Memes: Food for Attitudes and Behavior Crucial for Our Survival.

An effort is made to frame memes within a human evolutionary context in which memes are complex emotion-related tools of enhanced learning and spread of language, art, culture and technology. The basic idea is that any information can become a meme if emotions are evoked in a recipient. The evolution of human brain with memetic capabilities thus produced modern humans.

Are predictions of cancer response to targeted drugs, based on effects in unrelated tissues, the 'Black Swan' events?

Adverse effects of targeted drugs on normal tissues can predict the cancer response. Rash correlates with efficacy of erlotinib, cetuximab and gefitinib and onset of arterial hypertension with response to bevacizumab, sunitinib, axitinib and sorafenib, possible examples of 'Black Swan' events, unexpected scientific observations, as described by Karl Popper in 1935. The proposition is that our patients have individual intrinsic variants of cell growth control, important for tumor response and adverse effects on tumor-unrelated tissue. This means that the lack of predictive side effects in healthy tissue is linked with poor results of tumor therapy when tumor resistance is caused by mechanisms that protect all cells of that patient from the targeted drug effects.

Cystic fibrosis: model of pathogenesis based on the apical membrane potential.

A simple model of cystic fibrosis (CF) is proposed, based on the apical membrane (ApM) potential. The ApM of epithelial cells is highly permeable to sodium and activation of CFTRs makes it permeable to chloride. Calculated ApM potentials of cells with activated cystic fibrosis transmembrane conductance regulators (CFTRs) are between the sodium and chloride Nernst values and thus allow rapid absorption of both ions in exocrine glands. In CF patients the potential is near the sodium Nernst value and thus more salt is left in the ducts. Simulation predicts that the sodium driving force increases more than 3.5 times if the ApM permeability for Cl- increases from 5-94% of the sodium permeability. In pancreatic ductal cells basolateral sodium bicarbonate cotransporters (pNBC1) allows influx of bicarbonates with sodium. Bicarbonates are exchanged for intraductal chloride by anion exchanger 1 (AE1) in the ApM. Activated CFTRs let some chloride to leak back to ducts, followed by water that dilutes ductal proteins. Replenished intraductal chloride allows more bicarbonate secretion. In CF patients, pancreatic water and bicarbonate secretion is limited by the intraductal chloride pool.

Model of pulmonary fluid traffic homeostasis based on respiratory cycle pressure, bidirectional bronchiolo-pulmonar shunting and water evaporation.

The main puzzle of the pulmonary circulation is how the alveolar spaces remain dry over a wide range of pulmonary vascular pressures and blood flows. Although normal hydrostatic pressure in pulmonary capillaries is probably always below 10 mmHg, well bellow plasma colloid pressure of 25 mmHg, most textbooks state that some fluid filtration through capillary walls does occur, while the increased lymph drainage prevents alveolar fluid accumulation. The lack of a measurable pressure drop along pulmonary capillaries makes the classic description of Starling forces unsuitable to the low pressure, low resistance pulmonary circulation. Here presented model of pulmonary fluid traffic describes lungs as a matrix of small vascular units, each consisting of alveoli whose capillaries are anastomotically linked to the bronchiolar capillaries perfused by a single bronchiolar arteriole. It proposes that filtration and absorption in pulmonary and in bronchiolar capillaries happen as alternating periods of low and of increased perfusion pressures. The model is based on three levels of filtration control: short filtration phases due to respiratory cycle of the whole lung are modulated by bidirectional bronchiolo-pulmonar shunting independently in each small vascular unit, while fluid evaporation from alveolar groups further tunes local filtration. These mechanisms are used to describe a self-sustaining regulator that allows optimal fluid traffic in different settings. The proposed concept is used to describe development of pulmonary edema in several clinical entities (exercise in wet or dry climate, left heart failure, people who rapidly move to high altitudes, acute cyanide and carbon monoxide poisoning, large pulmonary embolisms).

Intestinal gases and flatulence: possible causes of occurrence.

All gases entrapped in closed body cavities are destined to be partially or completely absorbed. Intestinal gases often accumulate and cause flatulence. This paper proposes a simple concept of intestinal gas occurrence based on our knowledge on gas resorption in other body cavities. Compliance of intestinal and abdominal walls makes pressure in the liquid chyme bubbles near 760 mmHg. Intestinal gases are from three sources. Air can be swallowed, CO2 come from the gastric acid neutralisation and from intestinal bacterial colonies that also produce hydrogen and methane. In continuously mixed liquid chyme, the total pressure of blood gases is similar or lower than in the venous blood (or=760 mmHg). Some local production of bacterial gases with partial pressure of more than 90 mmHg is required, so the resulting small bowel bubbles would contain less than 20% of bacterial gases. If peristaltic mixing of chyme is prevented by an obstacle, local pressures of bacterial gases build up, form bubbles that fuse and finally make X-ray visible aeroliquid levels. Bacterial gases make almost 3/4 of the flatulence. Formation of bubbles destined to become flatulence might depend on altered rheological condition of the large bowel content, with local abundant production of bacterial gases near bacterial colonies. Gases are unable to diffuse rapidly through the dense liquid content and local accumulation allows formation of bubbles mainly of bacterial gases. Their pressure can be higher 760 mmHg, since they are stretching the thick content. Poor diffusion of gases keeps them almost free of blood gases and their entrance makes them bigger. As the content moves along the colon, the content is becoming more solid and gases are becoming entrapped in large bubbles. Some blood and bacterial gases are absorbed and exhaled, but the remaining quantity has no other escape except flatulence. Flatulence rich in bacterial gases might be the price for the large bowel water reabsorption. It seems that beside the peroral use of antibiotics active in the colon, little can be done to reduce flatulence.

A model of dual circulation in liver acini with hypoxia regulated adenosine secretion.

It was postulated by W.W. Lautt that the hepatic artery flow compensation for changes in portal vein flow (the 'hepatic arterial buffer response') is regulated through the portal blood washout of adenosine from the small fluid compartment that surrounds the hepatic arterial resistance vessels. It is presumed that the adenosine secretion there is constant and independent of oxygen supply or liver demand. It was reported by others that liver secretes variable quantities of adenosine and that secretion is related to the level of liver hypoxia. This paper is an attempt to describe a model of acinar circulation without sources of constant adenosine secretion. The presented model is based on the fact that portal blood enters acinar space near the vascular stalk in the zone 1, while most of the arterial branches empty one-third from the interlobular septa, at the beginning of the zone 2, just downstream from the zone 1. Another important characteristic of liver architecture is that near 5/9 of lobular volume is in the zone 1. Liver cells in zone 1 are well oxygenated by the portal blood and they have low adenosine secretion that might seem almost constant. Since most arterial branches empty more peripherally, the zone 1 normally does not depend on the arterial circuit and most of arterial branches are governed by the adenosine secretion from the upstream zone 1. Low portal flow, would increase adenosine secretion from the zone 1 and thus dilate numerous downstream arterial resistance vessels. An increased flow from these arterial vessels would compensate any decrease in the portal flow. Zones 2 and 3 probably have higher adenosine secretion rates since the oxygenation depends on the amount of added arterial blood and on the liver cell metabolism. Some of the arterial branches in those zones are probably open all the time, preserving them zones from hypoxic injury. Since the main point for arterial inflow is concentrated downstream from the zone 1, in cases of low portal pressures, or elevated upstream resistance, some of the arterial blood might leave the acinus in retrograde direction via the portal branch and enter some other acinus as a part of portal blood. These arterio-portal communications might be important in cases of low or none portal flow when zone 1 is in hypoxia. In the 3D liver space with tightly packed acini, very complex and ever-changing patterns of combined antegrade and retrograde flows can be expected.

Inertia of endocrine systems due to hormone binding to circulatory proteins.

It is often presumed that the main role of hormone binding to albumins and binding proteins (BPs) is to reduce oscillating levels of free hormone molecules and to transport steroid hormones. This paper is an attempt to define possible consequences of hormone molecules binding to carrier proteins in circulation. Binding to albumins and BPs prevents exact and quick control of hormone actions. Hormones without significant protein binding govern vital and fast acting regulatory mechanisms (blood glucose or calcium) in which any added inertia might be dangerous. In the presented model, the added inertia for a partially bound hormone (H) is defined as: H(bound)/H(free). Values, calculated from the reported data, range from 0.4 for GH to more than 2000 for T(4). In comparison to albumins, high-affinity BPs make more stable reserve that would cover periods of low or no hormone secretion. At the same time, hormone molecules are taken away from the blood level control and thus might be considered sequestrated. For hormones without protein binding, the well-perfused areas of the body, or the areas with increased capillary permeability, would be more exposed, making an uneven distribution among target tissues. For the hormone that binds blood proteins, places of secretion and tissue perfusion become unimportant, since the hormone is being liberated anywhere in the circulation (i.e., for strongly bound IGFs, IGF binding proteins do not just stabilize proinsulin actions of IGF-1, but also make all parts of body to be under the same exposure to liberated IGFs, an important feature to promote a symmetrical bone growth). Estrogens are known to stimulate liver secretion of different BPs. A possible explanation is that in the follicular phase there is a small initial mass of granulosa cells, and it takes time to saturate free estrogen carriers, before the normal free hormone level can be reached and FSH secretion inhibited. Less inert peptide inhibin might suppress FSH before free estrogens reach the required level. Without inhibin suppression, an increased FSH level with an increased number of growing follicles can be expected. Estrogens increased production of BPs augments inertia of the estrogen loop and possibly modulates the FSH/estrogen negative feedback.