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Dvostruka (pregrađena) desna klijetka - prikriveni pratitelj ventrikularnoga septalnog defekta [Double chambered right ventricle – concealed companion of ventricular septal defect]
Get PDFOBJECTIVE: The primary objective is to present the diagnostic and treatment experiences with double chambered
right ventricle (DChRV ) as a possible consequence of the ventricular septal defect (VSD). ----- RESULTS:The intracavitary
gradient as a consequence of the remodeling with aberrant muscle bundles in the right ventricle was diagnosed in
five children (four females) at the age of 2.3–11.3 years (mean age 6.3 years). All patients had VSD with hemodynamically
nonsignificant L-R shunts (Qp/Qs 10–31%). In three children DChRV developed with primary VSD, in one
with a residual defect after patch repair of perimembranous VSD, and in one four years after adequate VSD closure.
Intracavitary gradient measured by an end-hole catheter was 50–90 mmHg. Two patients had no cardiac symptoms,
while three of them had exercise intolerance.In two patients VSD was located proximally to the obstructive band (perimembranous)
and in two patients distally (subaortic-supracristal, conal-doubly committed). One patient had two VSDs
– one located proximally and one distally to the obstructive band. The defect was so far surgically corrected in three
patients with VSD patch and resection of the obstructive aberrant muscle tissue at the age ranging from two years and
seven months to the age of six years and three months. One patient waits for the same surgical procedure, and the other
one for an isolated aberrant band resection. There were no postoperative complications, no postoperative symptoms
were reported, and maximal intracavitary gradient was 20 mmHg. -----CONCLUSION: Remodeling of RV (DChRV ) is probably
caused by the presence of VSD, independent of its size and location; it can develop in primary, residual VSD, as well as after successful VSD closure. Therefore, patients with VSD, especially with perimembranous and doubly committed
VSD need a continuous follow up even after operation. Long-term follow up is necessary due to possible obstruction
recurrence, subaortic membrane and/or aortic valve insufficiency appearance. Surgical removal of the hypertrophic
and aberrant tissue is an adequate way of treatment with relatively rare serious complications. Regarding the
expected progressive course of the disease, the operative treatment in significant DChRV obstruction even in the absence
of symptoms is justified
100 godina nakon prve splenektomije u imunosnoj trombocitopeniji - je li laparoskopska splenektomija još i danas dobra terapijska metoda? Prikaz vlastitih iskustava [A hundred years after first splenectomy for immune thrombocytopenia, is laparoscopic splenectomy still valid as a treatment option? A single center experience]
Get PDFAIM: A single center experience with laparoscopic splenectomy (LS) in the treatmen t of immune thrombocytopenia
(ITP) is presented in this paper. In addition, we discuss the role of splenectomy in the era of thrombopoietin
receptor agonists (TPO-RAs). ----- PATIENTS AND METHODS: In this retrospective study, we present our 35 patients who underwent
LS in the period of 12 years. There were 26 women and nine men with a median age of 50 years (ranging from 19
to 85 years). Prior to LS, all patients were treated with glucocorticoids +/- intravenous immunoglobulins (IVIG),
whereas seven patients received also rituximab. The median time to splenectomy was seven months (ranging from one
to 103 months). ----- RESULTS: Four (11%) patients failed to reach response after LS, and additional six patients relapsed during
the follow up. After a median follow up of 33 months, the remaining 25 (71%) patients required no further treatment.
The estimated sustained response rate at fi ve years was 59%. Patients who underwent splenectomy in the fi rst year after
the diagnosis had better outcome when compared to patients with delayed splenectomy (P= 0.048). Sex and age did not
infl uence the treatment outcome. Four patients had early serious postoperative complications of LS: portal vein thrombosis, deep vein thrombosis of the leg, sepsis, and intraperitoneal bleeding that required surgical revision. There were
no deaths, nor late serious infections. Ten (29%) patients reported fatigue after LS. ----- CONCLUSION: Long-term cure rate
of about 60% is comparable to other studies. However, we observed better response in patients who underwent splenectomy
earlier. In our opinion, LS may still be considered as a safe, successful, and cost-effective second-line treatment
of ITP, especially in patients who are in favor of fast and highly curative treatment. Nevertheless, the introduction of
TPO-RAs will inevitably decrease the role of LS in Croatia, as in the western world
The interactions of p53 with tau and Aß as potential therapeutic targets for Alzheimer’s disease
Get PDFAlzheimer's disease (AD), the most common progressive neurodegenerative disorder, is characterized by severe cognitive decline and personality changes as a result of synaptic and neuronal loss. The defining clinicopathological hallmarks of the disease are deposits of amyloid precursor protein (APP)-derived amyloid-β peptides (Aβ) in the brain parenchyma, and intracellular aggregates of truncated and hyperphosphorylated tau protein in neurofibrillary tangles (NFT). At the cellular and molecular levels, many intertwined pathological mechanisms that relate Aβ and tau pathology with a transcription factor p53 have been revealed. p53 is activated in response to various stressors that threaten genomic stability. Depending on damage severity, it promotes neuronal death or survival, predominantly via transcription-dependent mechanisms that affect expression of apoptosis-related target genes. Levels of p53 are enhanced in the AD brain and maintain sustained tau hyperphosphorylation, whereas intracellular Aβ directly contributes to p53 pool and promotes downstream p53 effects. The review summarizes the role of p53 in neuronal function, discusses the interactions of p53, tau, and Aβ in the normal brain and during the progression of AD pathology, and considers the impact of the most prominent hereditary risk factors of AD on p53/tau/Aβ interactions. A better understanding of this intricate interplay would provide deeper insight into AD pathology and might offer some novel therapeutic targets for the improvement of treatment options. In this regard, drugs and natural compounds targeting the p53 pathway are of growing interest in neuroprotection as they may represent promising therapeutic approaches in the prevention of oxidative stress-dependent pathological processes underlying AD
Uloga pro-angiogenih citokina i njihovih receptora u neovaskularizaciji presađene rožnice [The role of pro-angiogenic cytokines and its receptors in development of corneal neovascularization after penetrating keratoplasty]
Get PDFPURPOSE: To evaluate correlation of vascular endothelial growth factor (VEGF) and its soluble receptors quantity in the recipient cornea at the time of penetrating keratoplasty (PK) and its potential influence on graft rejection.
METHODS: Study included 60 eyes scheduled for PK, equally distributed (n=20) by corneal pathology into 3 risks groups: low, medium, high and controls. Quantity of VEGF-A and C, sVEGFR-1, R2 and R3 was analysed in total cornea and its
layers using an enzyme-linked immunosorbent assay; correlated and compared with neovascularization rate and frequency of graft reaction/rejection in 2 postoperative years.
RESULTS: Highest concentrations of VEGF-A and C in total cornea were in high
risk cases (599 pg/ml; 8.49 ng/ml) and the lowest in controls (102 pg/ml; 5.23ng/ml). Soluble VEGFR-1 and sVEGFR-3 were significantly higher in low risk patients (2.11 ng/ml; 1.62 ng/ml) as compared to high risk group in total cornea (1.8 ng/ml; 0.63 ng/ ml). There were 2 graft rejections, both in high risk group. Eyes with graft reaction had significantly higher VEGF-A (477 pg/ml) and VEGF-C (6.06 ng/ml) and lower sVEGFR-1 (2.23 ng/ml) and R3 (0.49 ng/ml) as compared to clear grafts. Statistical analysis was done by Kruskal-Wallis ANOVA non-parametric test and difference between groups was analysed by Mann-Whitney U-test.
CONCLUSION: Our data implicate that graft reaction occurs more often in corneas with increased VEGF-A and C and decreased soluble forms of their receptors.
Novelty is that soluble VEGF receptors in human corneas may suppress rejection acting as a VEGF sink; thus potentially also serve as anti-rejection therapy
Analiza refleksa treptaja u oboljelih od multiple skleroze [Analysis of the blink reflex in multiple sclerosis patients]
Get PDFMultiple sclerosis (MS) is a chronic autoimmune disease of the central nervous system
characterised by inflammation, demyelinisation and axonal degeneration. Neurophysiological
methods are indispensable part of diagnostic algorithm in MS. The aim of this study was to
examine the electrophysiological characteristics of the blink reflex (BR), compare them with
the brainstem auditory evoked potentials (BAEP) and correlate with MRI findings. The study
included 60 subjects with a clinically definitive MS divided into 2 subgroups: 19 subjects
with symptoms of brainstem damage (MD subgroup) and 41 subjects without signs of
brainstem damage (nonMD subgroup). As a control group 60 age and gender matched healthy
subjects were included. Analysis of BR and BAEP was done on all participants. Data of MRI
findings, regarding presence of demyelinating lesion in brainstem were analyzed in MD and
nonMD subgroup. We analized latencies of R1, R2 and R2' of BR and IPL III-V of BAEP.
The results showed statistically significant difference in the values of all components of BR
measured in the MD and nonMD group compared to the control group as well as MD
compared to nonMD group. The values of IPL III-V did not differ in either MD or nonMD
group compared to the control group. Statistically significant difference was found in
correlation of R1 component and MRI finding in both MS groups. Difference in IPL III-V
latencies noted between MD and nonMD group was not statistically significant. BR analysis
has been shown to be a more sensitive neurophysiological method in patients with MS than
BAEP, regardless of the presence of brainstem damage
Different behaviour of DVL1, DVL2, DVL3 in astrocytoma malignancy grades and their association to TCF1 and LEF1 upregulation
Get PDFKey regulators of the Wnt signalling, DVL1, DVL2 and DVL3, in astrocytomas of different malignancy grades were investigated. Markers for DVL1, DVL2 and DVL3 were used to detect microsatellite instability (MSI) and gross deletions (LOH), while immunohistochemistry and immunoreactivity score were used to determine the signal strengths of the three DVL proteins and transcription factors of the pathway, TCF1 and LEF1. Our findings demonstrated that MSI at all three DVL loci was constantly found across tumour grades with the highest number in grade II (P = 0.008). Collectively, LOHs were more frequent in high-grade tumours than in low grade ones. LOHs of DVL3 gene were significantly associated with grade IV tumours (P = 0.007). The results on protein expressions indicated that high-grade tumours expressed less DVL1 protein as compared with low grade ones. A significant negative correlation was established between DVL1 expression and malignancy grades (P < 0.001). The expression of DVL2 protein was found similar across grades, while DVL3 expression significantly increased with malignancy grades (P < 0.001). The signal strengths of expressed DVL1 and DVL3 were negatively correlated (P = 0.002). However, TCF1 and LEF1 were both significantly upregulated and increasing with astrocytoma grades (P = 0.001). A positive correlation was established between DVL3 and both TCF1 (P = 0.020) and LEF1 (P = 0.006) suggesting their joint involvement in malignant progression. Our findings suggest that DVL1 and DVL2 may be involved during early stages of the disease, while DVL3 may have a role in later phases and together with TCF1 and LEF1 promotes the activation of Wnt signalling
Bypassing major venous occlusion and duodenal lesions in rats, and therapy with the stable gastric pentadecapeptide BPC 157, L-NAME and L-arginine
Get PDFAIM:
To investigate whether duodenal lesions induced by major venous occlusions can be attenuated by BPC 157 regardless nitric oxide (NO) system involvement. -----
METHODS:
Male Wistar rats underwent superior anterior pancreaticoduodenal vein (SAPDV)-ligation and were treated with a bath at the ligated SAPDV site (BPC 157 10 μg, 10 ng/kg per 1 mL bath/rat; L-NAME 5 mg/kg per 1 mL bath/rat; L-arginine 100 mg/kg per 1 mL bath/rat, alone and/or together; or BPC 157 10 μg/kg instilled into the rat stomach, at 1 min ligation-time). We recorded the vessel presentation (filled/appearance or emptied/disappearance) between the 5 arcade vessels arising from the SAPDV on the ventral duodenum side, the inferior anterior pancreaticoduodenal vein (IAPDV) and superior mesenteric vein (SMV) as bypassing vascular pathway to document the duodenal lesions presentation; increased NO- and oxidative stress [malondialdehyde (MDA)]-levels in duodenum. -----
RESULTS:
Unlike the severe course in the SAPDV-ligated controls, after BPC 157 application, the rats exhibited strong attenuation of the mucosal lesions and serosal congestion, improved vessel presentation, increased interconnections, increased branching by more than 60% from the initial value, the IAPDV and SMV were not congested. Interestingly, after 5 min and 30 min of L-NAME and L-arginine treatment alone, decreased mucosal and serosal duodenal lesions were observed; their effect was worsened at 24 h, and no effect on the collateral vessels and branching was seen. Together, L-NAME+L-arginine antagonized each other's response, and thus, there was an NO-related effect. With BPC 157, all SAPDV-ligated rats receiving L-NAME and/or L-arginine appeared similar to the rats treated with BPC 157 alone. Also, BPC 157 in SAPDV-ligated rats normalized levels of NO and MDA, two oxidative stress markers, in duodenal tissues. -----
CONCLUSION:
BPC 157, rapidly bypassing occlusion, rescued the original duodenal flow through IAPDV to SMV flow, an effect related to the NO system and reduction of free radical formation
Haplotypic and genotypic Association of catechol-O-methyltransferase rs4680 and rs4818 polymorphisms and treatment resistance in schizophrenia
Get PDFTreatment-resistant schizophrenia (TRS) continues to be a challenge. It was related to
different factors, including alterations in the activity of brain dopaminergic system, which
could be influenced by the dopamine-degrading enzyme, catechol-O-methyltransferase
(COMT). Variants of the COMT gene have been extensively studied as risk factors
for schizophrenia; however, their association with TRS has been poorly investigated.
The aim of the present study was to determine the haplotypic and genotypic
association of COMT rs4680 and rs4818 polymorphisms with the presence of TRS.
Overall, 931 Caucasian patients diagnosed with schizophrenia (386 females and 545
males) were included, while 270 participants met the criteria for TRS. In males, no
significant haplotypic and genotypic associations between COMT rs4680 and rs4818
polymorphisms and TRS were detected. However, genotypic analyses demonstrated
higher frequency of COMT rs4680 AA genotype carriers compared to G-allele carriers
(p = 0.033) and higher frequency of COMT rs4818 CC genotype carriers than G-allele
carriers (p = 0.014) in females with TRS. Haplotype analyses confirmed that the
presence of the G allele in females was associated with lower risk of TRS. In women with
TRS, the high activity G-G/G-G haplotype was rare, while carriers of other haplotypes
were overrepresented (p = 0.009). Such associations of COMT rs4680 and rs4818 high activity
(G variants), as well as G-G/G-G haplotype, with the lower risk of TRS in females,
but not in males, suggest significant, but sex-specific influence of COMT variants on the
development of treatment-resistance in patients with schizophrenia. However, due to
relatively low number of females, those findings require replication in a larger sample
Triglyceride-rich lipoproteins and novel targets for anti-atherosclerotic therapy
Get PDFAlthough elevated serum low-density lipoprotein-cholesterol (LDL-C) is without any doubts accepted as an important risk factor for cardiovascular disease (CVD), the role of elevated triglycerides (TGs)-rich lipoproteins as an independent risk factor has until recently been quite controversial. Recent data strongly suggest that elevated TG-rich lipoproteins are an independent risk factor for CVD and that therapeutic targeting of them could possibly provide further benefit in reducing CVD morbidity, events and mortality, apart from LDL-C lowering. Today elevated TGs are treated with lifestyle interventions, and with fibrates which could be combined with omega-3 fatty acids. There are also some new drugs. Volanesorsen, is an antisense oligonucleotid that inhibits the production of the Apo C-III which is crucial in regulating TGs metabolism because it inhibits lipoprotein lipase (LPL) and hepatic lipase activity but also hepatic uptake of TGs-rich particles. Evinacumab is a monoclonal antibody against angiopoietin-like protein 3 (ANGPTL3) and it seems that it can substantially lower elevated TGs levels because ANGPTL3 also regulates TGs metabolism. Pemafibrate is a selective peroxisome proliferator-activated receptor alpha modulator which also decreases TGs, and improves other lipid parameters. It seems that it also has some other possible antiatherogenic effects. Alipogene tiparvovec is a nonreplicating adeno-associated viral vector that delivers copies of the LPL gene to muscle tissue which accelerates the clearance of TG-rich lipoproteins thus decreasing extremely high TGs levels. Pradigastat is a novel diacylglycerol acyltransferase 1 inhibitor which substantially reduces extremely high TGs levels and appears to be promising in treatment of the rare familial chylomicronemia syndrome
Use of system dynamics modeling in medical education and research projects
Get PDFThe paper reviews experiences and accomplishments in application of system dynamics modeling in education, training and research projects at the Andrija Štampar School of Public Health, a branch of the Zagreb University School of Medicine, Croatia. A number of simulation models developed over the past 40 years are briefly described with regard to real problems concerned, objectives and modeling methods and techniques used. Many of them have been developed as the individual students' projects as a part of their graduation, MSc or PhD theses and subsequently published in journals or conference proceedings. Some of them were later used in teaching and simulation training. System dynamics modeling proved to be not only powerful method for research and decision making but also a useful tool in medical and nursing education enabling better understanding of dynamic systems' behavior