Diabetic retinopathy (DR) is one of the most common microvascular complications of diabetes mellitus (DM) and a leading cause of blindness in working-age adults in developed countries. Numerous ...investigations have recognised inflammation and angiogenesis as important factors in the development of this complication of diabetes. Current methods of DR treatment are predominantly used at advanced stages of the disease and could be associated with serious side effects. Therefore, new diagnostic methods are needed in order to identify the initial stages of DR as well as monitoring the effects of applied therapy. Biochemical biomarkers are molecules found in blood or other biological fluid and tissue that indicate the existence of an abnormal condition or disease. They could be a valuable tool in detecting early stages of DR, identifying patients most susceptible to retinopathy progression and monitoring treatment outcomes. Biomarkers related to DR can be measured in the blood, retina, vitreous, aqueous humour and recently in tears. As the retina represents a small part of total body mass, a circulating biomarker for DR needs to be highly specific. Local biomarkers are more reliable as indicators of the retinal pathology; however, obtaining a sample of aqueous humour, vitreous or retina is an invasive procedure with potential serious complications. As a non-invasive novel method, tear analysis offers a promising direction in further research for DR biomarker detection. The aim of this paper is to review systemic and local inflammatory and angiogenic biomarkers relevant to this sight threatening diabetic complication.
Although breast cancer (BC) occurs more often in older women, it is the most commonly diagnosed malignancy in women of childbearing age. Owing to the overall advancement of modern medicine and the ...growing global trend of delaying childbirth until later age, we find ever more younger women diagnosed and treated for BC who have not yet completed their family. Therefore, fertility preservation has emerged as a very important quality of life issue for young BC survivors. This paper reviews currently available options for fertility preservation in young women with early-stage BC and highlights the importance of a multidisciplinary approach to fertility preservation as a very important quality of life issue for young BC survivors. Pregnancy after BC treatment is considered not to be associated with an increased risk of BC recurrence; therefore, it should not be discouraged for those women who want to achieve pregnancy after oncologic treatment. Currently, it is recommended to delay pregnancy for at least 2 years after BC diagnosis, when the risk of recurrence is highest. However, BC patients of reproductive age should be informed about the potential negative effects of oncologic therapy on fertility, as well as on the fertility preservation options available, and if interested in fertility preservation, they should be promptly referred to a reproductive specialist. Early referral to a reproductive specialist is an important factor that increases the likelihood of successful fertility preservation. Embryo and mature oocyte cryopreservation are currently the only established fertility preservation methods but they require ovarian stimulation (OS), which delays initiation of chemotherapy for at least 2 weeks. Controlled OS does not seem to increase the risk of BC recurrence. Other fertility preservation methods (ovarian tissue cryopreservation, cryopreservation of immature oocytes and ovarian suppression with gonadotropin-releasing hormone agonists) do not require OS but are still considered to be experimental techniques for fertility preservation.
Hyperhomocysteinaemia is a risk factor for ischemic stroke development. Single nucleotide variation in the methylenetetrahydrofolate reductase gene (MTHFR, C677T polymorphism, T allele) causes a ...Ala222Val mutation that is associated with hyperhomocysteinemia, cardiovascular disease and stroke. The homozygous TT genotype of MTHFR may also be linked to tobacco smoking in patients from distinct demographic groups. This study evaluated the association of T allele with smoking in a cohort of 301 Croatian adults, including 187 healthy controls and 114 patients with ischemic stroke (IS) and proven ischemic cerebral infarction based on Computed Tomography (CT). Exclusion criteria were hemorrhagic cerebral infarction on CT scan, medical history of diabetes mellitus, and age (>60 years). Cholesterol, triglycerides (TG), low-density lipoprotein (LDL), high-density lipoprotein (HDL) and C-reactive protein (CRP) were biochemically analyzed. A positive correlation between the TT genotype of MTHFR and smoking was observed within our entire study cohort (p = 0.011). In the control group, the relative frequency of the TT genotype in smokers is complemented by the prevalence of the CC genotype among non-smokers. Hence, our study with Croatian subjects corroborates previous studies indicating that the TT MTHFR variant is linked to smoking. This positive correlation between the TT genotype and smoking represents a confounding parameter that must be accounted for to permit evaluation of statistical associations with stroke and biochemical markers in blood and single nucleotide variations in the MTHFR gene.
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Cilj ovog preglednog rada je prikazati suvremene mogućnosti očuvanja plodnosti kod mladih žena s ginekološkim tumorima (rakom jajnika, trupa maternice ili vrata maternice). S obzirom na rizike i ...koristi metoda za očuvanje plodnosti, preporuča se bolesnicu prijeterapijski prezentirati na multidisciplinarnom timu koji uključuje ginekologa, ginekološkog onkologa, embriologa, radiologa, patologa i reprodukcijskog endokrinologa. Samo je mali udio bolesnica s epitelnim rakom jajnika ili granično malignim tumorom janika prikladan za očuvanje plodnosti (FIGO IA I IC). Nakon operacijskog uklanjanja jajnika, tkivo jajnika ili jajne stanice se krioprezervaju; nakon završetka onkološkog liječenja obično slijedi ortotopična retransplantacija ovarijskog tkiva bolesnici, dok se jajne stanice mogu koristiti u postupku izvantjelesne oplodnje. Nakon liječenja uz očuvanje plodnosti kod odabranih bolesnica rakom jajnika stopa živorođenih kretala se do 53,8%. Kod bolesnica s rakom endometrija očuvanje plodnosti podrazumijeva očuvanje maternice. Bolesnice pogodne za očuvanje plodnosti su mlađe žene sa dobro diferenciranim tumorom koji ne prodire u miometrij. Za očuvanje plodnosti kod raka endometrija primjenjuje se hormonsko liječenje, utemeljeno na gestagenima, koji stabiliziraju i zaustavljaju nekontroliranu estrogensku stimulaciju endometrija. Po završetku liječenja potrebni su učestali kontrolni pregledi, a uzimanje tkiva sluznice (kiretaža ili biopsija endometrija) predstavljaju standard u praćenju ovih bolesnica. Nakon liječenja gestagenima stopa živorođenih kreće se oko 60% ili čak više kod primjene postupaka potpomognute oplodnje. Očuvanje plodnosti kod karcinoma vrata maternice moguće je kod strogo odabrane skupine bolesnica (FIGO IA1, IA2 ili IB1) motiviranih za trudnoću; kod tih bolesnica konizacija ili biopsija konizata u kombinaciji s laparoskopskom limfadenektomijom predstavlja najprikladniji zahvat sa stopom trudnoća do 47%.
We highlight the particular aspects of the stable gastric pentadecapeptide BPC 157 pleiotropic beneficial activity (not destroyed in human gastric juice, native and stable in human gastric juice, as ...a cytoprotection mediator holds a response specifically related to preventing or recovering damage as such) and its possible relations with neurotransmitter activity. We attempt to resolve the shortage of the pleiotropic beneficial effects of BPC 157, given the general standard neurotransmitter criteria, in classic terms. We substitute the lack of direct conclusive evidence (i.e., production within the neuron or present in it as a precursor molecule, released eliciting a response on the receptor on the target cells on neurons and being removed from the site of action once its signaling role is complete). This can be a network of interconnected evidence, previously envisaged in the implementation of the cytoprotection effects, consistent beneficial particular evidence that BPC 157 therapy counteracts dopamine, serotonin, glutamate, GABA, adrenalin/noradrenalin, acetylcholine, and NO-system disturbances. This specifically includes counteraction of those disturbances related to their receptors, both blockade and over-activity, destruction, depletion, tolerance, sensitization, and channel disturbances counteraction. Likewise, BPC 157 activates particular receptors (i.e., VGEF and growth hormone). Furthermore, close BPC 157/NO-system relations with the gasotransmitters crossing the cell membrane and acting directly on molecules inside the cell may envisage particular interactions with receptors on the plasma membrane of their target cells. Finally, there is nerve-muscle relation in various muscle disturbance counteractions, and nerve-nerve relation in various encephalopathies counteraction, which is also exemplified specifically by the BPC 157 therapy application.
Premda se karcinom dojke češće javlja u starijoj životnoj dobi, to je i najučestaliji malignitet u žena reproduktivne dobi. Zbog sveukupnog napretka moderne medicine i rastućeg globalnog trenda ...odgađanja rađanja djece za kasniju dob suočavamo se sa sve više mladih žena s dijagnosticiranim i liječenim karcinomom dojke koje još nisu kompletirale obitelj. Stoga je područje očuvanja plodnosti postalo jako bitno u očuvanju kvalitete života mladih žena koje su preboljele karcinom dojke. Ovaj rad iznosi trenutno dostupne metode za očuvanje plodnosti u mladih žena s ranim karcinomom dojke i ističe važnost
multidisciplinarnog pristupa u očuvanju plodnosti kao bitnog čimbenika kvalitete života tih žena. Smatra se da trudnoća nakon karcinoma dojke nije povezana s povišenim rizikom od recidiva pa stoga ne treba obeshrabriti žene koje žele ostvariti trudnoću nakon provedenog onkološkog liječenja. Danas se preporuča pričekati s trudnoćom barem 2 godine nakon postavljene dijagnoze za vrijeme kada je rizik od povrata bolesti najveći. No, isto tako bi bolesnice reproduktivne dobi trebalo obavijestiti o mogućem negativnom učinku onkološke terapije na plodnost te o dostupnim metodama očuvanja plodnosti i u slučaju zainteresiranosti za očuvanje plodnosti bolesnice treba žurno uputiti reproduktivnom specijalistu. Rano upućivanje reproduktivnom specijalistu je bitan čimbenik koji povećava izglede za uspješno očuvanje plodnosti. Krioprezervacija embrija i zrelih oocita su trenutno jedine standardne metode očuvanja plodnosti koje zahtijevaju stimulaciju ovarija kojom se odgađa početak kemoterapijskog liječenja barem 2 tjedna. Smatra se da kontrolirana stimulacija ovarija ne povećava rizik od povrata karcinoma dojke. Druge metode očuvanja plodnosti (krioprezervacija tkiva jajnika, krioprezervacija nezrelih oocita,
ovarijska supresija GnRH agonistima) ne zahtijevaju primjenu ovarijske stimulacije, ali se i dalje smatraju eksperimentalnim metodama za očuvanje plodnosti.
It is generally accepted that hydrocephalus is a consequence of the disbalance between cerebrospinal fluid (CSF) secretion and absorption which should in turn lead to CSF pressure gradient ...development and ventricular enlargement. To test CSF pressure gradient role in hydrocephalus development, we experimentally caused CSF system impairment at two sites in cats. In the first group of animals, we caused Sylvian aqueduct obstruction and recorded CSF pressure changes pre and post obstruction at three measuring sites (lateral ventricle -LV, cortical-CSS and lumbar subarachnoid space -LSS) during 15 min periods and in different body positions over 360 degrees. In the second group of experiments, we caused cervical stenosis by epidural plastic semiring implantation and monitored CSF pressure changes pre and post stenosis implantation at two measuring sites (lateral ventricle and lumbar subarachnoid space) during 15 min periods in different body positions over 360 degrees. Both groups of experimental animals had similar CSF pressures before stenosis or obstruction at all measuring points in the horizontal position. During head-up verticalization, CSF pressures inside the cranium gradually became more subatmospheric with no significant difference between LV and CSS, as they are measured at the same hydrostatic level, while CSF pressure inside LSS became more positive, causing the development of a large hydrostatic gradient between the cranial and the spinal space. With cervical stenosis, CSF pressure inside the cranium is positive during head-up verticalization, while in cats with aqueductal obstruction CSF pressure inside the CSS remains negative, as it was during control period. Concomitantly, CSF pressure inside LV becomes less negative, thus creating a small hydrostatic gradient between LV and CSS. Since CSF pressure and gradient changes occur only by shifting body position from the horizontal plane, our results indicate that cervical stenosis in a head-up vertical position reduces blood perfusion of the whole brain, while aqueductal obstruction impairs only the perfusion of the local periventricular brain tissue. It seems that, for evolutionary important bipedal activity, free craniospinal communication and good spinal space compliance represent crucial biophysical parameters for adequate cerebral blood perfusion and prevention of pathophysiological changes leading to the development of hydrocephalus.
Intracranial hypertension is a severe therapeutic problem, as there is insufficient knowledge about the physiology of cerebrospinal fluid (CSF) pressure. In this paper a new CSF pressure regulation ...hypothesis is proposed. According to this hypothesis, the CSF pressure depends on the laws of fluid mechanics and on the anatomical characteristics inside the cranial and spinal space, and not, as is today generally believed, on CSF secretion, circulation and absorption. The volume and pressure changes in the newly developed CSF model, which by its anatomical dimensions and basic biophysical features imitates the craniospinal system in cats, are compared to those obtained on cats with and without the blockade of craniospinal communication in different body positions. During verticalization, a long-lasting occurrence of negative CSF pressure inside the cranium in animals with normal cranio-spinal communication was observed. CSF pressure gradients change depending on the body position, but those gradients do not enable unidirectional CSF circulation from the hypothetical site of secretion to the site of absorption in any of them. Thus, our results indicate the existence of new physiological/pathophysiological correlations between intracranial fluids, which opens up the possibility of new therapeutic approaches to intracranial hypertension.
Introduction
The pathophysiology, diagnosis, and management of idiopathic normal pressure hydrocephalus (iNPH) remain unclear. Although some prognostic tests recommended in iNPH guidelines should ...have high sensitivity and high predictive value, there is often no positive clinical response to surgical treatment.
Materials and methods
In our study, 19 patients with clinical and neuroradiological signs of iNPH were selected for preoperative evaluation and possible further surgical treatment according to the guidelines. MR volumetry of the intracranial and spinal space was performed. Patients were exposed to prolonged external lumbar drainage in excess of 10 ml per hour during 3 days. Clinical response to lumbar drainage was assessed by a walk test and a mini-mental test.
Results
Twelve of 19 patients showed a positive clinical response and underwent a shunting procedure. Volumetric values of intracranial space content in responders and non-responders showed no statistically significant difference. Total CSF volume (sum of cranial and spinal CSF volumes) was higher than previously published. No correlation was found between spinal canal length, CSF pressure, and CSF spinal volume. The results show that there is a significantly higher CSF volume in the spinal space in the responder group (
n
= 12) (120.5 ± 14.9 ml) compared with the non-responder group (103.1 ± 27.4 ml;
n
= 7).
Discussion
This study demonstrates for the first time that CSF volume in the spinal space may have predictive value in the preoperative assessment of iNPH patients. The results suggest that patients with increased spinal CSF volume have decreased compliance. Additional prospective randomized clinical trials are needed to confirm our results.
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