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Biomedical subjects

M Marczak

Publications and source records attributed to M Marczak.

At least 19 recordsLinked to original sources
PubMed2006

The influence of acute progressive hypoxia on bioelectrical activity of the brain.

Hypoxia, a noxious and hyperventilatory stimulus and a modifier of neuronal metabolism, could influence cortical function. In this study we attempted to assess any such influence, its determinants, and particularly the role in it of the accompanying hypoxic emotional distress. We addressed the issue by examining the associations among EEG, ventilation, and anxiety during progressive poikilocapnic hypoxia (end-point SaO(2) approximately 75%) in 12 awake healthy volunteers (mean age 27.5 +/-0.7 yr). All subjects hyperventilated in response to hypoxia and 3 of them had a high level of anticipatory anxiety that forced one person to discontinue the test. We failed to show any major effect of hypoxia on the EEG pattern analyzed by visual inspection or wavelet power spectra. Therefore, no relationship between the ventilatory and cortical activity responses to hypoxia could be established. Cortical activity changes appeared, however, in the subjects who experienced emotional distress during the test. These changes were apparent on an expanded analysis of the EEG signal by the use of the Lempel-Ziv complexity that takes into account the ordering of variations in the signal, rather than only the relative frequency of events analyzed by the Shannon entropy. The Lempel-Ziv complexity offers promise as a novel method for unraveling fine and otherwise unexpressed alterations in cortical bioelectrical activity.

Adult↗
PubMed2005

Neurotransmitter mechanisms in the enhancement of the hypoxic ventilatory response by antecedent hyperoxia in the anesthetized rat.

A brief period of antecedent oxygen breathing enhances the ventilatory response to hypoxia. The mechanisms of this phenomenon are uncertain and have been variably linked to the central glutamatergic or nitrergic pathways. In the present study we put a question of how blockade of either neurotransmitter pathway would compare with the concurrent blockade of them both in terms of the enhancement of posthyperoxic hypoxic ventilation. The study was performed on the anesthetized, vagotomized, spontaneously breathing rats divided into the following experimental groups: control NaCl-treated, glutamate blocker 2-amino-5-phosphonopentanoic acid (AP5)-treated, nitric oxide synthase blocker 7-nitroindazol (7NI)-treated, and AP5+7NI-treated. The protocol consisted of measuring the ventilatory response to 12% O2, a steady- state poikilocapnic hypoxia, undertaken in three consecutive conditions in each animal: the initial control, 25 min after injection of a given chemical agent, and then after a 15-min period of oxygen breathing. Respiration was evaluated from the diaphragmatic EMG signal. We found that the posthyperoxic hypoxic ventilatory enhancement was but partially dampened by either AP5 or 7NI. Concurrent administration of the two blockers further diminished, but did not abolish, the hypoxic ventilatory enhancement. We conclude that although the glutamate-NO system accounts for an appreciable part of the posthyperoxic hypoxic ventilatory enhancement, other, as yet unclear, mechanisms contribute as well. These mechanisms may be worth exploring given the substantial enhancing effect the antecedent oxygen has on hypoxic hyperventilation.

2-Amino-5-phosphonovalerate↗
PubMed2005

Stability of ascorbyl palmitate molecule in the rat brain.

Recent investigations have shown the ability of ascorbyl palmitate (AP), a bioactive, lipid-soluble ester of ascorbic acid (AA), to penetrate neural tissues. This study seeks to determine the occurrence of hydrolysis of AP molecule in brain tissue, which could rather point to the action of AA alone carried over the biological barrier and then released from the AP compound. The integrity of AP molecule was examined qualitatively in the rat brain by thin-layer-chromatography. AP was injected into an internal carotid artery in a dose of 75 mg per rat after tying off the common and external carotid arteries at the same side. The rats were sacrificed 15 min later, the brain tissue was extracted with chloroform/methanol and chromatographed. The AP bands plated from the samples ipsilateral to the injection side strictly corresponded to the AP standard's location and were clearly separated from the AA standard with no overlap. The experiment showed that AP resists hydrolysis in the brain and thus the short-term biological effects of AP may be ascribed to the action of an intact ester molecule. The results may help elucidate the biological action of AP, a compound that increasingly attracts attention for biomedical use due to its antioxidant potential and ability to penetrate into the membrane signaling target sites.

Animals↗
PubMed2004

Increased local vascular endothelial growth factor expression associated with antitumor activity of proteasome inhibitor.

Inhibition of the proteasome, a multicatalytic proteinase complex, is an attractive approach to cancer therapy. Here we report that a selective inhibitor of the chymotrypsin-like activity of the proteasome, PSI (N-benzyloxycarbonyl-Ile-Glu(O-t-butyl)-Ala-leucinal) may inhibit growth of solid tumors not only through apoptosis induction, but also indirectly--through inhibition of angiogenesis. Two murine tumors: colon adenocarcinoma (C-26) and Lewis lung carcinoma (3LL) were chosen to study the antitumor effect of PSI. In an in vivo model of local tumor growth, PSI exerted significant antitumor effects against C-26 colon carcinoma, but not against 3LL lung carcinoma. Retardation of tumor growth was observed in mice treated with both 10 nmoles and 100 nmoles doses of PSI and in the latter group prolongation of the survival time of tumor-bearing mice was observed. PSI inhibited angiogenesis in the C-26 growing tumors with no such effect in 3LL tumors. Unexpectedly, that activity was associated with upregulation of vascular endothelial growth factor (VEGF) at the level of mRNA expression and protein production in C-26 tumors treated with PSI. C-26 cells treated with PSI produced increased amounts of VEGF in vitro in a dose- and time-dependent manner. We demonstrated that in C-26 colon adenocarcionoma higher VEGF production may render endothelial cells susceptible to the proapoptotic activity of PSI and is associated with inhibition of tumor growth.

Adenocarcinoma↗
PubMed2004

Oxygen breathing and ventilation.

We investigated the ventilatory response to normobaric poikilocapnic hyperoxia in healthy subjects. The study was carried out in 26 subjects of the mean age 26 +/- 0.9 (SE) years, who breathed pure oxygen through a two-way valve for 10 min. The subjects were in the sitting position with a mouthpiece and nose clip attached. Ventilatory flow was recorded using a pneumotachograph and minute ventilation was calculated from the tidal and frequency components. The SaO(2) and alveolar CO(2) tension were continuously monitored. Ten of the same subjects constituted a control group in which room air was substituted for oxygen and the tests repeated in the same way at another occasion. We found that oxygen breathing caused a transient 8.4% decline in ventilation, whose nadir was 1 min after the introduction of oxygen. Thereafter, ventilation increased significantly above the baseline value and showed a further rising tendency toward the end of the test. We conclude that acute oxygen treatment is unlikely to have a major inhibitory effect on the carotid body-dependent ventilatory drive in normal subjects. The determinants of the hyperoxic ventilatory stimulation remain to be established in further studies.

Administration, Inhalation↗
PubMed2004

Hypoxic ventilatory profile in the anesthetized rat.

In the present study we investigated whether hypocapnia that accompanies hypoxic hyperventilation might affect the biphasic, stimulatory/depressant, ventilatory response to hypoxia. The experiments were carried out in anesthetized, vagotomized, spontaneously breathing, and poikilocapnic rats. The animals were subjected to acute steady-state hypoxia consisting of 12% O(2) in N(2) in inspiratory mixture. Ventilation and its frequency and volume components were assessed from the integrated electromyographic activity of the diaphragm. We found that despite the development of significant hypocapnia, the hypoxic ventilatory response consisted of rapid stimulation followed by a gradual decline. The frequency component contributed more to the ventilatory increase than that of volume. The results indicate that the hypoxic ventilatory profile in the anesthetized poikilocapnic rat resembles that known to be present during isocapnia. We conclude that hypocapnia neither hampers the hypoxic ventilatory reactivity nor alters the biphasic hypoxic ventilatory profile. These observations may aid planning experimental rat model studies.

Anesthesia↗
PubMed2004

The aging carotid body.

The respiratory system is subject to the aging process, which could limit its responsiveness to hyperventilatory stimuli. Attenuation of the ventilatory response to hypoxia in old age is, as yet, an unresolved issue. Such attenuation may be germane for the pathogenesis of respiratory disorders developing more often in elderly subjects. The aim of this study was to determine the potential adverse effects of age on the morphology and function of carotid bodies. Morphology was studied at the level of electron microscopy on carotid bodies dissected from adult young (3 months) and old (>2 years) rats and function by comparing the hypoxic ventilatory response in populations of young (mean age 24 years) and old (mean age 71 years) female subjects. The human protocol consisted of a progressive hypoxia test, based on a rebreathing technique in a closed system. The hypoxic ventilatory response was evaluated from the slopes of minute ventilation on arterial oxygen saturation. The results of the morphological study showed degenerative changes developing with age in the ultrastructure of carotid bodies. On the other side, respiratory responses to hypoxia in old women were well preserved and were no less than those in young women. Therefore, a discrepancy appeared between the morphological and functional aspects. These findings suggest development of compensatory mechanisms in brain respiratory areas which maintain primary defensive reflexes, such as the hyperventilation of hypoxia.

Adult↗
PubMed2003

Cortical activity during hypoxic hyperventilation.

This study seeks to determine the pattern of electroencephalogram changes during stimulatory ventilatory responses to acute progressive hypoxia. Electroencephalograms were recorded in the 10-20 electrode system during progressive poikilocapnic hypoxic tests based on the rebreathing routine. Healthy subjects were used for he study. A major finding was that hypoxia decreased the power spectra of the alpha activity. The decrease was surprisingly rapid and greater at mild hypoxic desaturation when pulmonary ventilation was about to pick up than during the maximum hypoxic hyperventilation. The possible relation of hypoxic decline in brain bioactivity to the manifestation of hypoxic hyperventilation remains to be elucidated in further studies.

Adult↗
PubMed2001

Antitumor activity of tributyrin in murine melanoma model.

Butyric acid has been known to inhibit growth and to induce differentiation of a variety of tumor cells. Butyrate-treated tumor cells have also been observed to undergo apoptosis. Although butyrate compounds have demonstrated antitumor activity in murine tumor models and have already been admitted to clinical trials in tumor patients, the exact mechanism of their antitumor effects has not been elucidated. The results of our study showed antitumor activity of tributyrin, a butyric acid prodrug, in murine melanoma model and are strongly suggestive that antiangiogenic effects could participate in antitumor effects of butyrate compounds in vivo.

Animals↗
PubMed2000

Interleukin 12 and indomethacin exert a synergistic, angiogenesis-dependent antitumor activity in mice.

Nonsteroidal anti-inflammatory drugs have been shown to reduce the incidence and mortality from colorectal cancer. It has recently been demonstrated that these drugs are capable of suppressing the production of pro-angiogenic factors from tumor cells. The mechanisms of antitumor action of interleukin 12 include the enforced secretion of anti-angiogenic factors and stimulation of antitumor immunity. Therefore, we hypothesized that the combination of a model nonsteroidal anti-inflammatory drug--indomethacin and interleukin 12--would result in enhanced angiogenesis-dependent antitumor effects against a colon-26 carcinoma cells transplanted into syngeneic mice. As expected the combined administration of both agents simultaneously resulted in a strengthened antitumor activity that was manifested as a retardation of tumor growth and prolongation of mouse survival. Importantly some mice were completely cured after the combined treatment. As administration of interleukin 12 and indomethacin resulted in enhanced inhibition of angiogenesis it seems possible that prevention of new blood vessel formation is one of the mechanisms responsible for the observed antitumor effects.

Animals↗
PubMed1999

Lovastatin and tumor necrosis factor-alpha exhibit potentiated antitumor effects against Ha-ras-transformed murine tumor via inhibition of tumor-induced angiogenesis.

Lovastatin, a drug commonly used in the treatment of hypercholesterolemia, has previously been reported to exert potentiated antitumor activity when combined with either tumor necrosis factor-alpha (TNF-alpha), cisplatin or doxorubicin in a melanoma model in mice. Since lovastatin interferes with the function of ras oncogene-encoded (Ras) proteins, we have investigated the antitumor activity of lovastatin and TNF-alpha using a Ha-ras-transformed murine tumor model. In in vitro studies, lovastatin inhibited the growth of cells transformed with Ha-ras oncogene (Ras-3T3 and HBL100-ras cells) more effectively than control NIH-3T3 and HBL100-neo cells. In in vivo experiments, the Ras-3T3 tumor demonstrated significantly increased sensitivity to combined treatment with both lovastatin (50 mg/kg) and TNF-alpha (1 microg/day) compared with either agent alone. Combined treatment with both agents also resulted in greater inhibition of blood-vessel formation. Ras-3T3 tumor cells produced increased amounts of vascular endothelial growth factor (VEGF) and lovastatin effectively suppressed VEGF production by these cells. Our results suggest that lovastatin increases antitumor activity of TNF-alpha against tumor cells transformed with v-Ha-ras oncogene via inhibition of tumor-induced blood-vessel formation.

3T3 Cells↗
PubMed1999

Apolipoprotein E polymorphism in indigenous Australians: allelic frequencies and relationship with dyslipidaemia.

OBJECTIVES: To determine the apolipoprotein E (apoE) allelic frequencies and the effect of apoE genotype on lipid concentrations in indigenous Australian subjects. DESIGN: Cross-sectional study. SUBJECTS AND SETTING: 155 indigenous Australians (92 women and 63 men) of mean (+/- standard deviation) age 45 +/- 17 years (SD +/- 50) were recruited without regard to history of atherosclerotic disease, in collaboration with community-based health centres in five indigenous communities in south-east Queensland. For comparison, 113 subjects of European descent and similar age distribution from the Brisbane and Gold Coast regions were also studied. MAIN OUTCOME MEASURES: ApoE allelic frequency; apoE genotype; sex; age; diabetes status; body mass index; history of atherosclerotic vascular disease; and concentrations of total cholesterol, triglyceride, HDL-cholesterol and LDL-cholesterol. RESULTS: The frequency of the apoE4 allele was found to be significantly higher in the indigenous subjects than in the subjects of European descent (P < 0.001). Among indigenous subjects, those with the apoE4 allele tended to have higher triglyceride concentrations and had significantly lower HDL-cholesterol concentrations than those with the apoE3/3 and 3/2 genotypes. CONCLUSIONS: ApoE allelic frequency is likely to be one of the cluster of factors contributing to the high cardiovascular mortality of indigenous Australians.

Adult↗
PubMed1999

Plasma homocysteine levels in indigenous Australians.

OBJECTIVES: To determine plasma homocysteine levels in indigenous Australians living in urban areas, and the relationship of these levels with other risk factors in this population. DESIGN: Cross-sectional study. SUBJECTS AND SETTING: 365 urban indigenous Australian subjects, 153 men and 212 women, mean (SE) age 42 (1) years, ascertained without regard to history of atherosclerotic disease, in collaboration with community-based health centres in five indigenous communities in south-east Queensland, 1997-1998. MAIN OUTCOME MEASURES: Plasma homocysteine levels, age, sex, smoking history, metformin therapy, history of atherosclerotic vascular disease, serum creatinine level, red cell folate and serum vitamin B12 levels. RESULTS: 89 subjects (24%) had plasma homocysteine levels 15 mumol/L or above. Homocysteine levels were higher in men than in women (men: 14.4 mumol/L; 95% confidence interval [CI], 13.6-15.2; women: 11.9 mumol/L; 95% CI, 11.4-12.5) (P < 0.001); correlated with age (P < 0.001); higher in current smokers (P = 0.02); higher in subjects taking metformin therapy (P = 0.007); and higher in subjects with a history of atherosclerotic vascular disease (P < 0.001). Homocysteine levels were also correlated with serum levels of creatinine (P < 0.001), red cell folate (P < 0.001), and vitamin B12 (P < 0.001). CONCLUSIONS: These data indicate that the high plasma levels of homocysteine of Australian indigenous subjects are associated with a history of vascular disease, and correlated with, among other things, smoking, and folate and vitamin B12 nutritional deficiency. These are potentially reversible risk factors, and our data suggest that focusing public health initiatives on these issues may reduce the high prevalence of cardiovascular disease in the Australian indigenous population.

Adult↗
PubMed1999

[Local parabulbar anesthesia with Greenbaum cannula for most common ophthalmic operations].

PURPOSE: To compare two methods of local anesthesia in ophthalmic surgery: classic retrobulbar and new--parabulbar made with Greenbaum cannula and to try to assess new method. MATERIAL AND METHODS: 300 patients underwent most common ophthalmic operations: ECCE + PCLI and glaucoma surgery. 150 of them were anesthetised by retrobulbar and 150 by parabulbar (flush) with Greenbaum cannula methods. We compared the presumed influence of these two types of anesthesia on the operations assessing the following: the occurrence "vis a tergo" and posterior capsule rupture. We compared also efficacy of both methods (analgesia and akinesia) and complications (retrobulbar hematoma, globe perforation). We minimalized the volume of anesthetic mixture used in retrobulbar method to 1.5 ml (0.5 ml 0.5% bupivacaine + 1 ml 2% xylocaine). RESULTS: The number of complications was lower in the group anesthetised by parabulbar method. The complications of local anesthesia were bigger in retrobulbar method (retrobulbar hematoma, globe perforation). Anesthesia in parabulbar method in spite of little volume of anesthetic mixture was very good but akinesia--slightly weaker comparing to retrobulbar injection. CONCLUSIONS: Parabulbar anesthesia made with Greenbaum cannula is a very good, safe method giving very good anesthesia no possibility of globe perforation or retrobulbar hematoma, but the method is for skilled surgeons because of weaker akinesia.

Anesthesia, Local↗
PubMed1997

Antitumor effects of the combination immunotherapy with interleukin-12 and tumor necrosis factor alpha in mice.

There is strong evidence that antitumor activity of interleukin-12 (IL-12) in vivo is mediated, in part, through interferon (IFN gamma) produced by IL-12-stimulated natural killer and T cells. Since IFN gamma and tumor necrosis factor alpha (TNF alpha) have been reported to synergize in antitumor effects in a number of models, we decided to examine whether the combined treatment with recombinant mouse IL-12 and recombinant human TNF alpha would produce similar effects. The efficacy of the combined IL-12/TNF alpha immunotherapy was evaluated in three tumor models in mice: B16F10 melanoma, Lewis lung (LL/2) carcinoma and L1 sarcoma. Intratumoral daily injections of 1 microgram IL-12 in combination with 5 micrograms TNF alpha into B16F10-melanoma-bearing mice resulted in a significant retardation of the tumor growth as compared with that in controls and in mice treated with either cytokine alone. Similar effects were obtained using 0.1 microgram IL-12 and 5 micrograms TNF alpha in LL/2 carcinoma and L1 sarcoma models. Antitumor activity against L1 sarcoma was still preserved when TNF alpha at a low dose (1 microgram) was combined with 0.1 microgram IL-12 and applied for a prolonged time. Potentiation of antitumor effects, which was observed in IL-12/TNF alpha-based immunotherapy, could result from at least three different mechanisms, partly related to stimulation of IFN gamma and TNF alpha production in treated mice: (a) direct cytostatic/cytotoxic effects on tumor cells, (b) induction of antitumor activity of macrophages, and (c) inhibition of blood vessel formation in the tumor. Our studies demonstrate that combination tumor immunotherapy with IL-12 and TNF alpha may be more effective than single-cytokine treatment, and suggest possible mechanisms by which IL-12 and TNF alpha may exert potentiated therapeutic effects against locally growing tumors.

Animals↗
PubMed1996

Interleukin-12 inhibits angiogenesis induced by human tumor cell lines in vivo.

Tumor cell-induced angiogenesis, i.e., new blood vessel formation within tumor tissue, is an essential requirement for the growth of solid neoplasms. Interleukin-12 (IL-12) inhibits growth of a variety of experimental tumors in vivo. We tested whether antitumor activity of IL-12 is related to the inhibition of angiogenesis induced by tumor cell lines. Angiogenesis was induced in x-ray immunosuppressed Balb/c mice by intradermal injection of the following human tumor cells: T47D, originating from mammary carcinoma; A431, derived from vulval carcinoma; and Skv, established from bowenoid papulosis, Systemic treatment of the mice with murine IL-12 significantly decreased angiogenesis induced by human tumor cells in a time-and dose-dependent manner. Preincubation of human cells in vitro with IL-12 did not inhibit tumor cell-induced angiogenesis, suggesting that the antiangiogenic capacity of IL-12 is restricted to in vivo conditions. Treatment of the mice with rat antibody against murine interferon-gamma (IFN-gamma) resulted in counteracting the antiangiogenic effect of murine IL-12. Furthermore, human IFN-gamma inhibited the angiogenic activity of human tumor cell lines. This indicates that IFN-gamma is a mediator of the antiangiogenic effect of IL-12. The results show that the mechanism of antitumor action of IL-12 may depend not only on the immunostimulatory activity of this cytokine but also on its effect on tumor cell-induced angiogenesis. IL-12 should be considered as a potential candidate for the treatment of angiogenesis-dependent malignancies.

Animals↗