Arterial hypertension due to fructose ingestion: model based on intermittent osmotic fluid trapping in the small bowel

Based on recently reported data that fructose ingestion is linked to arterial hypertension, a model of regulatory loops involving the colon role in maintenance of fluid and sodium homeostasis is proposed

Evolution of human posture and bipedal locomotion within a provisional time frame of harsh climate changes

In this review paper several emerging issues related to development of human posture and locomotion are arranged in a provisional time frame. Accumulated evidences show that the Eurasian climate was often cold and arid with abundant dust in the atmosphere during the last 500 Ky. These dusty periods of cold, aridity and low insolation lasted from 360 to 340 Kya, 270 to 255 Kya, 170 to 130 Kya, 80 to 60 and finally 40 to 10 Kya. They coincide with migrations of Neanderthals and H. sapiens out of Africa, suggesting that harsh climates might have been important factors in forcing global migrations of our ancestors. When reaching the middle Eurasian latitudes, with reduced sun exposure due to dusty atmosphere and no sea food, our ancestors developed a deficit of vitamin D with compromised locomotion of young individuals due to rickets. This problem of bone maturation made a strong selection pressure toward lighter skin pigmentation. New evidences suggest that skin pigmentation genes in our genome came from the Neanderthals. They have survived several dusty periods, under the selection pressure of becoming pale skinned during their more than 400 Ky in Eurasia. On the other hand, H. sapiens came much later from Africa. Long-legged modern men could easily chase smaller prays, while groups of slower Neanderthals proambushed larger prays. Fossil evidence suggests that both hominid species lived in the same areas for thousands of years, until the final survivors turned out to be mixed individuals, possibly of Caucasian phenotype although with pale skin genes inherited from their Neanderthal ancestors

Similar distributions of Dupuytren\u27s contracture and Y-Chromosome Haplogroup I among modern Europeans suggest simultaneous spreading of these traits some 40 to 10 Kya

A proposition is made that when two independent traits show similar regional patterns of incidence among modern European regions, a plausible expectation is that these two, otherwise unrelated traits, have simultaneously been spread by migration of our ancestors. As a potential example for the proposed concept, distribution of patients with Dupuytren\u27s contracture is here compared with the reported European distribution of Y-Chromosome Haplogroup I, a genetic marker linked to the last glaciation period

A hypothesis of the possible immunological mechanisms behind the chronic gastritis and peptic ulcerations associated with the campylobacter pylori infection

Učinjen je kratki pregled podataka o povezanosti prisustva Campylobacter pylori u bolesnika s kroničnim gastritisom i peptičkim ulceracijama, zajedno s podacima o prisustvu i funkciji mastocita i IgE u sluznici želuca. Ukratko je objašnjeno shvaćanje da se IgE/mastocit sustav razvio tijekom evolucije kao sustav za uzbunjivanje i dovođenje imunokompetentnih stanica u dijelove tijela koji su nedostupniji cirkulirajućim stanicama imunog sustava. Tu spadaju sva rubna tkiva, u što spada i probavna cijev, te interstanični tkivni prostori. Specifičnost i osjetljivost takvog sustava za uzbunjivanje je u direktnoj vezi sa spektrom idiotipova IgE antitijela u cirkulaciji. U želučanoj sluznici je dokazano postojanje mastocita prekrivenih antitijelima klase IgE, te se smatra da su oni lavni izvori oslobađanja histamina unutar sluznice. Uz mogućnost liberalizacije histamina iz mastocita na nespecifič­ ne podražaje, ne može biti isključena mogućnost da je specifična imunološka reakcija IgE/mastocit sistema, nakon susreta sa specifičnim antigenom, glavni izvor oslobođenog histamina u želučanoj sluznici. Učinjena je hipoteza da je posebna fiziološka uloga IgE/ /mastocit sistema u želučanoj mukozi, uz pozivanje imunokompetentnih stanica na mjesto infekcije, također i stvaranje lokalne plime u lučenju želučane kiseline koja olakšava eliminaciju patogena. Kronična infekcija sluznice s C. pylori i sličnim patogenim mogla bi dovesti do permanentne aktivacije ovog sistema, što bi moglo doprinijeti razvoju kronič­nog gastritisa ili nastanku točaka stalne hiperacidnosti pogodnih za nastanak ulkusa. U prilog hipotezi govore nalazi specifičnog humoralnog odgovora na C. pylori u bolesnika s ulkusnom bolešću. Pravu provjeru bi pružile studije sveukupnog i specifičnog IgE u želučanoj sluznici duodenalnih bolesnika i inficiranih eksperimentalnih životinja.A short review of the data regarding the presence of Campylobacter pylori in the peptic ulcer patients and those with chronic gastritis has been presented together with the data regarding the presence and functions of the gastric mucosal mast cells and IgE molecules at their surface. A speculation is made that the physiological role of the IgE/mast cell system in the gastric mucosa, beside bringing the immunocompetent cells to the place of infection, consists also in producing a local tide in the gastric acid secretion that would facilitate pathogen elimination. Chronic infection with C. pylori and other pathogens could lead to the permanent activation of this system resulting in the chronic gastritis or spots of hyperacidity that might turn into ulcers. Findings of the humoral response to C. pylori in ulcer patients support the presented hypothesis. Further studies of the total and specific IgE content in the gastric mucosa of ulcer patients and experimental animals are required to test its validity

A hypothesis of the possible immunological mechanisms behind the chronic gastritis and peptic ulcerations associated with the campylobacter pylori infection

Učinjen je kratki pregled podataka o povezanosti prisustva Campylobacter pylori u bolesnika s kroničnim gastritisom i peptičkim ulceracijama, zajedno s podacima o prisustvu i funkciji mastocita i IgE u sluznici želuca. Ukratko je objašnjeno shvaćanje da se IgE/mastocit sustav razvio tijekom evolucije kao sustav za uzbunjivanje i dovođenje imunokompetentnih stanica u dijelove tijela koji su nedostupniji cirkulirajućim stanicama imunog sustava. Tu spadaju sva rubna tkiva, u što spada i probavna cijev, te interstanični tkivni prostori. Specifičnost i osjetljivost takvog sustava za uzbunjivanje je u direktnoj vezi sa spektrom idiotipova IgE antitijela u cirkulaciji. U želučanoj sluznici je dokazano postojanje mastocita prekrivenih antitijelima klase IgE, te se smatra da su oni lavni izvori oslobađanja histamina unutar sluznice. Uz mogućnost liberalizacije histamina iz mastocita na nespecifič­ ne podražaje, ne može biti isključena mogućnost da je specifična imunološka reakcija IgE/mastocit sistema, nakon susreta sa specifičnim antigenom, glavni izvor oslobođenog histamina u želučanoj sluznici. Učinjena je hipoteza da je posebna fiziološka uloga IgE/ /mastocit sistema u želučanoj mukozi, uz pozivanje imunokompetentnih stanica na mjesto infekcije, također i stvaranje lokalne plime u lučenju želučane kiseline koja olakšava eliminaciju patogena. Kronična infekcija sluznice s C. pylori i sličnim patogenim mogla bi dovesti do permanentne aktivacije ovog sistema, što bi moglo doprinijeti razvoju kronič­nog gastritisa ili nastanku točaka stalne hiperacidnosti pogodnih za nastanak ulkusa. U prilog hipotezi govore nalazi specifičnog humoralnog odgovora na C. pylori u bolesnika s ulkusnom bolešću. Pravu provjeru bi pružile studije sveukupnog i specifičnog IgE u želučanoj sluznici duodenalnih bolesnika i inficiranih eksperimentalnih životinja.A short review of the data regarding the presence of Campylobacter pylori in the peptic ulcer patients and those with chronic gastritis has been presented together with the data regarding the presence and functions of the gastric mucosal mast cells and IgE molecules at their surface. A speculation is made that the physiological role of the IgE/mast cell system in the gastric mucosa, beside bringing the immunocompetent cells to the place of infection, consists also in producing a local tide in the gastric acid secretion that would facilitate pathogen elimination. Chronic infection with C. pylori and other pathogens could lead to the permanent activation of this system resulting in the chronic gastritis or spots of hyperacidity that might turn into ulcers. Findings of the humoral response to C. pylori in ulcer patients support the presented hypothesis. Further studies of the total and specific IgE content in the gastric mucosa of ulcer patients and experimental animals are required to test its validity

Model of congruency determined molecular coevolution: from homophilic binding to ligand/receptor pairs

Peptide hormones depend on reliable recognition by their receptors, based on congruency. If a mutation changes the surface of one of interacting molecules and creates a confined space, a niche, in the otherwise congruent hormone/receptor interface, thiswould allow further mutations confined to the niche space, until one change in molecular shape fills the entire niche space and stops further mutations. Repetition of this process might lead to a different ligand/receptor pair that shows only remote similarities to the initial pair. This paper is aiming to use thismodel of congruency determined coevolution on homophilic membrane molecules to describe evolution of endocrine and paracrine ligands and receptors. During evolution, a gene of some ancient homophilic membrane molecule with intracellular enzymatic activity might have been duplicated. A new pair of genes (A&B) evolved toward heterophilic binding. Expression of molecules from both genes on neighboring cells might allow congruency-determined coevolution that resulted in heterophilic recognition (A-B and B-A). Loss of intracellular domains could make one of heterophilic molecules soluble (protoligands) that recognized membrane molecules on other cells (protoreceptors) as a first ligand/receptor pair. New pairs are formed through gene duplication and separate coevolution leading to families of receptors and families of ligands. Survival pressure forces receptors to remain sensitive and specific, while ligands shrink until they are as small as feasible. Occasionally, plant toxins mimic endogenous peptides (morphine versus endorphins), or receptors can become able to interact with nonpeptide endogenous ligands (steroids, catecholamines). Further receptor evolution congruent to the new ligand can make the initial peptide ligand unrecognizable by that receptor (example: membrane receptors for steroids are without known peptide ligands). Finally, lipid soluble ligands can interact with receptors before receptor molecules reach the cell membrane and are still in the cytoplasm. This can make functional membrane receptors less important (aldosterone, estrogen) or abandoned (other steroids, thyroid hormones)

Shifting paradigms in cancerogenesis: from genetics to epigenetics & back

This review paper is intended to bring together common features of two important new approaches to cancerogenesis. The first is the epigenetic progenitor model of human cancer origin, proposed by Feinberg AP, Ohlsson R & Henikoff S (2), and the second is idea of cancer phenotype hallmarks proposed by Hanahan D & Weinberg RA (6). Both models are briefly described and arguments that these two models are actually explaining the same process from two perspectives are put forward. The second half of the 20th century was a period marked by great advancement inmedicine due to substantial investments in biomedical science. Although acquired knowledge did not have immediate impact on our understanding of development of solidmalignomas, each subsequent decade has revealed new, more complex and well-founded concepts, both in basic medical sciences and in clinical practice

Recidiv karcinoma mokraćnog mjehura i ekspresija biljega Lynch i HER: istraživanje imunohistokemijskih obrazaca u 113 tumora kod 33 bolesnika

The aim was to identify immunohistochemical (IHC) markers able to predict recurrence of urinary bladder tumors. The method of multivariate adaptive regression splines (MARS) was applied to IHC data of 33 patients with urinary bladder cancer that relapsed one to six times (24 male and nine female, age 57-87 years). The MARS analysis was used to predict the total number of recurrences and the Ki-67 value by nine IHC markers (epidermal growth factor receptor (EGFR), HER2, HER3, E-cadherin, Ki-67, MLH1, MSH2, MSH6 and PMS2). Data were divided as initial tumors, first and subsequent recurrences, and tumors that relapsed within nine months of previous surgery or later. The IHC markers were semiquantitatively classified into four groups, as follows: 0 means no positive cells; 1, 10% of positive cells; 2, 11%-30% of positive cells; and 3, 31%-100% of positive cells. In predicting the overall number of recurrences, as a surrogate marker of tumor biology, the R2 value for all tumors was 0.423, for initial tumors 0.686, for first recurrence 0.700, and for subsequent recurrences only 0.233. The key predictors for initial tumors were HER2 and MSH2, while for the first recurrence it was EGFR. For quick recurrences (within nine months), the R2 was 0.474 with EGFR and HER3 as predictors, while for slow recurrences R2 was 0.640 due to EGFR and PMS2. In predicting the Ki-67 value of that tumor, the R2 value for all tumors was 0.300, for initial tumors 0.262, for first recurrence 0.360, and for subsequent recurrences only 0.533. The key predictors for first recurrences were EGFR and MSH6, and for subsequent recurrences HER2, EGFR and all Lynch markers. The R2 was 0.266 for quick recurrences and 0.370 for slow recurrences. The finding of E-cadherin was not found relevant by any of these MARS models. In conclusion, the MARS results associated multiple IHC markers with the number of recurrences and with Ki-67 values. It is important that differences in predictive markers were found between initial tumors and first recurrences, and between quick and slow recurrences, thus suggesting that tumor biology is different among these subgroups regarding the total number of recurrences and Ki-67 values.Cilj rada bio je identificirati imunohistokemijske (IHC) biljege koji mogu predvidjeti recidiv karcinoma mokraćnog mjehura. Metoda multivarijatnih adaptivnih regresijskih splinova (MARS) primijenjena je u IHC podatcima 33 bolesnika s karcinomom mokraćnog mjehura koji se povratio jedan do šest puta (24 muškarca i 9 žena, dob 57-87). Analiza MARS primijenjena je za predviđanje ukupnog broja recidiva i vrijednosti Ki-67 prema devet IHC biljega: receptor epidermalnog faktora rasta (EGFR), HER2, HER3, E-kadherin, Ki-67, MLH1, MSH2, MSH6 i PMS2. Podatci su podijeljeni na početne tumore, prve i naknadne recidive i tumore koji su se vratili unutar devet mjeseci od prethodne operacije ili kasnije. IHC biljezi semikvantitativno su klasificirani u četiri skupine kako slijedi: 0 znači da nema pozitivnih stanica; 1, 10% pozitivnih stanica; 2, 11%-30% pozitivnih stanica; i 3, 31%-100% pozitivnih stanica. U predviđanju ukupnog broja recidiva kao surogat biljega biologije tumora je vrijednost R2 za sve tumore bila 0,423, za početne tumore 0,686, za prvi recidiv 0,700, a za sljedeće recidive samo 0,233. Ključni prediktori za početne tumore bili su HER2 i MSH2, dok je za prvi recidiv bio EGFR. Za brze recidive (u roku od devet mjeseci) R2 je bio 0,474 s EGFR i HER3 kao prediktorima, dok je za spore recidive R2 bio 0,640 zbog EGFR i PMS2. U predviđanju Ki-67 vrijednosti tog tumora vrijednost R2 za sve tumore bila je 0,300, za početne tumore 0,262, za prvi recidiv 0,360, a za sljedeće samo 0,533. Ključni prediktori za prve recidive bili su EGFR i MSH6, a za sljedeće HER2, EGFR i svi biljezi Lynch. R2 je bio 0,266 za brze recidive i 0,370 za spore recidive. Nijedan od ovih modela MARS nije smatrao relevantnim otkriće E-kadherina. Zaključno, rezultati MARS-a povezuju više IHC biljega s brojem recidiva i s vrijednostima Ki-67. Važno je da su pronađene razlike u prediktivnim biljezima između početnih tumora i prvih recidiva te između brzih i sporih recidiva, što ukazuje na to da je biologija tumora različita među ovim podskupinama u pogledu ukupnog broja recidiva i vrijednosti Ki-67

Traganje za neinvazivnom procjenom mišićne slabosti tijekom rada: pruža li rasap podataka visoke rezolucije o električnoj aktivnosti mišića novi uvid?

Paralumbar muscle performance and fatigue were evaluated by measuring electromagnetic activity during entire body vibration (EBV) in 44 healthy subjects. Physical fitness of subjects was estimated on a 5-degree scale. Electric activity was recorded in 200 seconds with 1 kHz sampling on the Biopac Student Lab during EBV. Data were used to produce time series for two vectors of the phase space and spatial axis: X (left-right), Y (up-down) and Z (ventral-dorsal). Time series were evaluated by calculating fractal dimension by the R/S algorithm. Movement of the electric field along the Y-axis showed changes (up-down) extracted in the first and second quarter of the measurement (p=0.02 and p=0.03, respectively). These changes were not specific for gender but showed dependence on subject age and fitness. The fractal dimension values by the R/S algorithm were larger in female subjects. Results suggested the electric field changes during EBV in the up-down direction to contain information on muscular performance and fatigue, not dependent on gender, but on the age and degree of overall physical fitness.Istraživanje električnog polja paralumbalne muskulature kao pokazatelja umaranja provedeno je na 44 zdrava ispitanika, pri čemu je utreniranost njihove paralumbalne muskulature procijenjena anamnestički ljestvicom od 5 stupnjeva. Električna aktivnost snimana je uređajem Biopac Student Lab i uporabom tri para elektroda postavljenih duž osi faznog prostora. Iz prikupljenih podataka izostavljeni su dijelovi koji odgovaraju QRS kompleksu EKG-a i rekonstruirani sljedovi pet različitih načina mjerenja električne aktivnosti, pri čemu su za prva tri izdvojeni zapisi za svaku os. Za os X lijevo i desno, za os Y gore i dolje te za os Z naprijed i nazad, a izračunata su i dva vektora. Iz tako dobivenih vremenskih serija računala se fraktalna dimenzija R/S algoritmom. Od rezultata izračunom fraktal-ne dimenzije zapisa R/S algoritmom izdvaja se kretanje električnog polja duž osi Y (gore-dolje) u prvoj i drugoj četvrtini mjerenja (p=0,02 odnosno p=0,03). Rezultati su se pokazali neovisnima o spolu, ali ovisnima o godinama i utreniranosti ispitanika. Vrijednosti fraktalne dimenzije po R/S algoritmu u žena su bile veće. Navedeno upućuje na to da podaci o kretanju položaja mjerenja duž osi Y (gore-dolje) u sebi sadrže informacije o načinu umaranja muskulature koje nisu ovisne o spolu, nego o dobi i stupnju utreniranosti

Vertiginous syndrome - transcranial doppler analysis of the vertebrobasilar circulation

Svrha ove studije, kao preliminarnog istraživanja, je utvrđivanje utjecaja radiološki vidljivih promjena vratne kralježnice i transkranijskim dopplerom izmjerene brzine protoka u vertebralnim i bazilarnoj arteriji u bolesnika sa vertiginoznim smetnjama. U rad je uključeno 33 bolesnika (16 muškaraca i 17 žena), od kojih je 12 bilo bez, a 21 bolesnik sa radiološki vidljivim promjenama vratne kralježnice. Računata je točnost, te pozitivna prediktivna vrijednost (PPV) radiološkog nalaza vratne kralježnice u razlučivanju bolesnika s normalnom i alteriranom brzinom protoka kao optimalni raspon brzina protoka. Za desnu vertebralnu arteriju točnost radiološkog nalaza je iznosila 0.66, PPV 0.71, fiziološki raspon brzine protoka krvi iznosio je 36±6 cm/s. Za lijevu vertebralnu arteriju točnost radiološkog nalaza bila je 0.60, PPV 0.47, fiziološki raspon brzine protoka 36 ±10 cm/s. Za bazilarnu arteriju točnost radiološkog nalaza je bila 0.66, PPV 0.52 s fiziološkim rasponom brzine protoka krvi 42 ±13 cm/s.The aim of this preliminary study is to estimate the relationship between radiologically visualized changes of the cervical spine and the haemodynamical changes in vertebral and basilar arteries measured by transcranial Doppler in patients suffering from vertiginous syndrome. The report reviewed 33 patients (16 male and 17 female), 12 of whom had no radiologically diagnosed changes of the servical spine, whereas 21 had such changes. Overall accuracy (ACC) and positive predictive value (PPV) of the radiological diagnosis were calculated to determinate the difference between the patients with normal and changed circulation. Overall accuracy of the radiological diagnosis for the right vertebral artery was 0.66, PPV was 0.71, and the physiological mean velocity range was 36+/-6 cm/sec. ACC for the left vertebral artery was 0.60, with PPV being 0.47 and the physiological mean velocity range 36+/-10cm/sec. Additionally, ACC for the basilar artery was 0.66, PPV was 0.52 and the mean velocity range was 42 + /-13cm/sec