P<0.01). Moreover, RVX pre-treatment, improved LPS-induced PE contractile dysfunction in aortic rings (Control vs LPS, Emax reduction = 35.4 and 31.19%, P<0.001; Control vs LPS+RVX, Emax reduction = 10.83 and 11.48%, P>0.05, respectively), resulting in 24.5% and 19.7% change in maximal constriction in LPS and LPS+RVX respectively. These data indicate that RVX pre-treatment attenuates LPS-induced acute vascular inflammation and contractile dysfunction.

Tuberculosis drug safety and pharmacovigilance in health system of Kosova: A cross-sectional analysis.

BACKGROUND: Tuberculosis (TB) remains a significant worldwide social and life-threatening epidemiological problem. Because this disease requires multiple drug treatment and prolonged therapy for several months, followed by a high probability of adverse effects (AEs), we assessed AE monitoring for anti-TB drugs in the Health Care System of Kosova. METHODS: This survey was a cross-sectional analysis performed at the primary, secondary and tertiary health care levels in Kosova. We included 930 registered tuberculosis patients within three levels of this health system in our study. Furthermore, we interviewed 62 physicians and 71 nurses at TB health facilities. Data were collected from official TB registers and personal contact with patients for 12 months. RESULTS: The representative age group was 19 to 29 years (30.49%), followed by a group of patients aged >60 years (23.23%). Among 930 patients treated with TB drugs, the total incidence of adverse AEs was 29.03%. Female TB patients had a higher rate of AEs than did male patients (33.56% vs 28.84%, respectively). The highest incidence of registered AEs was recorded in the gastrointestinal system (270, 80.83%), followed by the central nervous system (CNS, 7.50%) and was lower in other organ systems. The reporting of anti-TB drug effects by medical staff (TB medical doctor and TB medical nurse) at different levels of TB medical settings occurred among 62.90% of medical doctors and 81.69% of nurses. Only 53.23% of medical doctors and 46.48% of nurses completed pharmacovigilance training. CONCLUSION: The pharmacovigilance approach in Health System of Kosova is not comprehensible and not systematic. The relatively low incidence of AEs among TB patients is due under reporting of these by medical staff. The knowledge, attitudes, and adherence of medical staff reveal low awareness for pharmacovigilance activities, and this concern should be addressed to reinforce this important issue for the safe treatment of TB patients.

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 ß-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.

Correlation of Procalcitonin and C-Reactive Protein with Intra-Abdominal Hypertension in Intra-Abdominal Infections: Their Predictive Role in the Progress of the Disease.

AIM: To analyse the correlation of procalcitonin (PCT) and C-reactive protein (CRP) values with increased intra-abdominal pressure and to evaluate their predictive role in the progression of Intra-abdominal infections. MATERIALS AND METHODS: A non-randomized prospective study conducted in the group of 80 patients. We have measured the PCT, CRP and intra-abdominal pressure (IAP). RESULTS: According to IAH grades (G), there was a significant difference of PCT values: G I 3.6 ± 5.1 ng/ml, G II 10.9 ± 22.6 ng/ml, G III 15.2 ± 30.2 ng/ml (p = 0.045) until: CRP values were increased in all IAH groups but without distinction between the groups: GI 183 ± 64.5, GII 196 ± 90.2, GIII 224 ± 96.3 (p = 0.17). According to the severity of the infection, we yielded increased values of PCT, IAP and CRP in septic shock, severe sepsis and SIRS/sepsis resulting in significant differences of PCT and IAP. CONCLUSION: Based on the results of our research, we conclude that the correlation of PCT values with IAH grades is quite significant while the CRP results remain high in IAH but without significant difference between the different grades of IAH.

Tuberculosis Treatment Adherence of Patients in Kosovo.

SETTING: The poor patient adherence in tuberculosis (TB) treatment is considered to be one of the most serious challenges which reflect the decrease of treatment success and emerging of the Multidrug Resistance-TB (MDR-TB). To our knowledge, the data about patients' adherence to anti-TB treatment in our country are missing. OBJECTIVE: This study was aimed to investigate the anti-TB treatment adherence rate and to identify factors related to eventual nonadherence among Kosovo TB patients. DESIGN: This study was conducted during 12 months, and the survey was a descriptive study using the standardized questionnaires with total 324 patients. RESULTS: The overall nonadherence for TB patient cohort was 14.5%, 95% CI (0.109-0.188). Age and place of residence are shown to have an effect on treatment adherence. Moreover, the knowledge of the treatment prognosis, daily dosage, side effects, and length of treatment also play a role. This was also reflected in knowledge regarding compliance with regular administration of TB drugs, satisfaction with the treatment, interruption of TB therapy, and the professional monitoring in the administration of TB drugs. CONCLUSION: The level of nonadherence TB treatment in Kosovar patients is not satisfying, and more health care worker's commitments need to be addressed for improvement.

Arctigenin improves vascular tone and decreases inflammation in human saphenous vein.

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, 40mM). Two concentration-response curves of noradrenaline (NE) (10nM-100µM) separated with an incubation period of 30min without (Control) or with ATG (3-100µM) 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 10µM or 100µM ATG and incubated for 18h in the absence or presence of both interleukin-1beta (IL-1ß) and lipopolysaccharide (LPS) to mimic the physiological or inflamed tissue conditions. Proatherogenic and inflammatory mediators Interleukine-1 beta (IL-1ß), Monocyte Chemoattractant Proteine-1 (MCP-1), Tumor Necrosis Factor- α (TNF-α), Interleukine-6 (IL-6), Prostaglandin E2 (PGE2) and Interleukine-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 100µM). 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.

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.

The Predictive Role of Procalcitonin On the Treatment of Intra-Abdominal Infections.

AIM: This study aims to evaluate the algorithm of procalcitonin (PCT) and its role on the duration of antibiotics prescription for intra-abdominal infections. MATERIALS AND METHODS: This study is a prospective controlled study that is conducted in groups of 50 hospitalised patients and 50 controlled group patients. RESULTS: The results indicated that the average duration of antibiotic delivery to the PCT group was -10.6 days (SD ± 6.6 days), while in the control group -13.2 days (SD ± 4.2 days). These data showed a significant difference in the duration of antibiotic therapy and the monitoring role of PCTs in the prediction success of antibiotic treatment. The antibiotic delivery was longer in the septic shock 17 (SD ± 11.7) that corresponds to high PCT values of 67.8 (SD ± 50.9). Recurrence of the infection after the cessation of antibiotics occurred in 2 cases (4%) in the standard group, while it occurred in 3 cases (6%) in the control group. CONCLUSION: The treatment of the intra-abdominal infections based on the PCT algorithm shortens the duration of antibiotic treatment and does not pose a risk for the recurrence of the infection.

Biomechanical and Macroscopic Evaluations of the Effects of 5-Fluorouracil on Partially Divided Flexor Tendon Injuries in Rabbits.

BACKGROUND: The main goals of flexor tendon surgery are to restore digital motion by providing tendon healing and to preserve tendon gliding. Our purpose was to investigate the effects of 5-fluorouracil (5-FU) on tendon adhesions in partially divided profundus flexor tendons (flexor digitorum profundus [FDPs]) following surgical repair and in partially divided FDPs without surgical repair, and to compare the results of the repair versus the nonrepair of zone two injuries via macroscopic and biomechanical evaluations of tendon adhesions. METHODS: We used 32 adult male European rabbits (Oryctolagus cunniculus) weighing from 2.5 to 3.5 kg. The study was performed on the deep flexor tendons of the second and third digits of the right hind paws of the rabbits; thus, a total of 64 tendons were examined in this study. RESULTS: Based on the results achieved in our experimental study, the load (N) significantly increased in subgroup 1a in which the tendons were surgically repaired and were not treated with 5-FU compared with subgroup 2a in which tendons were surgically repaired and treated with 5-FU. CONCLUSIONS: The load (N) significantly increased in subgroup 1a in which the tendons were surgically repaired and were not treated with 5-FU compared to subgroup 2a in which the tendons were surgically repaired and treated with 5-FU. Therefore, these results revealed a decrease in adhesion formation in the subgroup that was treated with 5-FU due to increased resistance to tendon adhesions during their excursion through the tendon sheath, which in this case required greater traction force.

Electrophysiological and functional evaluation of peroneal nerve regeneration in rabbit following topical hyaluronic acid or tacrolimus application after nerve repair.

AIMS AND OBJECTIVES: To investigate and compare the effects of hyaluronic acid (HA), tacrolimus (FK-506) and saline on peripheral nerve regeneration in vivo after topical application at the site of nerve repair. MATERIALS AND METHODS: In the present study, 48 adult male European rabbits (Oryctolagus cuniculus), ranging in weight from 2.5 to 3 kg, were randomly assigned to three experimental groups: Group I (saline), Group II (HA) and Group III (FK-506). After transection and immediate repair of the right sciatic nerve of each rabbit, the nerve repair sites were wrapped with an absorbable gelatin sponge soaked that contained saline, HA and FK-506 in Groups I, II and III, respectively. The left hind leg was used as a control. To evaluate the effects of HA and FK-506 on nerve regeneration, electrophysiological measurements were acquired at 6 and 12 weeks after nerve repair and toe-spreading index (TSI) experiments were conducted at 4, 8 and 12 weeks after nerve repair. RESULTS: Motor nerve conduction velocity (MNCV) was improved in Groups II and III compared to Group I, but no differences between Groups II and III were observed. After 12 weeks, however, the MNCV in Groups I, II and III was 40.04%, 51.16% and 50.42%, respectively, of that in the control group (100%). In addition, at 12 weeks, Grade 4 TSI scores were observed in Groups II and III. CONCLUSION: Electrophysiological analyses and functional evaluations based on the TSI indicate that HA and FK-506 exert similar, positive effects on nerve regeneration that are superior to those observed in response to saline treatment.

Carbamazepine and lamotrigine plasma concentrations in epileptic patients during optimising therapy.

Therapeutic monitoring of antiepileptic drugs is important in process of optimisation of therapy of epileptic patients. Carbamazepine (CBZ) and Lamotrigine (LMT) are important drugs in therapy of epileptic patients which requires the monitoring of concentration of these drugs in serum. Ourstudy aim was the comparison and interpretation of the results of routine therapeutic monitoring of Carbamazepine and Lamotrigine in spotlight of antiepileptic therapy optimisation. We have analyzed 74 blood samples of epileptic patients who were in therapy with Carbamazepine or Lamotrigine. High pressure liquid chromatographywas used in determiningthe serum concentration of above mentioned drugs. Results of our study show the positive correlation between dosage and serum concentration of CBZ. (r = 0.78). The correlation coefficient between the dosage and serum concentration of LMT is higher than CBZ (r = 0.825). In the process of monitoring of serum concentration of CBZ, very important issue is the serum concentration of active metabolite named to carbamazepine-10,11-epoxide (CBZE). The correlation coefficient between the CBZ and its active metabolite was r = 0.57. During analysis of correlation between blood sampling time from last dose intake and serum concentration of respective drug in both drugs (CBZ and LMT) we have found the negative small correlation (r = -0.256 and r = -0.288). The results of our study contribute to other studies which confirm the complexity of therapeutic drug monitoring (TDM) process in general and particularly for CBZ and LMT. The process of TDM requires the selection of adequate analytical method and right appropriate interpretation of the serum concentration of these drugs.

Catecholaminergic microcircuitry controlling the output of airway-related vagal preganglionic neurons.

In this study, we have investigated the ultrastructure and function of the catecholaminergic circuitry modulating the output of airway-related vagal preganglionic neurons (AVPNs) in ferrets. Immunoelectron microscopy was employed to characterize the nature of catecholaminergic innervation of AVPN at the ultrastructural level. In addition, immunofluorescence was used to examine the expression of the alpha(2A)-adrenergic receptor (alpha(2A)-AR) on AVPNs, and norepinephrine release within the rostral nucleus ambiguous (rNA) was measured by using microdialysis. Physiological experiments were performed to determine the effects of stimulation of the noradrenergic locus coeruleus (LC) cell group on airway smooth muscle tone. The results showed that 1) catecholaminergic nerve endings terminate in the vicinity of identified AVPNs but very rarely form axosomatic or axodendritic synapses with the AVPNs that innervate the extrathoracic trachea; 2) AVPNs express the alpha(2A)-AR; 3) LC stimulation-induced norepinephrine release within the rNA region was associated with airway smooth muscle relaxation; and 4) blockade of alpha(2A)-AR on AVPNs diminished the inhibitory effects of LC stimulation on airway smooth muscle tone. It is concluded that a noradrenergic circuit originating within the LC is involved in the regulation of AVPN activity within the rNA, and stimulation of the LC dilates the airways by the release of norepinephrine and activation of alpha(2A)-AR expressed by AVPNs, mainly via volume transmission.