Biomedical subjects

G Varga

Publications and source records attributed to G Varga.

At least 55 records · Page 3Linked to original sources

PubMed1998

Different actions of CCK on pancreatic and gastric growth in the rat: effect of CCK(A) receptor blockade.

1. It is now well established that cholecystokinin (CCK) has a major physiological role in the regulation of pancreatic secretion and gastro-intestinal (GI) motility. Both these actions are mediated by stimulation of CCK(A)-receptors located on pancreatic acini and GI smooth muscle cells. While chronic administration of CCK-like peptides invariably causes pancreatic hypertrophy and hyperplasia, their action on gastric growth remains controversial. 2. In the present investigation the action of exogenous and endogenous CCK on both pancreatic and gastric growth was studied in the same animal. In addition, the ability of dexloxiglumide, a new potent and selective CCK(A)-receptor antagonist, to counteract CCK-mediated effects was evaluated. 3. The amphibian peptide caerulein (1 microg kg(-1) intraperitoneally three times daily) was used as a CCK agonist, while camostate (200 mg kg(-1) intragastrically once daily), a synthetic protease inhibitor, was used to release endogenous CCK. They were administered to rats for seven days with or without dexloxiglumide (25 mg kg(-1) subcutaneously 15 min before the stimulus). On the eighth day, animals were killed, the pancreas and stomach excised, weighed, homogenized and their protein and DNA content measured. 4. Both exogenous and endogenous CCK increased the weight of the pancreas as well as the total pancreatic protein and DNA content. Dexloxiglumide, which alone did not affect pancreatic size and composition, was able to counteract both caerulein- and camostate-induced pancreatic changes. Neither stimuli affected gastric growth in respect of weight and composition of the oxyntic gland area and the antrum. 5. These results show different effects of CCK on pancreatic and gastric growth. The CCK-induced pancreatic hypertrophy and hyperplasia are blocked by the potent and specific CCK(A)-receptor antagonist, dexloxiglumide. This compound therefore represents a useful tool to investigate CCK-receptor interactions in peripheral organs.

Animals↗

PubMed1998

Agonists and antagonists of regulatory peptides as tools to study regulation of pancreatic exocrine secretion, cell proliferation and gene expression.

For more than two decades, our research group has been studying the pancreatic actions of three groups of regulatory peptides: members of the cholecystokinin/gastrin family, bombesin-like peptides and somatostatin. Investigating these peptides, our work has focused on three particularly interesting aspects: peptidergic regulation of pancreatic enzyme secretion and growth in adult rats, peptidergic control of pancreatic enzyme secretion and growth during postnatal development in rats, and peptidergic regulation of proliferation and differential gene expression in pancreatic adenocarcinoma cells. Our data confirmed that the control of the exocrine function of the pancreas is complex, and that it involves peptides such as the cholecystokinin/gastrin-like peptides, bombesin-like peptides and somatostatin. In these investigations, it became evident that selective peptide receptor agonists, antagonists and monoclonal antibodies raised against peptides are useful tools to identify the role of these bioactive peptides in pancreatic exocrine secretion and cell proliferation.

Adenocarcinoma↗

PubMed1998

Crohn's disease presenting as pyogenic liver abscess with review of previous case reports.

A 40-yr-old male doctor from India presented with pyogenic liver abscesses as the first manifestation of Crohn's disease. The Crohn's disease itself was limited to the appendix and the adjacent cecum and could be diagnosed only 6 months after the presentation with liver abscess. This single case highlights three unusual features of Crohn's disease, and stresses the importance of meticulous search for a cause for pyogenic liver abscess when it occurs in an otherwise healthy adult.

Adult↗

PubMed1997

Cloning of novel transcripts of the human guanine-nucleotide-exchange factor Mss4: in situ chromosomal mapping and expression in pancreatic cancer.

In a previous large-scale analysis of gene expression in pancreatic cancer using gridded arrays of cDNA libraries and differential hybridizations, a gene that was a homolog to human mss4 was identified. Mss4 is a guanine-nucleotide-exchange factor for the Sec4/ Ypt1/Rab family of small GTP-binding proteins involved in the regulation of intracellular vesicular transport. By fluorescence in situ hybridization the human mss4 gene was assigned to chromosome 1q32-q41. Northern blot analysis revealed that three mss4 mRNA species are transcribed in human tissues of 780, 1200, and 2800 bp in length, respectively. Cloning and sequencing of the human mss4 transcripts from a pancreatic cancer cDNA library revealed that these mRNA species differ in the length of the 3-untranslated region and are probably due to the alternate use of polyadenylation sites. All mRNA species were detected at moderate to high levels in pancreatic cancer cell lines and were overexpressed in pancreatic cancer tissue compared to both normal pancreas and chronic pancreatitis tissue. However, the 1200-bp transcript was the Mss4 mRNA species with the highest level of expression in more than 50% of tumor cells and tissues. High levels of expression were found as well in other human tumor tissues. Mss4 as guanine-exchange factor required in the regulation of intracellular transport may be of importance for the function and growth of human tumor cells. However, the precise role of mss4 in human tumor cells is unknown and remains to be elucidated.

Amino Acid Sequence↗

PubMed1997

Cloning of a gene highly overexpressed in cancer coding for a novel KH-domain containing protein.

In a previous large scale screen for differentially expressed genes in pancreatic cancer, we identified a gene highly overexpressed in cancer encoding a novel protein with four K-homologous (KH) domains. KH-domains are found in a subset of RNA-binding proteins, including pre-mRNA-binding (hnRNP) K protein and the fragile X mental retardation gene product (FMR1). By fluorescence in situ hybridization (FISH) the identified gene named koc (KH domain containing protein overexpressed in cancer) was assigned to chromosome 7p11.5. Two pseudogenes were localised on chromosome 6 and 11. The cloned koc cDNA has a 250 bp 5'-UTR, a 1740 bp ORF and a 2168 bp 3'-UTR. The AU-rich 3'-untranslated region of koc contains eight AUUUA and four AUUUUUA reiterated motifs. The deduced koc protein with 580 amino-acids has a relative molecular mass (Mr) of approximately 65,000 (65 K). The koc transcript is highly overexpressed in pancreatic cancer cell lines and in pancreatic cancer tissue as compared to both, normal pancreas and chronic pancreatitis tissue. High levels of expression were as well found in tissue samples of other human tumours. As the KH domain has been shown to be involved in the regulation of RNA synthesis and metabolism, we speculate that koc may assume a role in the regulation of tumour cell proliferation by interfering with transcriptional and or posttranscriptional processes. However, the precise role of koc in human tumour cells is unknown and remains to be elucidated.

Amino Acid Sequence↗

PubMed1997

Inflammatory mediators and surgical trauma regarding laparoscopic access: free radical mediated reactions.

In this prospective study the free radical mediated reactions, the changes of endogenous antioxidant defense mechanism and activation of leukocytes were measured from the blood of patients undergoing elective cholecystectomy because of symptomatic cholecystolithiasis. The patients were randomised into two groups. Group one contained 21 patients treated by open cholecystectomy(OC). Group two consisted of 21 patients treated by laparoscopic cholecystectomy (LC). Both groups had similar patient characteristics. Patients with acute cholecystitis, pancreatitis, choledocholithiasis or other disease were excluded. Values from patients in both groups were compared. The measured biochemical parameters are the following: malondialdehyde (MDA) as a marker of the free radical induced lipid peroxidations, reduced and oxidised glutathione (GSH-GSSG), as endogenous scavengers as well as markers of oxidative stress and myeloperoxidase activity (MPO) of leukocytes. The results showed significantly lower values of postoperatively measured MDA, GSH-GSSG, and MPO activity of leukocytes in patients with laparoscopic cholecystectomy, indicating a lesser stress response and tissue trauma in this group of patients. The results correspond to the favourable results of most other trials evaluating clinical aspect of LC.

Antioxidants↗

PubMed1997

Inflammatory mediators and surgical trauma regarding laparoscopic access: acute phase response.

Numerous studies have tried to compare different aspects of patient response to laparoscopic cholecystectomy (LC) versus open cholecystectomy (OC). Our study focused on the acute phase response in order to clarify the better patient recovery following LC. Sixteen patients scheduled for elective cholecystectomy were equally allocated into groups of OC and LC. Blood samples were collected before and for four days after the procedures. Levels of interleukin 6 (IL-6) and C-reactive protein (CRP) were determined by ELISA technique. IL-6 value increased ten fold on the first postoperative day (52.8 pg/ml) in the OC group with a return to baseline value by the fourth postoperative day. In contrast a moderate increase postoperatively (12.1 pg/ml) with a fast normalisation of IL-6 value by the second postoperative day was noted in LC group. A similar pattern was observed in the CRP level. CRP peaked to 84.1 mg/l by the second follow-up day after OC, while only an insignificant rise to 52.7 mg/l was registered in the LC group with again a faster return to baseline value. The marked contrast between the two groups with regard to IL-6 and CRP changes clearly underlines a diminished acute phase response following LC, which verifies LC as probably a less traumatic procedure.

Acute-Phase Reaction↗

PubMed1997

Cardioprotection during heart ischemia-reperfusion.

Oxygen reactive species play a significant role in reperfusion tissue damages. In this study we aimed to investigate the mechanisms of injury regarding changes of neutrophil function. In our experiments the left descending coronary artery (LAD) was ligated in Beagle dogs for 1 hour followed by one hour reperfusion. Animals were divided into two groups: Group I. dogs (n = 10) served as control: Group II. the animals (n = 10) were treated by cardioprotective drug Bisaramil. Peripheral blood samples were taken for neutrophil isolation before operation and subsequent reperfusion (5 min, 1 hour). The stimulated superoxide radical generating capacity of polymorphonuclear leukocytes (PMN) was measured. The lipid peroxidation (MDA), amount of reduced glutathione (GSH) and activity of superoxide dismutase (SOD) were measured in non-ischemic and ischemic parts of left ventricle. There was no significant changes either in control or in treated animals in respect to changes of neutrophil radical production after one hour LAD ligature, however there was a significant discrepancy (p < 0.001) between control and treated animals following a 1 hour reperfusion. The values of MDA in the ischemic-area increased characteristically in the Group I. parallel with decrease of scavenger GSH and SOD. In contrast in Group II., where depleted PMN radical production was observed endogenous scavengers were preserved on a higher level. In summary we can conclude that diminished superoxide radical production of circulating neutrophils during reperfusion has beneficial effects on tissue injury caused especially by free radicals.

Animals↗

PubMed1997

Inflammatory mediators and surgical trauma regarding laparoscopic access: neutrophil function.

Polymorphonuclear leukocytes (PMN) are well recognised as being the principal cells in the inflammatory response reaction. The current investigation was designed to evaluate the stimulated state of neutrophils in patients undergoing open (OC) and laparoscopic cholecystectomy (LC). The superoxide radical generation of isolated PMN and its lag time, and PMN elastase were measured in peripheral venous blood samples collected from 42 patients. The observation period started on the day of hospital admission and ended on the 5 th day. Our results showed that although there were no characteristic changes in the superoxide radical production of PMN in the LC group, we found a marked depletion already by the first day in OC group which persisted during the whole observation period. There was an elevation of PMN elastase on the first postoperative day in both groups, but in the laparoscopically operated patients it decreased considerably on the 3rd postoperative day while in the OC group it maintained a high level. The same discrepancy was present between the two groups on the 5th day. Decreased free radical production of isolated PMN may reflect depleted neutrophil functional state, while changes of PMN elastase indicates increased harmful potential. These data suggest the differences in neutrophil activation between the two groups can be partially responsible for the better outcome in patients operated by laparoscopic cholecystectomy.

Acute-Phase Reaction↗

PubMed1997

Postoperative chemoembolism treatment of primary and metastatic malignant hepatic tumours.

Between 1992 and 1996 62 patients were operated for primary malignant and metastatic hepatic tumours. After the operation 31 patients received cytostatical treatment, 9 patients were treated with the method of chemoembolism. 46 patients are alive 30.7 (5-54) months after the operation. 9 patients died 12.5 (3-27) months after the resection of the liver. Authors have favourable experiences on the treatment of chemoembolism.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed1996

Camostate- and caerulein-induced delay of gastric emptying in the rat: effect of CCK receptor antagonists.

The effect of camostate, a potent releaser of endogenous cholecystokinin (CCK), and of caerulein, an amphibian peptide mimicking the biological actions of CCK, as well as of selective CCK receptor antagonists on gastric emptying of liquids was studied in the rat. Oral administration of camostate (200 mg/kg with the liquid test meal preceded by the same dose 10 min before the meal) significantly delayed gastric emptying of saline, an effect which was completely blocked by previous administration of the CCKA receptor antagonist, devazepide, at a dose (1 mg/kg i.v.) unable to modify the emptying rate when administered alone. Caerulein (0.03-30 nmol/kg i.v.) also delayed the emptying rate in a dose-dependent manner, with an ID50 of 3.94 nmol/kg. The effect of the peptide was also inhibited by devazepide. The CCKB receptor antagonist, L365,260 (3R-(+)-N-(2,3-dihydro-1-methyl-2-oxo-5-phenyl-1H-1, 4-benzodiazepine-3-yl)-N'-(3-methylphenyl)-urea; 3 mg/kg i.v.), was completely unable to modify the CCK (both endogenous and exogenous)-induced delay in gastric emptying. Repeated (7 days) camostate administration did not modify the gastric motor response to endogenous CCK, thus, suggesting that adaptation did not take place. These results demonstrate that endogenous and exogenous CCK delays gastric emptying of liquids through stimulation of CCKA receptors and suggest that adaptation of the gastric motor response to CCK does not occur.

Analysis of Variance↗

PubMed1996

Non-adrenergic non-cholinergic neuron stimulation in the cat lower esophageal sphincter.

Both electrical field stimulation and nicotine produced non-adrenergic non-cholinergic (NANC) relaxation of the circular muscle strips from the cat lower esophageal sphincter in the presence of 5 microM guanethidine and 5 microM scopolamine. Low-frequency stimulation (2 Hz, 0.2 ms duration, supramaximal current intensity, 20-s train) provoked a transient relaxation, while at high-frequency stimulation (20 Hz) a slow restoration to the resting tone was observed. Blockade of nitric oxide (NO) synthesis by 1 mM N omega -nitro-L-arginine decreased by 20% the amplitude of the 20 Hz-induced relaxation and changed the pattern of relaxation, making it similar to the sustained relaxation evoked by exogenously applied vasoactive intestinal peptide (VIP). After chymotrypsin (4 U/ml), the pattern of the high-frequency-induced relaxation resembled that of the low-frequency-induced relaxation. Similarly, chymotrypsin changed the shape of nicotine-provoked relaxation, increasing the speed of restoration to the resting tone. We suggest that the fast relaxation elicited in cat lower esophageal sphincter by electrical field stimulation or nicotine is initiated by NO. The slow restoration to the resting tone in the case of high-frequency- or nicotine-induced relaxation seems to be due to the release of VIP or VIP-like peptides. The possibility of participation of another transmitter(s) involved in NANC relaxation should not be excluded.

Animals↗

PubMed1996

[Critical evaluation of factors influencing pancreatic cytoprotection].

The authors give a brief survey on adaptive pancreatic cytoprotection and vasoprotection in the framework of which noxious agents and factors of defensive mechanism are made known and critically evaluated. In development of acute pancreatitis intraacinar redistribution of lysosomal hydrolases, colocalization of digestive and lysosomal enzymes, escape of digestive and lysosomal enzymes from pancreatic ductal system into the interstitium, inflammatory modulators released from macrophages and evoking local inflammation, ischaemia, furthermore feedback regulation of pancreatic secretion can be regarded as motives. Factors of defensive mechanism include prostaglandins, nitric oxide and the unobstructed, juice flow which promote the repair of injured membranes in acinar and vascular endothelial cells, respectively. Their whole sum may be called adaptive pancreatic cyto- and vasoprotection or pancreatic "self-defence mechanism".

Acute Disease↗

PubMed1996

Age-dependent influence of octreotide on stimulated pancreatic growth in the postnatal period of rats.

OBJECTIVE: To investigate the effect of long-acting octreotide (SMS 201-995) on the plasma growth hormone level in preweaning rats and to study the growth and composition of the exocrine pancreas in these rats after stimulation by caerulein- and camostate-induced endogenous cholecystokinin (CCK). METHODS: Wistar rats of both sexes were treated as littermate pairs in two periods of postnatal age, from days 1 to 11 and from days 11 to 21. To stimulate pancreatic growth, caerulein (3 micrograms/kg subcutaneously three times daily) was given from days 1 to 11, and oral camostate (200 mg/kg given once daily) or CCK-8 (10 micrograms/kg subcutaneously three times daily) was administered from days 11 to 21. Octreotide (6 or 15 micrograms/kg subcutaneously twice daily) was administered alone or in combination with caerulein or camostate. The rats were exsanguinated on days 11 or 21, and each pancreas was removed, weighed and analysed. RESULTS: Caerulein stimulated pancreatic growth and raised the trypsin concentration; camostate induced pancreatic hypertrophy and hyperplasia. By day 11, octreotide had decreased the plasma growth hormone level and the basal pancreatic trypsin concentration and content. Given in combination with caerulein, octreotide reduced the growth hormone level and the stimulated trypsin and DNA contents. By day 21, rats treated with octreotide in the camostate group showed a reduced basal pancreatic trypsin concentration and a decreased basal trypsin content (although the changes were not significant). Plasma growth hormone levels were not significantly reduced. CONCLUSION: The antitrophic pancreatic action of octreotide and its plasma growth hormone-lowering effect were shown in rats during the first 10 days after birth. These effects were less notable from days 11 to 21, a period when CCK receptors increase in number and components of the stimulus-secretion mechanism are mature.

Analysis of Variance↗

PubMed1996

Effect of dexloxiglumide and spiroglumide, two new CCK-receptor antagonists, on gastric emptying and secretion in the rat: evaluation of their receptor selectivity in vivo.

BACKGROUND: Clear definition of the role of CCK in the physiology of gastric motor activity has been long hampered by the lack of specific and potent nonpeptide antagonists of CCK-receptors. The availability of such compounds has stimulated a broad array of investigations into the physiological actions of this hormone and to examine its putative role in certain diseases. AIMS: The effect of two recently developed CCK-receptor antagonists, namely dexloxiglumide and spiroglumide, on gastric emptying and secretion as well as their selectivity towards CCKA- and CCKB-receptors in vivo was studied in the rat. METHODS: Gastric emptying was quantified by using a liquid noncaloric meal labelled with phenol red. Acid secretion was measured by titration in conscious rats. RESULTS: The putative CCKA-antagonist, dexloxiglumide, administered by intravenous route, was able to inhibit CCK-8-induced delay of gastric emptying in a dose-dependent fashion, with an ID50 (95% CL) of 1.14 (0.84-1.53) mg/kg. Similarly, the putative CCKB-gastrin-antagonist, spiroglumide, proved to be capable of inhibiting dose-dependently pentagastrin-induced acid hypersecretion, its ID50 being 20.1 (8.67-46.4) mg/kg. On the other hand, dexloxiglumide, at doses able to almost completely block CCKA mediated effects (i.e. delay of gastric emptying), was ineffective against pentagastrin-induced acid hypersecretion. Similarly, spiroglumide, at doses which inhibit by 55% CCKB-gastrin mediated effects (i.e. acid secretion) was inactive when tested against CCK-8 induced delay of gastric emptying. CONCLUSIONS: These results demonstrate in vivo that dexloxiglumide is a selective antagonist for CCKA-receptors whereas spiroglumide is selective for CCKB-gastrin-receptors. These compounds are therefore useful tools for discriminating between different subclasses of CCK-receptors in vivo and might have a therapeutic potential in motility or acid-related disorders.

Animals↗

PubMed1995

Distinct receptors mediate gastrin-releasing peptide and neuromedin beta-induced delay of gastric of liquids in rats.

The present study was carried out to define which bombesin receptors are involved in the delay of gastric emptying induced by bombesin-like peptides. Adult male rats were fitted with gastric and jugular vein cannulas. Gastric emptying was determined 5 min after a 3-ml intragastric load of 0.9 M NaCl using phenol red as a marker. Mammalian bombesin-like peptides gastrin-releasing peptide-10 and neuromedin B both induced a delay of gastric emptying. When [Phe6]bombesin-(6-13)-methyl ester, a selective antagonist of the gastrin-releasing peptide-preferring subtype of bombesin receptors, was injected 5 min before the agonists, the effect of gastrin-releasing peptide-10 was competitively inhibited, whereas that of neuromedin B remained unaffected. Our results indicate that gastrin-releasing peptide-10 and neuromedin B delay gastric emptying by acting on distinct receptors in rats, in vivo.

Animals↗

PubMed1995

Revelations from a meta database system on environmental health problems.

Harmful effects of environmental pollution to the health status of population is well-known to ecologists and experts on health sciences. However, prevention and protection against such direct environmental hazards to save, or, in a worse case, re-establish the ecological balance are anything but successful. It is true, even if modern monitoring and measuring technology, adequate information systems, and related data bases are available. Precision of measurements and surveys, assessment and evaluation of the relationship between component elements of negative environmental effects on one the one hand, and general health conditions of the population on the other, could be increased by applying methods of informatics i.e., if we carry out a preliminary and professional analysis of the already existing information property. A useful tool for such activities could be the creation and maintenance of an integrated meta-type data base. It is a set sorted by a causal relations group of information that is collected from several databases of different origin, as pre-defined by the task. Our task was to systematize valuable information collected from different fields of science and research (competencies), to compare them with international standard databases, and thus, to discover new inter-relations, create new values. As an input, one could envisage a network of satellite data bases evaluating relevant results of scientists and research institutions. The main database itself could contain standard national and international information on environmental health care. The output of the system could be relational analysis produced by the meta-system on the basis of results provided by the satellite systems. Thus, frequently, even without carrying out a particular survey, one could already suspect that certain environmental health hazards exist, or plan and implement certain measurements and surveys in a more precisely targeted way. An unlimited number of local satellite workstation modules of experts and research institutions may be linked to the meta database. Information property created as a result of special analysis and annotation might create a knowledge basis for free access by participants. Thus not only would their scientific backgrounds be strengthened, but services would also be provided by the meta database which could be diversified continuously. The satellite systems, the sorting and retrieval functions of the database, and its graphical services would provide a loose but flexible micro-computer system that could be linked together by autonomous or networked workstations. Our system is written on FoxPro and uses FoxGraph. At a medium level of capacity, it requires 1 MB free RAM and 14-16 MB fixed memory. The system already shows a certain specialization: the 'PubHealth' system from general issues of environmental health care leans towards problems related to sub-toxic long term effects and correlations to health insurance risk assessment (cost-benefit, risk-benefit analysis). However, new issues are also emerging when experts wish foremost to utilize the philosophy of the system (e.g., epidemiological mental-hygienic surveys related to life style and social status).

Computer Communication Networks↗

PubMed1994

[Colonic complications associated with acute necrotizing pancreatitis].

Authors found colonic involvement in 9 cases of the 83 patients who have undergone surgical procedure for acute pancreatitis (10.8%). The form of the complications were inoperable extensive necrosis in two, resectable isolated necrosis in four and colo-cutaneous fistula in three cases. Acute extrapancreatic fat necrosis usually caused segmental necrosis of the colon while abscess generally led to fistulization. Complications based rather on ischaemic damage of mesocolon than direct enzymatic influence. Five patients died. Analysing this late, severe involvement, which appeared average on 18-th day, authors try to find relationships between pathomechanism, therapy and mortality rate.

Abscess↗