Radivoje Radić

Function of circle of Willis

Nearly 400 years ago, Thomas Willis described the arterial ring at the base of the brain (the circle of Willis, CW) and recognized it as a compensatory system in the case of arterial occlusion. This theory is still accepted. We present several arguments that via negativa should discard the compensatory theory. (1) Current theory is anthropocentric; it ignores other species and their analog structures. (2) Arterial pathologies are diseases of old age, appearing after gene propagation. (3) According to the current theory, evolution has foresight. (4) Its commonness among animals indicates that it is probably a convergent evolutionary structure. (5) It was observed that communicating arteries are too small for effective blood flow, and (6) missing or hypoplastic in the majority of the population. We infer that CW, under physiologic conditions, serves as a passive pressure dissipating system; without considerable blood flow, pressure is transferred from the high to low pressure end, the latter being another arterial component of CW. Pressure gradient exists because pulse wave and blood flow arrive into the skull through different cerebral arteries asynchronously, due to arterial tree asymmetry. Therefore, CW and its communicating arteries protect cerebral artery and blood–brain barrier from hemodynamic stress.

Prevalence of the palmaris longus in relation to the hand dominance

PurposeThe incidence of left-handedness in the general population is between 8 and 15%. There is a presumption that the prevalence of palmaris longus muscle differ between right-handed and left-handed people. This prospective study was conducted to determine the prevalence of the palmaris longus in relation to the hand dominance.MethodsThe study included 542 subjects (216 male and 326 female). They were initially tested to hand dominance and after that they were asked to do the standard test (Schaeffer’s test) for the assessment of the palmaris longus tendon. If the tendon was not visualized or palpable, four additional tests (Thompson’s test, Mishra’s tests I and II, Pushpakumar’s “two-finger sign” method) were done to confirm its absence.ResultsRight hand dominance was recorded in 452 (83.4%) subjects while the left hand dominance was recorded in 90 (16.6%) subjects. In right-handed subjects, palmaris longus tendon was absent on the right side in 24 (5.3%) and on the left side in 50 (11.1%) cases. In left-handed subjects, it was absent on the right side in 18 (20%) and on the left side in 2 (2.2%) cases. These differences were statistically significant. Bilateral absence of palmaris longus tendon was similar in both examined groups (25.1% in the overall series, 24.3% in right-handed subjects, 28.9% in left-handed subjects).ConclusionsThe results of our study show that a right-sided absence was more common in left-handed persons while the left-sided absence was more common in right-handed persons. Unilateral tendon absence was more common on the non-dominant hand.

A calcium homeostasis model: orchestration of fast acting PTH and calcitonin with slow calcitriol

Calcitriol is in plasma bound to transcalciferin and this results in a long calcitriol half-life in plasma (5-12h). Abundance of bound calcitriol molecules prevents the exact and quick control of its effects and makes it an inert regulator with a time lag between the changes of calcitriol synthesis and its effect on peripheral tissues. The added regulatory inertia is here defined as: calcitriol(bound)/calcitriol(free) and it approaches value of 99. Estrogens increase transcalciferin levels. It is possible that the estrogen-induced increase in the total calcitriol plasma pool makes calcitriol effects even more inert, augmenting and prolonging the calcitriol effects and thus improving calcium balance in women. Since calcitriol synthesis in kidneys depends on the PTH level, it can be assumed that the size of the total calcitriol pool in plasma reflects more the average PTH secretion during previous hours, than the high or low peaks of PTH secretion in the same period. In other words, one or more PTH tides of short duration are followed with a late calcitriol tide that lasts for hours, and even longer lasting rise in calcitriol effects. Bone integrity depends also on the cortisol level. A possible speculation is that the main result of all profound bone effect of hypecortisolemia, might be reduction of the bone amino acids uptake, thus allowing redistribution of available proteins. Both PTH and calcitriol prevent dangerous hypocalcemia. PTH is quick in mobilizing bone calcium, while calcitriol tends to increase absorption of dietary calcium. In case of low or no dietary calcium, calcitriol mobilizes bone calcium and thus increase PTH initiated demineralization. In the case of calcium abundance, increased plasma calcium reduces PTH levels. Calcitriol plasma level (reflecting previous PTH surges) can induce both calcium absorption and bone demineralization. This two-blade action is tuned by calcitonin that reduces osteoclastic bone resorption, allowing bone deposition of abundant calcium. An overnight fast with a reduced absorption of dietary calcium, might decrease plasma calcium below the regulatory set point, inducing an increase in PTH secretion. Increased average nighttime PTH secretion induces more calcitriol to be synthesized in kidneys. The resultant late calcitriol morning and daytime tide would stimulate calcium absorption from gut, or from bone, depending on the availability of dietary calcium. Due to the described time lag in calcitriol effects, increased calcium absorption might continue during daytime, regardless of the plasma calcium level. If plasma calcium is above the set point, calcitonin will allow excess calcium to deposit in bones. A speculation based on this model is that it might be more efficient to avoid calcium rich food for dinner or supper, and to administer calcium supplementation in the morning, during the calcitriol tide.

NO system dependence of atropine-induced mydriasis and L-NAME- and L-arginine-induced miosis: Reversal by the pentadecapeptide BPC 157 in rats and guinea pigs.

We revealed an immediate and hours-lasting particular NO-specific parallel miotic effect of L-NAME and L-arginine in rats and guinea pigs and a stable gastric pentadecapeptide BPC 157 157-particular effect vs. that of atropine-induced mydriasis while examining the NO system role in the normal pupils responses and pupils with atropine-induced mydriasis. We also assessed the responses to BPC 157 and its possible modulation of the changes caused by L-NAME/L-arginine and atropine. We administered locally (two drops/eye) or systemically (intraperitoneally/kg) [BPC 157 (0.4µg/eye; 10µg, 10ng, 10pg/kg), L-NAME (0.1mg/eye; 5mg/kg), and L-arginine (2mg/eye; 100mg/kg) alone and combined] at 3min prior to assessment (normal pupils) or alternatively at maximal 1% atropine-induced mydriasis (30min after two drops were administered to each eye). L-NAME/L-arginine. Normal pupil. L-NAME-miosis and L-arginine-miosis shortened and attenuated each others responses when combined (L-NAME+L-arginine) (except with guinea pigs treated locally) and were thereby NO-specific. Atropine-pupil. Both L-NAME and L-arginine counteracted atropine-induced mydriasis. With few exceptions, the atropine+L-NAME+L-arginine-animals showed a consistent shift toward the left. BPC 157. Normal pupil. Always, BPC 157 alone (both species; locally; systemically; all regimens) did not affect normal pupils. Despite specific exceptions, BPC 157 distinctively affects L-arginine-miosis (prolongation) and L-NAME-miosis (shortening). When L-arginine and L-NAME were combined (L-NAME+L-arginine+BPC 157), the effect was less pronounced. Atropine-pupil. BPC 157 alone counteracted atropine-induced mydriasis. With few exceptions (when administered with L-NAME or L-arginine or L-NAME+L-arginine), BPC 157 augments their counteracting effects. Thus, along with its l-NAME/L-arginine effects, BPC 157 participates in ocular control, potentially via NO-mediated and cholinergic mechanisms.

Analysis of biomechanical properties of patellar ligament graft and quadruple hamstring tendon graft

INTRODUCTION Two types of transplant are commonly used in the surgical management of anterior cruciate ligament lesions: the central part of the patellar ligament and quadruple tendons of the gracilis muscle and semitendinosus muscle. AIMS The aim of this study was to determine the biomechanical characteristics of patellar ligament transplants and transplants of the quadruple tendons of the hamstring muscles under tensile force in the laboratory, and to compare the results in each group of samples. MATERIALS AND METHODS The study comprised 160 specimens: 40 specimens of gracilis muscle tendons, 40 of semitendinosus muscle tendons, 40 of quadruple tendons and 40 of the patellar ligament, approximately equally distributed according to sex, age (50-70 years) and the side of the body from which the specimen had been taken. RESULTS The working curve analysis of the specimens under tensile load of a maximum force of 30N showed the least elongation (0.31%) in the quadruple tendon, followed by the gracilis muscle tendon (1.48%) and patellar ligament tendon (3.91%). CONCLUSIONS The quadruple tendon specimen showed greater strength and higher elasticity compared with the patellar ligament specimen, which proved the starting hypothesis.

High-fat diet induced changes in lumbar vertebra of the male rat offsprings

In obesity, bone marrow adiposity increases and proinflammatory cytokines excretion activates RANK/RANKL/OPG system, which leads to increased bone resorption. The aim of this study was to analyze trabecular and cortical bone parameters in animals exposed to the high-fat diet in utero and after lactation. Skeletal organ of interest was the fifth lumbar vertebra, which is not exposed to biomechanical loading in rats. Further aims were to determine TNF-α and IL-6 serum concentrations, and the intensity of the TNF-α immunohistochemical staining in the bone marrow. Ten female Sprague Dawley rats, nine weeks old, were randomly divided in two groups and fed either standard laboratory chow or food rich in saturated fatty acids during five weeks, and then mated with genetically similar male subjects. After birth and lactation male offsprings from both groups were divided in four subgroups depending on the diet they were fed until twenty-two weeks of age. The highest cholesterol and triglyceride concentration were found in both groups of offsprings fed with high-fat diet. The lowest trabecular bone volume, lowest trabecular number and highest trabecular separation were found in offsprings fed with high-fat diet of mothers on standard laboratory chow. The same group of offsprings was also characterized by the highest intensity of TNF-α immunostaining in the bone marrow and the highest TNF-α serum concentration, which suggest that this proinflammatory cytokine has interfered with bone metabolism, possibly by stimulation of bone resorption, which led to inadequate trabecular bone development and bone modeling of the fifth lumbar vertebra.

Leptin/adiponectin ratio in overweight patients – gender differences:

OBJECTIVE Obesity-related atherosclerosis is a systemic disease with a background connected to multiple metabolic-neurohumoral pathways. The leptin/adiponectin ratio has been suggested as an atherosclerotic marker in obese patients. The aim of this study was to assess (1) the significance of the L/A ratio in overweight subjects, (2) the relation with anthropometric/metabolic parameters and (3) gender difference. METHOD The study included 80 adult males and females, overweight, non-diabetic patients. Biochemical blood analysis and anthropometric and cardiovascular measurements were performed. Serum leptin levels were measured with a radioimmunoassay test and total adiponectin levels with enzyme-linked immunosorbent assay. Leptin/adiponectin ratios were calculated as ratios between total serum concentrations of leptin and adiponectin. RESULTS Differences between leptin, adiponectin serum levels and leptin/adiponectin ratios are presented in overweight persons, where females have a significantly higher leptin/adiponectin ratio than men ( p < 0.001). In men, the leptin/adiponectin ratio showed a positive correlation with total cholesterol levels ( p = 0.011), low-density lipoprotein ( p = 0.013) and triglycerides ( p = 0.032). In females, the leptin/adiponectin ratio correlated with anthropometric parameters of visceral obesity: waist circumference ( p = 0.001) and waist-to-hip ratio ( p = 0.025). CONCLUSION The leptin/adiponectin ratio could represent an atherosclerotic risk marker of the early stage of obesity. Gender plays a significant role in pathophysiological changes, with different clinical manifestations, where sex hormones have a crucial effect on neurohumoral adipose tissue activity.Objective: Obesity-related atherosclerosis is a systemic disease with a background connected to multiple metabolic-neurohumoral pathways. The leptin/adiponectin ratio has been suggested as an atherosclerotic marker in obese patients. The aim of this study was to assess (1) the significance of the L/A ratio in overweight subjects, (2) the relation with anthropometric/metabolic parameters and (3) gender difference. Method: The study included 80 adult males and females, overweight, non-diabetic patients. Biochemical blood analysis and anthropometric and cardiovascular measurements were performed. Serum leptin levels were measured with a radioimmunoassay test and total adiponectin levels with enzyme-linked immunosorbent assay. Leptin/adiponectin ratios were calculated as ratios between total serum concentrations of leptin and adiponectin. Results: Differences between leptin, adiponectin serum levels and leptin/adiponectin ratios are presented in overweight persons, where females have a significantly higher leptin/adiponectin ratio than men (p < 0.001). In men, the leptin/adiponectin ratio showed a positive correlation with total cholesterol levels (p = 0.011), low-density lipoprotein (p = 0.013) and triglycerides (p = 0.032). In females, the leptin/adiponectin ratio correlated with anthropometric parameters of visceral obesity: waist circumference (p = 0.001) and waist-to-hip ratio (p = 0.025). Conclusion: The leptin/adiponectin ratio could represent an atherosclerotic risk marker of the early stage of obesity. Gender plays a significant role in pathophysiological changes, with different clinical manifestations, where sex hormones have a crucial effect on neurohumoral adipose tissue activity.

Histological analysis of cross-sectional area of quadruple hamstring tendons and patellar ligament samples in relation to age and gender

AIMS The middle of the patellar ligament and the quadruple hamstring tendons (gracilis and semitendinosus) are two types of graft predominantly used in anterior cruciate ligament (ACL) reconstruction. The aim of this study was to determine the morphometric characteristics of patellar ligament grafts and hamstring tendon grafts and to compare the results according to subject age and gender. MATERIALS AND METHODS The study was conducted on a total of 120 samples: 40 of gracilis tendon, 40 of semitendinosus tendon and 40 of patellar ligament, distributed equally according to gender, age (50-75 years) and the side of the body from which the sample was harvested. RESULTS Morphometric and histological analyses showed that patellar ligament samples had less cross-sectional area than quadruple tendon samples (49.29 mm(2) compared with 51.46 mm(2), respectively). Sexual dimorphism was noticed in distal cross-sections of gracilis tendons (p=0.09), cross-sections of quadruple tendons (p=0.07) and patellar ligament samples (p=0.01) because of different muscular build. CONCLUSIONS All samples obtained from male subjects had larger cross-sectional areas compared with the samples taken from females. Furthermore, samples obtained from subjects aged 60 years or under had larger cross-sectional areas than samples obtained from subjects aged at least 61 years for all types of graft.

Proton pump (H+/K+-ATPase) expression in human larynx

OBJECTIVE The goal of our study was to investigate and to identify the existence of proton pump in different parts of larynx. The presence of acidic content in this area is known to be connected to several laryngeal diseases. It is mostly developed by upward recurrence of acidic gastric content, but there are some signs that the acid can be produced in the larynx as well, because of the proton pump activity in laryngeal mucosa. METHODS The study was performed on two types of specimens: (1) 50 cadaver larynges and (2) 11 surgical larynges obtained after laryngectomy. Samples were taken from supraglottis, glottis and subglottic areas and immunohistochemistry for the beta subunit of the proton pump was done. RESULTS The presence of proton pump was proved in seromucous glands in laryngeal supraglottic area, but it was also, for the first time, found in human chondrocytes in the thyroid and epiglottic cartilage. CONCLUSION These new findings could encourage further research that would illuminate better the etiopathogenesis not only of laryngopharyngeal reflux, but also the pathophysiology of cartilaginous disorders.

Effect of different combination of maternal and postnatal diet on adipose tissue morphology in male rat offspring

Abstract Purpose: Adipose tissue expansion can occur through several different ways and, under certain conditions, can be connected with chronic inflammation. TNF-α is one of the important cytokines involved in this process. Prolonged inflammation in obesity can lead to obesity-related insulin resistance and tissue dysfunction. The aim of our study was to investigate how different combination of maternal and postnatal diet affects offspring adipose tissue morphology and adipose tissue TNF-α expression. Methods: Ten female Sprague Dawley rats, 9 weeks old, were randomly divided into two groups and fed either standard laboratory chow or food rich in saturated fatty acids during 6 weeks and then mated with the same male rat. After birth and lactation male rat offspring from both groups were divided into four subgroups depending on the diet they were fed until 22 weeks old. Samples of white adipose tissue were taken from the subcutaneous, epididymal, and perirenal fat pad. On tissue sections, histomorphometric analysis was conducted using CellProfiler program v 2.1.1, and immunohistochemical staining for TNF-α was performed. Results: Greater mean surface area of subcutaneous and epididymal adipocytes was found in groups of male rat offspring with altered diet. In perirenal adipose tissue, the highest number of adipocytes was measured in the group where both mother and offspring were fed a high-fat diet. Adipocyte staining intensity for TNF-α did not differ significantly between the groups. Conclusions: Together with our previously published data, our results lead to the conclusion that alteration of postnatal diet can lead to TNF-α and adipocyte morphology changes.