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Biomedical subjects

H Salman

Publications and source records attributed to H Salman.

At least 19 recordsLinked to original sources

Poly(D,L-lactide-coglycolide) particles containing gentamicin: pharmacokinetics and pharmacodynamics in Brucella melitensis-infected mice.

Drug delivery systems containing gentamicin were studied as a treatment against experimental brucellosis in mice. Micro- and nanoparticles prepared by using poly(D,L-lactide-coglycolide) (PLGA) 502H and microparticles made of PLGA 75:25H were successfully delivered to the liver and the spleen, the target organs for Brucella melitensis. Both polymers have the same molecular weight but have different lactic acid/glycolic acid ratios. Microparticles of PLGA 502H and 75:25H released their contents in a sustained manner, in contrast to PLGA 502H nanoparticles, which were degraded almost completely during the first week postadministration. The values of the pharmacokinetic parameters after administration of a single intravenous dose of 1.5 mg/kg of body weight of loaded gentamicin revealed higher areas under the curve (AUCs) for the liver and the spleen and increased mean retention times (MRTs) compared to those for the free drug, indicating the successful uptake by phagocytic cells in both organs and the controlled release of the antibiotic. Both gentamicin-loaded PLGA 502H and 75:25H microparticles presented similar pharmacokinetic parameter values for the liver, but those made of PLGA 75:25 H were more effective in targeting the antibiotic to the spleen (higher AUCs and MRTs). The administration of three doses of 1.5 mg/kg significantly reduced the load associated with the splenic B. melitensis infection. Thus, the formulation made with the 75:25H polymer was more effective than that made with 502H microspheres (1.45-log and 0.45-log reductions, respectively, at 3 weeks posttreatment). Therefore, both, pharmacokinetic and pharmacodynamic parameters showed the suitability of 75:25H microspheres to reduce the infection of experimentally infected mice with B. melitensis.

Animals↗

Solitary modes of bacterial culture in a temperature gradient.

We study the behavior of a bacterial culture in a one-dimensional temperature gradient. The bacteria first accumulate near their natural temperature due to thermotaxis. The maximum of the bacterial density profile then drifts to lower temperature with a velocity proportional to the initial concentration of bacteria (typical velocity 0.5 microm/sec). Above a critical concentration of 10(8) cells/cm(3), a new mode develops from the initial accumulation in the form of a sharp pulse moving at a faster velocity ( approximately 3.5 microm/sec). The time of development of this mode diverges as the concentration approaches its critical value. This mode is a result of a positive feedback mechanism provided by interbacterial communication. A theoretical model shows good agreement with the experimental results.

Amino Acids↗

Relationship between temperature and apoptosis of human peripheral blood mononuclear cells.

To examine the effect of various incubation temperatures on the apoptotic death of human peripheral blood mononuclear cells (PBMC), we incubated cells at 37 degrees C, 22 degrees C, and 4 degrees C for 1 and 24 hours. In addition, cells incubated at 4 degrees C for 3, 6, and 9 hours were rewarmed to 37 degrees C until a total incubation time of 24 hours was reached. The percentage of apoptotic cells was detected by a flow cytometric assay using propidium iodide staining. Incubation of PBMC at the above-mentioned temperatures for 1 hour did not affect the percentage of apoptotic cells. However, incubation at 4 degrees C for 24 hours resulted in the lowest percentage of apoptotic cells compared to those incubated at 22 degrees C and 37 degrees C. Rewarming of the cells to 37 degrees C increased the percentage of apoptotic cells to a level similar to that of the controls (incubated at 37 degrees C). Because PBMC are closely involved in the normal function of the immune system, the results of the study should be considered in cases in which these cells are exposed to various thermal conditions.

Apoptosis↗

Pure red cell aplasia--a rare disease with multiple causes.

Pure red cell aplasia (PRCA) is a relatively rare disease although multiple factors are implied in the pathogenesis of its development. A slow progressive normocytic-normochromic anemia and reticulocytopenia, without leukopenia and thrombocytopenia in a patient who, except pallor, does not show abnormal findings on physical examination, should arise the suspicion that he has PRCA. Search for underlying diseases or infections and intake of drugs may help for the establishment of the diagnosis of acquired PRCA. Lack of erythroblasts in the bone marrow with normal development of the other hemopoietic series, as well as high level of serum erythropoietin are important clues for the diagnosis. Elimination of potentially causative factors, administration of immunosuppressive agents and/or recombinant erythropoietin, preferably epoetin beta, may induce remission and complete recovery.

Adrenal Cortex Hormones↗

On the mechanism of post-splenectomy leukocytosis in mice.

BACKGROUND: Increased number of peripheral white blood cells (PWBCs) has been noted after removal of the spleen. DESIGN: To clarify the possible mechanisms by which splenectomy affects the PWBC number, the percentage of apoptotic PWBCs, the number and migration rate of peritoneal cells, as well as the 3H-TdR incorporation into PWBCs, were examined in splenectomized, sham-operated and control mice. In addition, the effect of control plasma injected to splenectomized animals on the number of PWBCs was examined. RESULTS: One and two months after splenectomy the PWBC counts significantly increased, whereas the percentage of apoptotic PWBCs and the number of cells in the peritoneal cavity decreased in comparison with that of the control and sham-operated mice. Seventeen days after injection of carboxy-fluorescein diacetate succinimidyl ester (CFSE)-labelled peritoneal cells into the peritoneal cavity of the animals, their number was significantly higher in the peripheral blood and lower in the peritoneal cavity of the splenectomized animals in comparison with that of the control and sham-operated mice. Injection of control plasma into the splenectomized mice prevented the development of postsplenectomy leukocytosis. Finally, 3H-TdR incorporation into nonstimulated and Con A stimulated PBMCs from the splenectomized mice was higher as compared with cells from the control and sham-operated mice. CONCLUSIONS: The results of the study present several mechanisms that may clarify the cause of postsplenectomy leukocytosis.

Animals↗

Interaction between phagocytosis and IL-1beta production by rat peritoneal macrophages.

The capacity of rat peritoneal macrophages to produce interleukin-1beta (IL-1beta) following phagocytosis of latex particles in vivo and in vitro was examined. In both cases, a marked increase in IL-1beta secretion was observed, although the level of the cytokine secreted in vivo was higher than that observed after incubation of the cells with latex beads in vitro. It is presumed that this difference is due to stimulation of the peritoneal macrophages by endogenous produced factors/cytokines prior and during phagocytosis in vivo. Macrophages stimulated with LPS showed a level of IL-1beta almost identical to that obtained after incubation with latex. Following phagocytosis in vivo and further stimulation with LPS in vitro, the cells showed an additional increase in IL-1beta production, whereas this additive effect could not be observed when incubation with both latex and LPS was carried out in vitro. The results suggest different patterns for IL-1beta production by rat peritoneal macrophages, depending on the way they are stimulated for phagocytosis.

Animals↗

Serial passage of Chlamydia spp. in sub-inhibitory fluoroquinolone concentrations.

We investigated the in vitro development of fluoroquinolone resistance in Chlamydia trachomatis and Chlamydia (Chlamydophila) pneumoniae grown in McCoy cell monolayers in supplemented Eagle's minimum essential medium. With C. trachomatis, initial passages at sub-inhibitory fluoroquinolone concentrations did not affect fluoroquinolone susceptibility. However, after an initial lag of 10-24 passages (depending upon the fluoroquinolone used), fluoroquinolone resistance developed rapidly. The final fluoroquinolone MIC after a total of 30 passages was >256 times the MIC of the original wild-type strain with ofloxacin or ciprofloxacin passage. Analysis of the quinolone-resistance determining regions of two quinolone-resistant C. trachomatis mutants obtained after 30 passages showed that both isolates had a single serine to isoleucine substitution at amino acid position 83 in GyrA. In stark contrast, with C. pneumoniae no reduced fluoroquinolone susceptibility could be sustained, even after 30 passages with moxifloxacin or ofloxacin. With sparfloxacin passage, some indication of resistance was observed but no viable organisms could be isolated for further investigation. It is possible that fluoroquinolone-resistant C. pneumoniae are less able to survive than wild type, which may explain why resistance does not develop readily.

Anti-Infective Agents↗

Kinetics and mechanism of DNA uptake into the cell nucleus.

Gene transfer to eukaryotic cells requires the uptake of exogenous DNA into the cell nucleus. Except during mitosis, molecular access to the nuclear interior is limited to passage through the nuclear pores. Here we demonstrate the nuclear uptake of extended linear DNA molecules by a combination of fluorescence microscopy and single-molecule manipulation techniques, using the latter to follow uptake kinetics of individual molecules in real time. The assays were carried out on nuclei reconstituted in vitro from extracts of Xenopus eggs, which provide both a complete complement of biochemical factors involved in nuclear protein import, and unobstructed access to the nuclear pores. We find that uptake of DNA is independent of ATP or GTP hydrolysis, but is blocked by wheat germ agglutinin. The kinetics are much slower than would be expected from hydrodynamic considerations. A fit of the data to a simple model suggests femto-Newton forces and a large friction relevant to the uptake process.

Adenosine Triphosphate↗

Patients' satisfaction with the staff function in an emergency department.

Patients' satisfaction with the functional capacity and attitude of the permanent staff working in the morning hours in the emergency department (ED) of a community hospital was compared with that of the staff working during the evening and night shifts. A total of 285 patients given care in the ED were interviewed according to a 'satisfaction' questionnaire regarding the function and attitude of the ED staff during the morning and evening/night shifts. The mean waiting time until a doctor was seen during the morning shift was 25 +/- 17 minutes for non-hospitalized patients and 25 +/- 8 minutes for the hospitalized ones, whereas during the evening and night hours the waiting times were 22 +/- 17 minutes and 19 +/- 13 minutes respectively. The number of laboratory examinations performed during the evening and night shifts markedly exceeded that carried out during the morning. The mean staying time in the ED for both non-hospitalized and hospitalized patients during the morning was by 23% shorter than that during the evening and night shifts. The patients expressed their overall satisfaction with the ED staff in both shifts with high evaluation marks. It is concluded that the survey indicates that the permanent ED staff during the morning hours are more efficient compared with those working during the evening and night shifts.

Adolescent↗

Effect of colon carcinoma cell supernatants on cytokine production and phagocytic capacity.

The ability of colon carcinoma cells to produce IL-1 beta, IL-6 and TNF alpha, and the effect of tumor cell supernatants (sups) on the capacity of peripheral blood mononuclear cells to produce these three cytokines was examined. In addition, the effect of colon carcinoma cell sups on the engulfing capacity of phagocytic cells was detected. The results showed that IL-1 beta, IL-6 and TNF alpha levels were significantly higher in tumor cell sups compared with those of autologous colon mucosal cells obtained from healthy tissue. Tumor cell sups caused a decrease in both phagocytic capacity, and the number of latex particles engulfed by each individual cell.

Culture Media, Conditioned↗

Abolition of exercise induced positive U-wave after coronary angioplasty: clinical implication.

OBJECTIVE: We prospectively studied the course of exercise induced positive U-wave before and after percutaneous transluminal coronary angioplasty (angioplasty). BACKGROUND: Negative U-wave in ECG is known to be associated with the myocardial ischemia in the territory of the left anterior descending artery. Positive U-wave needs further evaluation to prove its diagnostic value in localization of coronary artery disease. METHOD: Twenty patients demonstrated exercise induced positive U-wave from a cohort of 730 patients referred because of chest pain. Exercise was carried to > or =90% of target heart rate. They underwent angiography and subsequent angioplasty for stenosis of 70% or greater. The exercise test was repeated post angioplasty. Careful screening for clinical endpoints and presence of ST segment depression and positive U-wave was done during exercise and the first 3 min of the recovery phase. RESULTS: Fifteen patients had isolated exercise induced U-wave and five had additional ST segment depression of > or =1 mm. Significant stenosis (>70% diameter reduction) of the circumflex artery was seen in 11 (55%) and of the right coronary artery in 9 (45%) patients. Coronary artery stenosis was reduced from 90+/-2% to 13+/-1% (mean+/-S.D.) P<0.001. On repeat of the exercise test U-wave and ST depression disappeared in all 20 individuals. Effort tolerance was improved after angioplasty for a mean duration of 3 min and 38 s, P<0.001. CONCLUSION: Exercise induced positive U-wave is an infrequent but specific marker of significant single coronary (circumflex or right) artery stenosis. It may lend itself to the detection of restenosis.

Adult↗

Ultrastructure and phagocytic activity of rat peritoneal macrophages exposed to low temperatures in vitro.

Hypothermia affects various components of the immune system, leading to impaired immune resistance. To examine the in vitro effect of low temperature on the ultrastructure and phagocytic function of rat peritoneal macrophages, cells were incubated at 4, 10, 24, and 37 degrees C for 60 min. Subsequently, their ultrastructure and capacity to engulf latex particles and generate superoxide anions were evaluated. The results showed a close inverse relationship between incubation temperature and ultrastructural changes, i.e., the lower the temperature, the higher the number of altered cells. In addition, at lower temperatures the number of cells capable of phagocytosis was reduced; the cells engulfed fewer particles per cell and generated less superoxide anions. These findings may be relevant for explaining the increased susceptibility to bacterial infections under hypothermic conditions.

Animals↗

Interleukin-3 and stress.

The importance of cytokines as mediators in numerous physiologic and pathologic processes became apparent in the early seventies. In a relatively short period of time the number of characterized and functionally defined interleukins increased rapidly. Concomitantly, the understanding of their role in various important reactions in different systems of the organism in general, and in the interaction between the immune, central nervous and neuroendocrine systems in particular increased. IL-3 is one of the cytokines of great significance for hematopoiesis. In addition, it was shown that interleukin-3 (IL-3) participates in the response of the organism to various types of stress. Surprisingly enough, the reports on its production and activation during or following stress are rather scarce. Therefore, the purpose of this review is to try and compile the information on IL-3 and its role in different types of stress, and also to contribute our own modest experience on the subject.

Animals↗

Effect of diazepam on the immune response of rats exposed to acute and chronic swim stress.

To examine the effect of the anti-stress agent diazepam on the immune response, rats were exposed either to acute swim stress, i.e., swimming once only for 30 minutes (non-trained swimmers), or to chronic stress with gradual progressive training for 6 weeks (trained swimmers). Both groups of animals were divided into subgroups treated before swimming with and without diazepam, 1 mg/kg, administered i.m. The phagocytic capacity and superoxide anion generation of the peritoneal macrophages was examined. In addition, the proliferative response of the splenic cells (splenocytes) to concanavalin A (Con A) and phytohemagglutinin (PHA), as well as the serum corticosterone levels were investigated. Diazepam abolished increased superoxide anion production in both non-trained and trained swimmers. In non-trained swimmers, the number of latex particles internalized by each cell was decreased and further reduced by the drug. In trained rats treated with diazepam, the percentage of phagocytosing cells remained reduced compared to controls, whereas the drug prevented a decrease in the engulfing capacity of individual cells. Diazepam lowered the suppressed proliferative response of the splenocytes to PHA found in non-trained swimmers. It is concluded that diazepam modifies the immune response of rats exposed to acute and chronic swim stress.

Animals↗

Hypothermia affects the phagocytic activity of rat peritoneal macrophages.

To examine the effect of hypothermia on the phagocytic capacity of rat peritoneal macrophages for latex particles, male Wistar rats were exposed to 4 degrees C for 8 and 72 h. While the shorter exposure to cold did not affect body temperature and macrophage function, animals exposed to 4 degrees C for 72 h showed a mean decrease of their body temperature by 1.5 degrees C. The superoxide anion production was significantly increased whereas the number of phagocytic cells decreased. In addition, the mean number of latex particles engulfed by each individual cell was lower than that of controls. Peripheral blood mononuclear cells (PBMC) of these animals showed lower mitogen response to phytohaemagglutinin (PHA), while that for concanavalin A (Con-A) remained unchanged. Peritoneal macrophages exposed in vitro to 24 degrees C for 60 min showed a decreased phagocytic capacity in comparison with macrophages kept at 37 degrees C, an observation suggesting the development of an indigenous cell defect for phagocytosis at lower temperatures. On the other hand, the effect of additional humoral factor(s) on macrophage activity, such as an increase in serum level of catecholamines and corticosterone, cannot be excluded. The results of the study may contribute to understanding the predisposition to infections during exposure to cold.

Animals↗

Lymphocytic intracellular calcium in a patient with complicated verapamil overdose.

Overdose with calcium channel blockers (CCBs) may lead to serious complications. CCBs act by blocking calcium entry into the cell, thus lowering intracellular calcium ([Ca2+]i). [Ca2+]i during CCB overdose has not yet been reported. We measured [Ca2+]i in lymphocytes of a patient with acute verapamil overdose with a complex clinical picture. A 59-year-old woman was admitted after a suicidal ingestion of 7200 mg of a sustained-release verapamil preparation. She presented with hypotension, complete atrioventricular block, stupor, hypokalemia, and hyperglycemia. Acute oliguric renal failure, acute pancreatitis, and the adult respiratory distress syndrome further complicated her medical course. Treatment was supportive and she recovered completely. Intracellular calcium ([Ca2+]i) was measured in the patient's lymphocytes using a spectrofluorometer with the calcium-sensitive dye Fura-2-acetoxymethyl ester. Thirty nine hours after the ingestion, [Ca2+]i was low at 52 nM (compared with 80 nM in a healthy control subject). Lymphocytic [Ca2+]i did not respond to stimulation with phytohemagglutinin (PHA). Fourteen days after the verapamil overdose, after the patient had recovered completely, lymphocytic [Ca2+]i was still low at 55 nM. At this time, there was an incomplete response to PHA in the lymphocytes. Three months after the ingestion, [Ca2+]i was normal, with a normal response to PHA. Verapamil overdose may run a complex clinical course, but full recovery is to be hoped for with full supportive care. Cellular intoxication, as reflected by low lymphocytic [Ca2+]i, is prolonged and lags behind the clinical recovery by weeks.

Calcium↗

Decreased phagocytic capacity of rat peritoneal macrophages following photon abdominal irradiation.

Photon irradiation of the abdomen may be accompanied by complications due to a decrease in the immune defense of the recipient. Since peritoneal macrophages are an important component of the immune system, we examined the phagocytic activity and oxygen superoxide anion generation by peritoneal macrophages from rats 2 and 4 weeks after abdominal irradiation with 6 MV photons applying a single dose of 2 Gy. Two and 4 weeks after irradiation, peritoneal macrophages were harvested and their capacity to engulf latex particles and to produce oxygen superoxide anions was determined. Non-irradiated rats, treated identically otherwise, served as controls. Two weeks after irradiation the phagocytic capacity and oxygen superoxide anion generation decreased by 61 and 70%, respectively, compared with controls. This tendency persisted after 4 weeks post irradiation, the decrease in both functions being 50 and 74%, respectively. It is suggested that the altered function of peritoneal macrophages following irradiation may further compromise the immune defense in patients receiving abdominal radiotherapy.

Abdomen↗

The effect of interferon on mouse myocardial capillaries: an ultrastructural study.

BACKGROUND: Cardiotoxicity, including ischemia and myocardial infarction, is one of the complications observed after treatment with interferon (IFN). Therefore, the question has been raised whether IFN may cause damage to the small myocardial blood vessels. METHODS: In this study, 400 U of IFN-alpha-2b per g of body weight were injected intraperitoneally into 2 groups of C57 B1 mice, 5 days a week for 3 and 5 months, respectively. Thin sections of the myocardium were examined with a transmission electron microscope and the ultrastructure of the capillaries was compared with that of control animals. RESULTS: The results showed a statistically significant increase in the thickness of the endothelial processes of the myocardial capillary walls in the mice treated with IFN, with a subsequent decrease in the size of the capillary lumen. The entire capillary area was not affected. CONCLUSIONS: These findings may serve as an additional explanation for the cardiac complications observed in patients treated with IFN.

Animals↗