Prof. Sven Kurbel MD, PhD – personal web pages
Dept. of Physiology, Osijek Medical Faculty
J. Huttlera 4, 31000 Osijek, Croatia
e-mail: sven@jware.hr
11. Can incidence of depression in women be linked to estrogen dependent secretion of
various hormone binding proteins?
Dodig-Curkovic K, Kurbel S, Matic VC.
Med Hypotheses. 2009 Feb;72(2):211-2. doi: 10.1016/j.mehy.2008.09.034. Epub 2008 Nov 8.
Department of Psychiatry, Osijek University Hospital, Osijek, Croatia.
This paper describes a possible framework of hormones and their binding proteins
(BPs) that might be responsible for the increased incidence of depression in
women, including postnatal depression. It is based on three reported facts:
Increased cortisol exposure reduces growth hormone (GH) secretion. Cortisol and
GH show opposite effects on mood. Liver secretion of various hormone binding
proteins is increased under estrogen exposure. If we accept that pure cortisol
exposure leads to depressive mood, while simultaneous brain exposure to cortisol
and an anabolic (growth hormone or somatomammotropin) is less mood affecting, the
occurrence of depression an be more likely in persons: with altered sleep
patterns and thus reduced GH secretion, in individuals with increased chronic
cortisol exposure (any individual under repeated or sustained stress, older
individuals with stressful memories, etc.). The proposed mechanism can be
enhanced in women of reproductive age through increased transcortin and GH BP
pools due to estrogen action on liver. A particularly vulnerable phase seems to
be the early postnatal period, when sudden discontinuation of somatomammotropin
anabolic actions might lead to postnatal depression that takes weeks or months to
resolve, until the GH/cortisol circadian rhythm normalization.
PMID: 18996648 [PubMed – indexed for MEDLINE]
12. Possible links of age related hypertension and evolution imposed features of
heart and aorta.
Kurbel S.
Curr Aging Sci. 2008 Dec;1(3):166-8.
Department of Physiology, Osijek Medical Faculty, Osijek, Croatia. sven@jware.hr
The left ventricle thickness is a limiting factor of optimal heart size and
strength. Due to disappearance of all the features compromising left ventricular
compliance, mammalian heart has decreased vascular density and coronary vessel
diameter and it requires sufficient diastolic aortic pressure for the left
ventricle perfusion. Atrial muscle and the right ventricle are perfused during
the entire heart cycle. The systolic pressure in the left ventricle forces blood
vessels in the muscle wall to collapse, particularly in the subendocardial muscle
layer. This makes the most active part of the heart prone to hypoxia. Optimal
perfusion of the left ventricle wall requires sufficient aortic pressure during
diastole, making individuals with higher diastolic pressures advantageous, in
situations requiring combination of increased heart rate and output. Described
mechanisms might have contributed to the hereditary quality of age-related
hypertension in humans.
PMID: 20021388 [PubMed – indexed for MEDLINE]
13.Are extracellular osmolality and sodium concentration determined by Donnan
effects of intracellular protein charges and of pumped sodium?
Kurbel S.
J Theor Biol. 2008 Jun 21;252(4):769-72. doi: 10.1016/j.jtbi.2008.02.022. Epub 2008 Feb 23.
Department of Physiology, Osijek Medical Faculty, J Huttlera 4, 31000 Osijek,
Croatia. sven@jware.hr
Comment in
J Theor Biol. 2010 May 21;264(2):639-40.
Although we are used to attribute almost identical extracellular fluid (ECF)
sodium concentrations in birds, amphibians, reptiles, and mammals to the
composition of the primordial oceans in which, presumably, all life originated,
this interpretation is not supported by geological data suggesting that the ocean
salinity was never much lower than the present-day values, still four times
higher than our plasma sodium. Here presented interpretation is that the similar
ECF salt concentrations are dictated by the opposed Donnan effects on the cell
membrane. The only way for the cell to reach the osmotic equilibrium is to alter
cell volume, until concentration of nondiffusible intracellular ions (mainly
charges on intracellular proteins) is equal to the ECF restricted ions (mainly
Na+ ions, restricted by pumping out of cells). The achievement of
electroneutrality requires that the sum of all anions equals concentration of
positive ions in the cell (mainly K+). Negative charges on cytoplasmic proteins
are the most stable component among ionized particles and other ions have to
adapt to their concentration. Positive and negative soluble intracellular ions
are all osmotically active and to achieve balance of osmotic forces on the cell
membrane, the sum of their intracellular concentrations must equal the
concentration of osmotically active extracellular particles. Since almost half
the osmotically active ECF particles are sodium ions, the ECF sodium
concentration seems related to concentration of charges on cytoplasmic proteins
and concentration of intracellular phosphates. Our ancestors could not leave the
salty ocean and move to brackish, or even fresh waters, without adequate
regulation of their ECF sodium concentration and osmolality. Concentration of
charges on cytoplasmic proteins or of intracellular phosphate buffers could not
be altered, since this would compromise cell functioning. The remaining solution
was to maintain the lowest ECF Na+ concentration effective in counteracting the
average Donnan effect of charges on cytoplasmic proteins. When the optimal ECF
sodium concentration had once become the reference point for osmoreceptors
(controlling thirst and ADH secretion) and other regulatory mechanisms (secretion
of renin/angiotensin/aldosterone, natriuretic factors), it made an important
survival advantage that allowed spreading of animal life in fresh water and
conquering of earth. The actual common value had to be a compromise that reduces
the average osmotic burden on body cells to zero. Individual cells can reduce
eventual residual osmotic forces on their membrane through altering cell volume
by chloride shift, and by modulating the Na+K+-ATPase function.
PMID: 18374361 [PubMed – indexed for MEDLINE]
14. Comparison of BMI and the body mass/body surface ratio: is BMI a biased tool?
Kurbel S, Zucić D, Vrbanec D, Plestina S.
Coll Antropol. 2008 Mar;32(1):299-301.
Department of Physiology, School of Medicine, University J. J. Strossmayer,
Osijek, Croatia. sven@jware.hr
For decades we are used to judge our body composition by using the body mass
index (BMI). Since the BMI denominator can be considered as a substitute for body
surface area (BSA), the body mass/body surface ratio (BM/BSA) can be calculated.
For a distribution of BM/BSA values comparable to the distribution of normal BMI
values, the range 35.5-39.9 kg/m2 is chosen as normal, although it covers BM
range 50 to 90 kg. The proposed normal BM/BSA range suggests that heavy adults
with less than 2 m of height are not obese only if they are less than 90 kg. If
the described limitations of the BM/BSA ratio are valid, then the BMI should be
regarded as a biased tool, less applicable to individuals with body masses
outside the 55 to 90 kg BM range. If we consider many health problems related to
the increased body mass, it is possible that the BMI should be used with caution
in heavy individuals.
PMID: 18494217 [PubMed – indexed for MEDLINE]
15.Human adiposity, longevity and reproduction features as consequences of
population bottlenecks.
Kurbel S, Zucić D.
Med Hypotheses. 2008;70(5):1054-7. Epub 2007 Oct 31.
Department of Physiology, Osijek Medical Faculty, Osijek, Croatia. sven@jware.hr
A model of the origin of modern humans through several population bottlenecks
caused by glacial cycles and cold-arid periods was used as a frame for describing
occurrence of unique physiological characteristics. Occurrence of regular evening
food sharing among the hominid group members improved their chances of finding
food the next day. It allowed slow emergence of a gracile and energy efficient
phenotype. Improving chances of group survival in the harsh environment included
these traits: – The menstrual cycle occurrence in the common ancestor of human
and great apes. – Single pregnancies only in women with sufficient fat reserves.
Ovulations stop during the food shortage seasons, or longer periods of starvation
and during lactation. – Women prone to obesity sooner become pregnant, passing
the obesity trait as an advantage. – Seldom pregnancies separated by several
years of anovulation made a strong pressure toward the longevity of women and
man. – Menopausis improved the group survival through preventing pregnancy of
women to old to deliver and raise children without significant risks. The modern
times food abundance results in high incidences of adiposity, diabetes and
metabolic syndrome. Continuos ovulations from puberty to menopausis except during
seldom pregnancies and lactations is considered responsible for the occurrence of
estrogen induced breast and endometrial cancers. The combination of longevity
with decades of androgen secretion is the main cause of prostate cancer.
PMID: 17976925 [PubMed – indexed for MEDLINE]
16. The human mind development as a reaction to improvements in memory: possible
consequences on sleep, dreams and psychiatric disorders.
Kurbel S.
Med Hypotheses. 2008;70(3):707-8. Epub 2007 Aug 13.
PMID: 17697755 [PubMed – indexed for MEDLINE]
17. Tumor growth fraction, expression of estrogen and progesterone receptors, p53,
bcl-2 and cathepsin D activity in primary ductal invasive breast carcinoma and
their axillary lymph node metastases.
Kristek J, Dmitrović B, Kurbel S, Sakić K, Krajinović Z, Blazicević V, Has B,
Marjanović K.
Coll Antropol. 2007 Dec;31(4):1043-7.
Division of Thoracic Surgery, Department of Surgery, University Hospital
“Osijek”, Osijek, Croatia.
The aim of this paper is to determine similarities and differences between tumor
cell subclones in cases of ductal invasive breast carcinoma, and which occupy
primary tumor and local axillary lymph metastases. The tumor growth fraction
evaluated by Ki-67 was analyzed along with the expression level of estrogen and
progesterone receptors, protein p53, proto-oncogene protein bcl-2 and cathepsin D
in 60 patients. Metastatic lymph node in axilla has a higher growth fraction of
the tumor cells than the primary tumor (p = 0.045), as well as the higher level
of bcl-2 overexpression (p = 0.014). No statistically significant difference was
found in the presence of immunohistochemically identified estrogen receptors (p =
0.161) and progesterone receptors (p = 0.081) between the primary tumor and the
metastatic lymph node in axilla. Likewise, no difference was found between the
immunohistochemical evaluation of p53 (p = 0.356) and cathepsin D activity (p =
0.928). A higher growth fraction of the tumor cells and the higher level of bcl-2
overexpression in metastatic tumor cells indicate the more aggressive cell
subclones. This study does not support the routine testing of both primary tumor
and locoregional metastasis to evaluate the breast cancer hormone receptor
status.
PMID: 18217456 [PubMed – indexed for MEDLINE]
18. Interstitial hydrostatic pressure: a manual for students.
Kurbel S, Flam J.
Adv Physiol Educ. 2007 Mar;31(1):116-7.
Department of Physiology, Osijek Medical Faculty, Osijek, Croatia. sven@jware.hr
Erratum in
Adv Physiol Educ. 2007 Dec;31(4):392. Sven, Kurbel [corrected to Kurbel, Sven];
Josipa, Flam [corrected to Flam, Josipa].
PMID: 17327592 [PubMed – indexed for MEDLINE]
19. Do high incidences of common neoplasms depend on evolutionary abandoned
regulatory loops revived in tumor cells by mutations?
Kurbel S.
Med Hypotheses. 2007;68(5):991-4. Epub 2006 Dec 4.
Osijek Medical Faculty, Department of Physiology, J Huttlera 4, 31000 Osijek,
Croatia. sven@jware.hr
Neoplasms seem much more common than one might expect, considering complexity of
the required cell malfunctions. It seems very unlikely to get them all set in the
single cell by pure chance. Here presented idea is neoplasms exploit evolutionary
abandoned regulatory mechanisms still contained in our genome. During evolution
numerous changes have occurred in cell biology of multicellular organisms.
Regulatory mechanisms developed, modified its affinity, sensitivity, and effects
on different cells. Some eventually disappeared. Others got another chance to get
involved in something different. Most of these changes are forever lost, but,
inevitably, our genome contains codes for proteins that still can serve abandoned
regulatory mechanisms that are not active in normal cells. Transformation from
normal to malignant cells depends on accumulated alterations that remain
compatible with cell survival and this can happen if alterations critical for
cell survival activate old regulatory loops, obsolete in normal cells. Otherwise,
mutated cells would die before becoming malignant. Based on this concept of
ever-changing cellular function within survival limited borders, living cells can
be considered confined in a well-defined time-space continuum that incorporate
occurrence and disappearance of macromolecules, metabolites, mediators and
physical influences. Numerous scenarios involving the same set of regulatory
proteins emerged during evolution. All survival compatible scenarios were passed
to next generations and many times retested. Evolutionary conservation of
important proteins saved also all existing possibilities of interactions between
them, so parts of abandoned scenarios can be activated in malignant cells. This
box of forgotten tools in our genome might be the prerequisite of high incidences
reported for common neoplasms.
PMID: 17141969 [PubMed – indexed for MEDLINE]
20. Occurrence of the acquired immunity in early vertebrates due to danger of
transmissible cancers similar to canine venereal tumors.
Kurbel S, Plestina S, Vrbanec D.
Med Hypotheses. 2007;68(5):1185-6. Epub 2006 Nov 15.
PMID: 17110053 [PubMed – indexed for MEDLINE]