In experimental studies, the intraperitoneal administration of heparin has been shown to attenuate cancer growth, reduce the formation of postoperative adhesions and possess immunomodulatory properties of oncological benefit for peritoneal carcinomatosis of colorectal cancer origin. Combined with data suggesting that the intraperitoneal administration of heparin can reduce the permeability and increase the ultrafiltration of the peritoneal membrane, we hypothesize that intraperitoneally administrated heparin could be a useful adjunction to the currently used hyperthermic intraperitoneal chemotherapy (HIPEC) regimens.

The science of osteoimmunology, a relatively new field of research, reveals the important interactions between the immune system and skeletal system. Interactions occur between prostaglandin metabolism, inflammatory proteins and bone metabolism. Systemic as well as local sources of inflammation appear to be actively involved in both bone formation and resorption. Non Steroidal Anti-Inflammatory Drugs (NSAIDs) can play a detrimental role in bone fractures, opposing the aim of the intervention, and can have such a negative impact on the synthesis of prostaglandins that they could even promote bone resorption. When used for a prolonged time, NSAIDs can also cause the development of an inflammatory cascade starting from the gastro-intestinal system, possibly resulting in bone resorption. Several studies show that the use of either selective or non-selective NSAIDs are intimately related to disturbances in immunological allostasis, bone metabolism and the inhibition or impediment of bone healing.

The range of symptoms and clinical syndromes subsumed under the rubric "depression" is remarkably large. It covers the lay use of the word to describe transient sad feelings on the one hand and a devastating biological illness on the other. In consequence, society has failed to grasp that severe mood disorders do, in fact, represent life-threatening medical illness. In the present article, we outline the major historical and contemporary contributors to the present misapprehension of this severe illness and discuss the serious consequences for diagnosis, treatment, and clinical research. We suggest potential categorical and terminological revisions to current formulations of the disease and emphasize that being severely ill involves much more than is subsumed by the term "depression".

The main physiological function of vitamin D is maintenance of calcium homeostasis by its effect on calcium absorption, and bone health in association with parathyroid gland. Vitamin D deficiency (VDD) is defined as serum 25-hydroxy vitamin D (25OHD) levels <20ng/ml. Vitamin D insufficiency is called when serum 25OHD levels are between 20-29ng/ml, though existence of this entity has been questioned. Do all subjects with VDD have clinical disease according to this definition? Analysis of published studies suggests that calcium absorption in inversely correlated with serum 25OHD levels and calcium intake. We hypothesize that there exist an intestinal calcistat, which controls the calcium absorption independent of PTH levels. It consists of calcium sensing receptor (CaSR) on intestinal brush border, which senses calcium in intestinal cells and vitamin D system in intestinal cells. CaSR dampens the generation of active vitamin D metabolite in intestinal cells and decrease active transcellular calcium transport. It also facilitates passive paracellular diffusion of calcium in intestine. This local adaptation adjusts the fractional calcium absorption according the body requirement. Failure of local adaptation due to decreased calcium intake, decreased supply of 25OHD, mutation in CaSR or vitamin D system decreases systemic calcium levels and systemic adaptations comes into the play. Systemic adaptations consist of rise in PTH and increase in active vitamin D metabolites. These adaptations lead to bone resorption and maintenance of calcium homeostasis. Not all subjects with varying levels of VDD manifest with secondary hyperparathyroidism and decreased in bone mineral density. We suggest that rise in PTH is first indicator of VDD is rise in PTH along with decrease in BMD depending on duration of VDD. Hence, subjects with any degree of VDD with normal PTH and BMD should not be labeled as vitamin D deficient. These subjects can be called subclinical VDD, and further studies are required to assess beneficial effect of vitamin D supplementation in this subset of population. This hypothesis further highlights pitfalls in treatment of hypoparathyroidism.

The exact mechanism by which cytotoxic ribonucleases reach the cytosol of tumor cells remains unclear. The interaction of ribonucleases with a lipid bilayer is involved in the translocation of ribonucleases across the endosomal membrane. Here, we aimed to study the hydropathy character of toxic antitumor ribonucleases (bovine seminal ribonuclease and binase) and two non-toxic ribonucleases (bovine pancreatic ribonuclease and human pancreatic ribonuclease) by sliding-window hydrophobicity analysis. Comparative hydropathy plot analysis of the non-toxic pancreatic ribonucleases and their toxic variants was also performed. The data obtained indicate that some cytotoxic ribonucleases have a hydrophobic segment, which is sterically available for the hydrophobic interaction with a tumor cell membrane and endosomal membrane. After dissociation, subunits of dimeric ribonucleases are probably capable of thermodynamically favorable interaction with the interfacial region of a lipid bilayer. Remarkably the hydrophobic segment is not identified in the amino acid sequences of non-toxic ribonucleases. The paper describes the hydrophobic properties of toxic RNases that are essential for both the model of a lipid-protein interaction and the cytotoxicity mechanism unraveling.

Activities of both autonomic nervous system divisions, sympathetic and parasympathetic, are dual - continuous, tonic and changing, modulating. Tonic activity domination accompanies stationary (patho)physiological conditions, while modulating activity occurs with the change of stimuli. The intensity of the two activities is inversely proportional. In patients with heart failure, spectral analysis of heart rate variability displays reduced sympathetic modulation activity during illness, as a logical consequence of an increased sympathetic tone. On the other hand, vagal modulation activity slightly decreases or does not change at the very early stage of disease, soon afterwards it increases, and after a certain period of time, with the progression of the disease, vagal modulation decreases, and finally disappears. These changes reveal sequential response of vagal tone to the progression of heart failure and consequent sympathicotonia; slight initial oscillation or unresponsiveness, soon followed by self-suppression, and then, in an advanced heart failure, by counteraction to the sympathicotonia. This model of polyphasic reaction of vagal system, dependent on the stage of heart failure, challenges traditional concept of sympathovagal interaction. By this hypothesis, the self-suppression of vagal tone occurs in order to enable full sympathetic activation of compensatory mechanisms which aim to correct hemodynamic deterioration. Once the sympathicotonia becomes inefficient and even harmful, counter-regulatory increase in vagal tone develops, in order to decrease oxygen consumption and preserve or possibly enhance residual systolic and diastolic cardiac function. Decreased vagal tonic activity is probably mediated centrally. Later increase of vagal tone is probably triggered by an increased concentration of natriuretic peptides. The existence of predominantly adrenergic IL, Ca and predominantly cholinergic IK, Ach currents and of a common If current in sinoatrial nodal cells enables such dual - synergistic and antagonistic - sympatho-vagal relationship. In conclusion, a complex, polyphasic vagal reaction to the sympathicotonia and heart failure progression is suggested by the hypothesis. Clinical and experimental studies based on this hypothesis will probably allow better insight into autonomic functions.

HIV-infected individuals undergoing long-term anti-retroviral treatment tend to show premature senescence. Accelerated mitochondrial aging induced by nucleoside reverse transcriptase inhibitors (NRTIs) has been implicated as a part of this phenomenon. Traditionally, this has been attributed to inhibition of mtDNA polymerase γ by these drugs, but alternative explanations have been proposed. It is known that NRTIs can not only inhibit viral reverse transcriptase, but also human telomerase. A number of extratelomeric roles of telomerase, including protection of mitochondrial DNA and function, have emerged recently. In this paper, I propose that inhibition of mitochondrial telomerase activity by NRTI drugs contributes to the mitochondrial toxicity and premature aging seen in treated HIV patients, and discuss objections and experimental testing of the hypothesis.

The oxygen saturation of the systemic arterial blood is associated with the adequacy of respiration, and can be measured non-invasively by pulse oximetry in the systemic tissue. The oxygen saturation of the blood in the pulmonary artery, the mixed venous blood, reflects the balance between oxygen supply to the systemic tissues and their oxygen demand. The mixed venous oxygen saturation has also clinical significance because it is used in Fick equation for the quantitative measurement of cardiac output. At present the measurement of the mixed venous oxygen saturation is invasive and requires insertion of a Swan-Ganz catheter into the pulmonary artery. We suggest a noninvasive method for the measurement of the mixed venous oxygen saturation in infants, pulmonary pulse oximetry. The method is similar to the systemic pulse oximetry, which is based on the different light absorption curves of oxygenated and deoxygenated hemoglobin and on the analysis of photoplethysmographic curves in two wavelengths. The proposed pulmonary pulse oximeter includes light-sources of two wavelengths in the infrared, which illuminate the pulmonary tissue through the thoracic wall. Part of the light which is scattered back from the pulmonary tissue and passes through the thoracic wall is detected, and for each wavelength a pulmonary photoplethysmographic curve is obtained. The pulmonary photoplethysmographic curves reflect blood volume increase during systole in the pulmonary arteries in the lung tissue, which contain mixed venous blood. The ratio R of the amplitude-to-baseline ratio for the two wavelengths is related to the mixed venous oxygen saturation through equations derived for the systemic pulse oximetry. The method requires the use of extinction coefficients values for oxygenated and deoxygenated hemoglobin, which can be found in the literature.

Malignant otitis externa (MOE) usually affect patients with systemic diseases, especially diabetes mellitus. MOE is a mainly unilateral disease. Given that around 90% of human adults are right-handed we hypothesized that hand preference might be one of the factors involved in the development of MOE. All 38 of the patients whom we treated for MOE between August 2009 and November 2012 (28 males and 10 females, age range 43-91years) had poorly controlled diabetes mellitus, and all of them reported itching in the involved ear. The difference in the laterality of MOE among our right- and left-handed subjects was significant: right hand dominance was associated mostly with right-sided MOE (24/34) and left hand dominance was associated with occurrence of MOE only in the left ears (4/4, p=0.006). These findings point to an unexpectedly strong relationship between the patient's handedness and laterality of his/her MOE, leading us to hypothesize that the development of MOE might be attributable to self-inflicted local trauma to the ear canal on the same side as the dominant hand.