Dynamics of the glycemic profile in women in long-term antiorthostatic hypokinesia

The dynamics of the glycemic curve profile was investigated in 8 healthy women during performance of the glucose tolerance test (GТТ) in 120-day antiorthostatic hypokinesia (–6°) (АNОH) simulating the effects of weightlessness. Glycemic profiles were characterized by more marked hyperglycemic response at 30 min of GТТ in the first month of stay under ANOH conditions and had a flattened appearance three months later. Glycemic profiles characteristic of delayed restoration of the blood glucose concentration appeared in the fourth month, which persisted over the first week after the end of АNОH. The glycemic profile changes developed against the background of the signs of progressive congestion of blood in the venous system of the abdominal cavity. The expansion of diameters of the main veins of the abdominal cavity was noted at the beginning of АNОH; an increase in the size of the organs and the signs of expansion of venous plexuses at the site of portocaval anastomoses, after three months; the occurrence of the signs of transudation and free fluid in the abdominal cavity was revealed at the end of hypokinesia. The countermeasures against hypodynamia did not prevent transformation of the glycemic profile nor did they influence the progression of blood flow congestion in the venous system of the abdominal cavity whose features determined the character changes in the glycemic profile in different periods of ANOH.     

REGULATION OF HAEMOPOIESIS IN ALTERED GRAVITY

(1) The aetiology of one of the most striking physiological changes occurring during space-flight, the loss of red blood cells, remains unknown, and its precise time-pattern in flight has not yet been studied. (2) It is suggested that the changes during space-flight responsible for loss of red blood cells in man are (a) loss of plasma volume resulting from disappearance of hydrostatic pressure in the circulation during weightlessness and (b) reduced energy expended in maintenance of form, posture and locomotion resulting from elimination of the usual gravitational load on the muscles. Quadrupeds, like rats, would be expected to suffer minimal blood shifts in weightlessness and therefore have an unchanged plasma volume. However, since in weightlessness the activity-related energy expenditure by the muscles is reduced, the accompanying reduced oxygen demand by the tissues would cause a reduction in erythropoietin levels and so in the production of red blood cells, and a progressive lowering of the total red blood cell mass toward a new steady-state level. (3) Loss of plasma volume alone does not explain the observed loss of red blood cells in astronauts because, in the three manned Skylab missions, as the duration of the missions increased, loss of red blood cell mass decreased, whereas loss of plasma volume increased. This discrepancy is, however, well accounted for by the above hypothesis by taking into consideration the increased level of exercise of the astronauts as the duration of the mission increased. (4) Though water submersion of human subjects does mimic the effects of weightlessness, such effects were overriden in sea mammals because of adaptation to other factors associated with a life in the sea. (5) From the presented analysis of haemopoietic changes observed in spaceflight, an experiment can be designed for a future flight to uncover the causes and mechanisms of these changes and provide a basis for developing protective measures. Thus, the space environment can be used as an investigative tool to enhance the knowledge of the function of the haemopoietic system, which is a major homeostatic system of man and other vertebrates.     

Incretion of Insulin by Pancreas and Its Inactivation in Women during Long-Term Head-down Tilt Bed Rest

An increase in insular activity in response to hyperglycemia when performing a glucose tolerance test (GTT) during normal physical activity in eight women volunteers was found to be associated with increased blood concentrations of insulin provided by an increase in secretion rate and a decrease in inactivation rate. After 81 days of stay in long-term –6° head-down tilt bed rest (bed rest), flattened glycemic curves (with low hyperglycemic lifting) observed during the GTT, what was indicated high insular activity. An increase in the insular activity was evidencing also by a smaller peak of the blood concentration of glucose from 5 min after intravenous nfusion of 20 mL of 40% glucose solution at 120 minute of the GTT. In bed rest on empty stomach no significant changes in the concentrations of insulin and C-peptide were observed. The dynamics of hormone during the GTT was showed that the appearance of flattened glycemic curves when performing GTT during bed rest was associated with more pronounced, than under the usual conditions, an increase in insulin concentration in response to hyperglycemia. An increase in the blood insulin concentration when performing GTT in bed rest was mainly provided by increased hormone secretion rate in the pancreas, but not by a decrease in its inactivation rate. If you use regular exercises for prevention of hypokinesia under conditions of bed rest, an increase in insulin concentration during GTT was mainly provided by a decrease in its inactivation rate and not by an increase in secretion rate.     

Regulation of gallbladder cholesterol concentration in the hamster. Role of hepatic cholesterol level

The goal of this investigation was to determine how alterations in hepatic cholesterol metabolism influence the cholesterol content of gallbladder bile in hamsters. Although the rate of hepatic cholesterol synthesis was varied over 600-fold, there was no direct relationship between the rate of cholesterol synthesis and the cholesterol content of gallbladder bile. However, expansion of the hepatic cholesterol pool by 42-fold resulted in an 11-fold increase in gallbladder bile cholesterol. Examination of four subfractions of the hepatic cholesterol pool revealed that the cholesterol content of gallbladder bile was most consistently correlated with the free cholesterol level in both hepatic tissue and hepatic microsomes from all experimental groups. In most groups of animals in which gallbladder bile cholesterol was increased, plasma lipoprotein cholesterol levels were also increased. It was concluded that in hamsters, under these experimental conditions, changes in the cholesterol content of gallbladder bile were directly related to alterations in cholesterol content of the liver and most closely related to alterations in the free cholesterol content of that tissue.     

Changes in fatty acid composition of thymus cells, liver, blood plasma, and muscle tissue in mice with solid Ehrlich carcinoma

The fatty acid composition of thymus cells, liver, blood plasma, muscle tissue, and tumor focus has been studied in mice with solid Ehrlich carcinoma. The tumor growth in the mice was associated with an increase in the total content of monounsaturated fatty acids in all organs and tissues studied and with a decrease in the total amount of polyunsaturated fatty acids in all tissues except blood plasma. The tumor tissue was characterized by increased levels of monounsaturated fatty acids in comparison with their levels in organs and tissues of intact animals. In the thymus of tumor-bearing mice, the contents of myristic and palmitic saturated fatty acids, which are associated with activation of the T-cell immunity, were increased. The most expressed and considerable changes in the fatty acid composition during tumor growth were observed in the muscle tissue of the animals. A possible role of changes in the fatty acid composition in the investigated organs and tissues of tumor-bearing mice in the organism’s response to tumor growth is discussed.     

Adjuvant Action of Capsular Polysaccharide of Klebsiella pneumoniae on Antibody Response

Changes in the number of cells and the weight of various lymphoid organs of mice, such as the regional lymph node (right inguinal node), spleen, thymus, bone marrow, and peripheral blood, were followed after the subcutaneous injection of the capsular polysaccharide of Klebsiella pneumoniae (CPS-K). For comparison, the changes after injection of various polyclonal lymphocyte activators (PLA) including various preparations of bacterial lipopolysaccharide (LPS) were concurrently studied. The number of cells of all of the lymphoid organs tested and that of nucleated cells in the peripheral blood decreased significantly within a few days after injection of CPS-K, and increased later. Above all, the increase in the number of cells and in the weight of the regional lymph node was most prominent (about 10 times larger than that of the normal control). Such a marked increase in the number of cells of the regional lymph node was not induced by the injection of any preparation of LPS or any other PLA tested. The initial decrease in the number of cells after CPS-K injection was most marked and long lasting in the thymus. Although LPS prepared by Westphal's method from Escherichia coli O55 or Salmonella enteritidis exhibited a stronger decreasing effect on the number of cells of the thymus, the effect of LPS prepared by Westphal's method from E. coli O111 or that by Boivin's method from E. coli O55 was similar to that of CPS-K. It is concluded therefore that CPS-K has the ability to decrease the number of cells of various lymphoid organs, especially that of the thymus, initially after injection, which is a property in common with LPS, and CPS-K has a unique ability to increase markedly the cells of various lymphoid organs, especially those of the regional lymph node, at later stages after injection. Considering that CPS-K exhibits a much stronger adjuvant effect on the antibody response than does LPS or other polyclonal lymphocyte activators, it is suggested that this extraordinarily potent activity of CPS-K in increasing the number of cells of the regional lymph node is closely related to its strong adjuvant action.     

Altered placental insulin and insulin-like growth factor-I receptors in diabetes

We have compared the characteristics of IGF-I and insulin receptors in placentas of normals and insulin dependent diabetic patients. Specific binding of both IGF-I and insulin in placental membranes from patients with good glycemic control (as reflected by blood hemoglobin content) was unaltered while that in the placental membranes from the patients with poor glycemic control was increased to approximately 20% of the normals. This observed small but significant (p less than 0.05) increase in binding of IGF-I and insulin to placental membranes from diabetic patients with poor glycemic control was further magnified, approximately twice (p less than 0.001) the normal, when the membrane receptors were purified by lectin chromatography. The kinetic analysis of IGF-I and insulin binding in both membranes and lectin purified receptors revealed that the increased binding of insulin and IGF-I to the placentas from diabetic patients with poor glycemic control was due to an approximately 2 fold increase (p less than 0.001-0.05) in the receptor numbers without any significant changes of the affinities. The molecular characteristics of the receptors in these diabetic patients, as revealed by the cross-linking studies, did not reveal any changes when compared to the normals. The parallel changes of IGF-I and insulin receptors, shown here, are in accordance with the homologous nature of these two receptors. The increased receptor numbers of these two interrelated hormones in placentas of diabetics with poor glycemic control may be relevant to the altered placental functions in diabetic pregnancy.     

Cytogenetic studies of blood lymphocytes of cosmonauts after long-ter, space flights

An analysis was performed of unstable chromosomal aberrations in peripheral blood of 36 cosmonauts after long-term space missions on "Mir" orbital station. 25 cosmonauts were examined before their flights to score spontaneous yields of cytogenetical damage. In all cases the doses absorbed by crews during space flights did not exceed permissible levels of irradiation, adopted for cosmonauts. The frequencies of chromosomal-type aberrations after space missions were found to increase significantly compared to the pre-flight levels. The yields of dicentrics and centric rings on the average were as high as 0.12 +/- 0.02 and 0.47 +/- 0.06% before and after the 1st flight, 0.18 +/- 0.05 and 0.71 +/- 0.11% before and after the 2nd flight respectively. During the inter-flight periods, usually lasted 1.5-2 years, the yields of chromosome damage lowered, but did not reach their spontaneous values. After each next flight the yields of chromosome aberrations increased again. The cytogenetical damage detected in cosmonauts' peripheral blood lymphocytes after chronic action of low doses of space radiation points out a possible increase in risks of stochastic effects in distant future for crews after long-term space missions.     

Metabolic features of cosmonauts after ballistic descent from the Earth orbit

The features of metabolic reactions in five cosmonauts after long-term flights on the International Space Station (ISS) and landing along a ballistic trajectory and in the cosmonauts returning to Earth in the mode of automatic controlled descent were studied. Venous blood samples were collected, and 50 biochemical parameter values that reflect the functional state of organs and tissues and characterize the main metabolic pathways were determined. On the first day of the recovery period after ballistic descent, the activity of the myocardial, liver, and gastrointestinal enzymes in the blood serum of cosmonauts was increased 1.3- to 2.1-fold; a number of the parameter values exceeded the upper normal limit. The level of C-reactive protein increased fivefold as compared with the preflight values. Marked signs of glycolysis, glycogenolysis and lipolysis activation as well as disorders of acid–base balance were observed. Changes in the biochemical parameter values in cosmonauts after landing along a ballistic trajectory differed significantly from those revealed in the same cosmonauts after long-term missions followed by automatic controlled descent to Earth. Negative metabolic changes tendency after landing along a ballistic trajectory remained for at least 14 days of the recovery period. It was concluded that changes in the metabolic reactions of cosmonauts after long-term missions to the ISS depend on the flights final stage conditions. After landing on Soyuz spaceships in the ballistic descent mode, the cosmonauts had adverse prognosis changes in the biochemical values characterizing the state of the cardiovascular system and marked shifts in the activity of the liver and gastrointestinal constellation enzymes. The dynamics of carbohydrate, lipid, and protein metabolism as well as acid–base balance indicates a significant tension of all body systems and exhaustion of its functional reserves.     

Analysis and Evaluation of the Functional State of the Cardiovascular System in Cosmonauts during Long-term Spaceflights

Forty-four cosmonauts participating in 28 main long-term (73–438 days) missions on the Mirorbital station performed functional tests with graded physical exercise using a bicycle ergometer. There were two types of this functional load. The cosmonauts that participated in the first eight main missions performed a two-step exercise with a total load power of 1150 W. In the remaining cosmonauts, the exercise was three-step, with a total power of 1350 W. The results obtained during the flight were compared with the results of the same tests performed before the flight, which served as control values for each cosmonaut. To estimate the load tolerance, the heart rate (HR), systolic blood pressure, stroke volume (SV), cardiac output (CO), and cardiac index were analyzed. The data were grouped according to the load, taking into account the type of blood circulation for each group before and during the flight. The ratio between different types of blood circulation was found to change during the flight. The responses to both types of exercises before the flight were less favorable in the cases of the hyperkinetic type of circulation. In these cases, the dominance of the chronotropic function of the heart determined the increase in CO. In the cases of the hypo- and eukinetic types of circulation, the response to the exercise was close to normotonic. In microgravity, irrespective of the circulation type and the exercise, the mechanism of the CO formation changed: the effect of HR was dominant, and there was no increase in SV. Insufficient venous return to the chambers of the heart is the main cause of the decreased response of SV to exercises during spaceflight.     

Primary carcinoma of the gallbladder; review of 173 cases

One hundred seventy-three cases of primary carcinoma of the gallbladder were analyzed. In the group studied they made 2.11 per cent of all malignant tumors found at autopsy and were found in 1.89 per cent of all cases in which operation was done on the biliary tract. There was no appreciable change in the incidence of this tumor at autopsy during the period studied (1918-1948) at the Los Angeles County Hospital. Sixty-eight per cent of the cases were in females. A particularly high incidence was noted in Mexican females. Upper abdominal pain, loss of weight, nausea and vomiting, jaundice, and palpable mass or enlarged liver were the most common clinical features. Approximately one-third of the patients in whom the lesion was found at operation and one-fifth of all the patients whose records were studied had a history of chronic gallbladder disease. All but two of the 38 patients operated on were dead or had clinical recurrence within two years. One was alive and well 12 years after cholecystectomy. The most common gross appearance, particularly at autopsy, was a large tumor mass replacing the gallbladder and radiating to nearby organs, particularly the liver. In about one-third of the cases the tumor was grossly limited to the gallbladder. Polypoid tumors occurred in only about 10 per cent of the cases and most of the tumors were diffusely growing adenocarcinoma. Perforation appeared in nine cases, usually with fistula to the gastrointestinal tract. All of the tumors were histologically adenocarcinoma, usually of simple glandular structure. No purely squamous cell growth occurred. Gallstones were found in 79.8 per cent of the cases.     

PRIMARY CARCINOMA OF THE GALLBLADDER—Review of 173 Cases

One hundred seventy-three cases of primary carcinoma of the gallbladder were analyzed. In the group studied they made 2.11 per cent of all malignant tumors found at autopsy and were found in 1.89 per cent of all cases in which operation was done on the biliary tract. There was no appreciable change in the incidence of this tumor at autopsy during the period studied (1918-1948) at the Los Angeles County Hospital. Sixty-eight per cent of the cases were in females. A particularly high incidence was noted in Mexican females.Upper abdominal pain, loss of weight, nausea and vomiting, jaundice, and palpable mass or enlarged liver were the most common clinical features. Approximately one-third of the patients in whom the lesion was found at operation and one-fifth of all the patients whose records were studied had a history of chronic gallbladder disease.All but two of the 38 patients operated on were dead or had clinical recurrence within two years. One was alive and well 12 years after cholecystectomy.The most common gross appearance, particularly at autopsy, was a large tumor mass replacing the gallbladder and radiating to nearby organs, particularly the liver. In about one-third of the cases the tumor was grossly limited to the gallbladder. Polypoid tumors occurred in only about 10 per cent of the cases and most of the tumors were diffusely growing adenocarcinoma. Perforation appeared in nine cases, usually with fistula to the gastrointestinal tract. All of the tumors were histologically adenocarcinoma, usually of simple glandular structure. No purely squamous cell growth occurred.Gallstones were found in 79.8 per cent of the cases.     

A low‐glycemic diet lifestyle intervention improves fat utilization during exercise in older obese humans

Objective: To determine the influence of dietary glycemic index on exercise training‐induced adaptations in substrate oxidation in obesity. Design and Methods: Twenty older, obese individuals undertook 3 months of fully supervised aerobic exercise and were randomized to low‐ (LoGIX) or high‐glycemic (HiGIX) diets. Changes in indirect calorimetry (VO₂; VCO₂) were assessed at rest, during a hyperinsulinemic‐euglycemic clamp, and during submaximal exercise (walking: 65% VO₂max, 200 kcal energy expenditure). Intramyocellular lipid (IMCL) was measured by ¹H‐magnetic resonance spectroscopy. Results: Weight loss (?8.6 ± 1.1%) and improvements (P < 0.05) in VO₂max, glycemic control, fasting lipemia, and metabolic flexibility were similar for both LoGIX and HiGIX groups. During submaximal exercise, energy expenditure was higher following the intervention (P < 0.01) in both groups. Respiratory exchange ratio during exercise was unchanged in the LoGIX group but increased in the HiGIX group (P < 0.05). However, fat oxidation during exercise expressed in relation to changes in body weight was increased in the LoGIX group (+10.6 ± 3.6%; P < 0.05). Fasting IMCL was unchanged, however, extramyocellular lipid was reduced (P < 0.05) after LoGIX. Conclusions: A LoGIX/exercise weight‐loss intervention increased fat utilization during exercise independent of changes in energy expenditure. This highlights the potential therapeutic value of low‐glycemic foods for reversing metabolic defects in obesity.     

Cardiovascular Vagosympathetic Activity in Rats with Ventromedial Hypothalamic Obesity

Objective: Rats with ventromedial hypothalamic lesion (VMH) are massively obese with endogenous hyperinsulinemia, insulin resistance, low sympathetic activity, and high parasympathetic activity, which are likely to induce hypertension. The goal was to follow in this model the long‐term hemodynamic changes and to investigate the role of autonomic nervous system and insulin resistance in these changes. Research Metho ds and Procedures: Heart rate and blood pressure were monitored for 12 weeks after operation using a telemetric system in VMH and sham rats. Plasma catecholamines and heart β‐adrenoceptors were measured. Glucose tolerance was studied after an intravenous glucose injection and insulin sensitivity during a euglycemic hyperinsulinemic clamp test. Results: A marked bradycardia and only a mild increase in blood pressure occurred in VMH rats compared with sham animals. Response to autonomic‐acting drugs showed an increase in heart vagal tone and responsiveness to a β‐agonist drug. Plasma catecholamine levels were markedly increased, and the density and affinity of heart β‐adrenoceptors were similar in VMH, sham, and control rats. Muscle glucose use was reduced by 1 week after operation in VMH animals. Discussion: These results show the following in this model of massively obese rats with sympathetic impairment: 1) adrenal medulla secretion is increased, probably as a result of hyperinsulinemia and increased vagal activity; 2) cardiac responsiveness to β‐agonist stimulation is increased; and 3) despite these changes and suspected resistance to the vasodilative effect of insulin, blood pressure does not increase. We conclude that high vagal activity may be protective against hypertension associated with obesity.     

Reproductive organs regulate leaf nitrogen metabolism mediated by cytokinin signal

The metabolism of vegetative organs in plants changes during the development of the reproductive organs. The regulation of this metabolism is important in the control of crop productivity. However, the complexity of the regulatory systems makes it difficult to elucidate their mechanisms. To examine these mechanisms, we constructed model experiments using Arabidopsis to analyze metabolic and gene expression changes during leaf-stage progression and after removal of the reproductive organs. Leaf gene expression levels and content of major amino acids, both of which decreased during leaf-stage progression, increased after removal of the reproductive organs. In particular, the levels of expression of cytokinin biosynthesis genes and cytokinin-responsive genes and the cytokinin content increased after removal of the reproductive organs. Analysis of plants with knockout of a cytokinin-biosynthetic gene (AtIPT3) and a cytokinin receptor gene (AHK3) indicated that glutamate dehydrogenase genes (GDH3) were regulated by cytokinin signaling. These data suggest that cytokinins regulate communication between reproductive and vegetative organs, and that GDH3 is one target of the cytokinin-mediated regulation of nitrogen metabolism. Electronic supplementary material  The online version of this article (doi:) contains supplementary material, which is available to authorized users.     

Changes in the Levels of Dolichol and Dolichyl Phosphate in a Murine Model of Niemann-Pick''s Type C Disease

Abstract: The distributions of mevalonate pathway lipids in various organs of a mouse strain used as a model for Niemann-Pick's type C disease were analyzed. Extensive accumulation of cholesterol was observed in all tissues with the exception of the brain, where the content of this lipid was decreased. The changes in total dolichol contents of most organs varied from a 50% decrease in the lung to a twofold increase in kidney and heart. There was relative enrichment of longer-chain dolichols, but no increase in the relative amount of α-unsaturated polyprenols was observed. The levels of dolichyl phosphate in all organs were increased, and most of this lipid was associated with bound oligosaccharides or proteins. Ubiquinone levels were largely unchanged. Subfractionation studies revealed that heavy and light lysosomes exhibited a 10-fold increase in cholesterol level, the amount of dolichol was decreased in lysosomes and increased in microsomes, and there was an increase in the dolichyl phosphate levels of all three of these subfractions. These results indicate that in diseased mice cholesterol accumulation in various organs is paralleled by an increase in the dolichyl phosphate concentration, whereas dolichol transport from the endoplasmic reticulum to lysosomes is inhibited.     

Changes in serum lysozyme activity in terminal states caused by blood loss]

A study was made of the dynamics of the lysozyme activity of the serum in dogs which sustained clinical death on the background of a 2-hour hypovolemic hypotension due to blood loss. There was revealed a progressive increase in the lysozyme activity of the serum during the hypotension and during the first 30 minutes of the postreanimation period. Lysozyme activity of the serum was increased in the course of 4 days after the revival. The significance of the lysozyme activity of the serum as an index of hypoxic injury of the internal organs in terminal conditions is discussed.     

Foetal circulatory responses to arrest of uterine blood flow in sheep: effects of chemical sympathectomy.

Acute foetal asphyxia, caused by arrest of uterine blood flow, increases both sympathetic activity and peripheral vascular resistance and decreases blood flow to peripheral organs (Jensen et al., J. Dev. Physiol., 9, 543-559). The rapidity and uniformity of this peripheral vasoconstriction suggest that the sympatho-neuronal system may reflexly cause these initial blood flow changes during acute asphyxia. To test this hypothesis, we studied 5 intact and 6 chemically sympathectomized (6-hydroxy-dopamine, 46.1 +/- 6 mg/kg foetal weight) chronically prepared normoxaemic foetal sheep in utero at 0.9 of gestation. Organ blood flows (microsphere method), plasma concentrations of catecholamines, vasopressin, and angiotensin II, acid-base balance and blood gases were measured before, during and after arrest of uterine blood flow for 2 min, i.e., at 0, 1, 2, 3, 4 & 30 min. In intact foetuses there was a progressive increase in arterial blood pressure and a rapid circulatory centralization in favour of the brain stem and heart and at the expense of most of the peripheral organs. The changes in peripheral blood flow during and after asphyxia were well reflected by those in the skin and scalp. In chemically sympathectomized foetuses, arterial blood pressure fell transiently at 1 min of asphyxia and cardiac output was redistributed towards the carcass and intestinal organs at the expense of the heart, spinal medulla, and placenta. We conclude that in foetal sheep at 0.9 of gestation, the short-term adaptation to arrest of uterine blood flow is a rapid and profound peripheral vasoconstriction to effect an increase in arterial blood pressure. This initial response during circulatory centralization, which is necessary to increase or maintain blood flow to the heart, brain stem, and placenta, is blunted by sympathectomy. Thus, the foetal sympatho-neuronal system is important for short-term adaptation to and intact survival of asphyxia.     

Human gallbladder carcinoma: Role of neurotrophins,MIB-1, CD34 and CA15-3

Gallbladder carcinoma is the most common biliary tract tumor and the fifth most common gastrointestinal tract cancer. The prognosis of gallbladder carcinoma is poor and less than 5% of the patients are still alive five years postoperatively. Gallbladder specimens were obtained during surgical operations performed in eleven patients for resection of a gallbladder carcinoma, and during five autopsies (control cases selected among patients who died from for other causes, excluding those suffering from biliary or hepatic diseases). Immunohistochemical characterization and distribution of neurotrophins, with their respective receptors, were analyzed. The actual role played by these neurotrophic factors in the general regulation, vascular permeability, algic responsiveness, release of locally active substances and potential tumorigenesis in the gallbladder and biliary ducts compartment remains controversial. Our study revealed an increased immunohistochemical expression of NGF and TrKA in the epithelium and in the epithelial glands of the gallbladder carcinoma together with an evident immunoreactivity for BDNF in the same neoplastic areas. An evident immunoreactivity for NGF, TrKA and BDNF was observed in control specimens of gallbladder obtained during autopsies, whereas a weak or quite absent immunoreactivity was observed in the same specimens for NT4, TrKC and p75. On the contrary an appreciable immunoreactivity for p75 was observed in the specimens harvested from patients with gallbladder carcinoma. We also investigated the expression of some known tumor markers such as MIB-1 (anti Ki-67), CD34 and CA15-3, to identify a possible correlation between the expression of these molecular factors and the prognosis of gallbladder carcinoma. They resulted highly expressed in the stroma (CD34 and CA 15-3) and in the epithelium/epithelial glands (MIB-1) of the neoplastic areas and appeared to be almost absent in the control cases, suggesting that these markers, taken together, could be adopted as a panel of prognostic factors in the evaluation of the gallbladder carcinoma.Key words: neurotrophins, human biliary ducts, gallbladder, immunohistochemistry, cholangiocarcinoma.     

Females of the marine amphipod Jassa marmorata mate multiple times with the same or different males

Cardiovascular and respiratory variables were recorded in the blue crab, Callinectes sapidus, during injury and subsequent autotomy of a chela. Cardiac function and haemolymph flow rates were measured using a pulsed-Doppler flowmeter. Oxygen uptake was recorded using an intermittent flow respirometry system. Crabs reacted to the loss of a chela with a rapid increase in heart rate, which was sustained for 2?h. Stroke volume of the heart also increased after the chela was autotomized. A combined increase in heart rate and stroke volume led to an increase in cardiac output, which was maintained for an hour after the loss of a chela. There was also differential haemolymph perfusion of various structures. There was no change in perfusion of the anterolateral arteries or posterior and anterior aortae, during injury of the chela or subsequent autotomy. Haemolymph flow rates did increase significantly through the sternal artery during injury and immediately following autotomy of the chela. This was at the expense of blood flow to the digestive gland: a sustained decrease in haemolymph flow through the hepatic arteries occurred for 3?h following autotomy. Fine-scale cardiac changes associated with the act of autotomy included a bradycardia and/or associated cardiac pausing before the chela was shed, followed by a subsequent increase in cardiac parameters. Changes in the cardiovascular physiology were paralleled by an increase in oxygen uptake, which was driven by an increased ventilation of the branchial chambers. Although limb loss is a major event, it appears that only acute changes in physiology occur. These may benefit the individual, allowing rapid escape following autotomy with a subsequent return to normal activity.