Zinc supplementation restores plasma concentrations of zinc and thymulin in patients with Crohn's disease

The aim of this work was to evaluate whether oral supplementation with zinc sulphate (ZnSO₄) could restore thymic endocrine function in patients with Crohn's disease who showed decreased plasma concentrations of zinc and active thymulin, a zinc-dependent thymic hormone. Twenty-seven patients in clinical remission were randomly assigned to receive, for 3 months, one of the following treatments: 60 mg/day ZnSO4; 200 mg/day ZnSO4 or placebo. Plasma thymulin activity and zinc concentrations significantly increased only in patients treated with 200 mg/day ZnSO₄. Lymphocyte subpopulations, within the range of normality before zinc supplementation, were unaffected by any of the administered treatments. In conclusion, low plasma concentrations of zinc and thymulin in Crohn's disease patients were restored by the administration of high doses of zinc.     

Altered levels of biochemical indices of bone turnover and bone-related vitamins in patients with Crohn's disease and ulcerative colitis

Background The pathogenesis of inflammatory bowel disease‐associated osteopenia may be related to pathological rates of bone turnover; however, the literature shows mixed results. Aim To compare bone biomarkers in inflammatory bowel disease patients (Crohn's disease: n = 68, and ulcerative colitis: n = 32, separately) with age‐ and sex‐matched healthy controls. Subjects Patients and controls were recruited from Cork University Hospital and Cork City area, respectively. Results Relative to that in their respective controls, Crohn's disease (n = 47) and ulcerative colitis (n = 26) patients (i.e. excluding supplement users) had significantly (P < 0.05–0.001) higher serum undercarboxylated osteocalcin (by 27% and 63%, respectively) and bone‐specific alkaline phosphatase (by 15% and 21%, respectively) and urinary Type I collagen cross‐linked N‐telopeptides concentrations (by 87% and 112%, respectively). Relative to that in their respective controls, Crohn's disease and ulcerative colitis patients had significantly (P < 0.01) lower serum total osteocalcin (by 20% and 42%, respectively) and 25‐hydroxyvitamin D (by 37% and 42%, respectively), while serum parathyroid hormone levels were similar. In the combined patient group (n = 100), undercarboxylated osteocalcin was positively associated with bone markers. Conclusions Both Crohn's disease and ulcerative colitis patients have altered bone turnover relative to that in healthy controls.     

Fish oil and mental health: the role of n-3 long-chain polyunsaturated fatty acids in cognitive development and neurological disorders

Epidemiological and experimental studies have indicated that consumption of more n-3 long-chain polyunsaturated fatty acids may reduce the risk for a variety of diseases, including cardiovascular, neurological and immunological disorders, diabetes and cancer. This article focuses on the role of marine n-3 long-chain polyunsaturated fatty acids in brain functions, including the development of the central nervous system and neurological disorders. An overview of the major animal studies and clinical trials is provided here, focusing on fatty acid supplementation during pregnancy and infancy, and prevention and management of Alzheimer's disease, schizophrenia, depression and attention deficit hyperactive disorder. Although an optimal balance in n-3/n-6 long-chain polyunsaturated fatty acid ratio is important for proper neurodevelopment and cognitive functions, results from randomized controlled trials are controversial and do not confirm any useful effect of supplementation on development of preterm and term infants. The relationship between fatty acid status and mental disorders is confirmed by reduced levels of n-3 long-chain polyunsaturated fatty acids in erythrocyte membranes of patients with central nervous system disorders. Nevertheless, there are very little data supporting the use of fish oil in those patients. The only way to verify whether n-3 long-chain polyunsaturated fatty acids are a potential therapeutic option in the management and prevention of mental disorders is to conduct a large definitive randomized controlled trials similar to those required for the licensing of any new pharmacological treatment.     

The role of n-3 polyunsaturated fatty acids in the prevention and treatment of cardiovascular disease

Growing evidence has suggested an important role of n-3 polyunsaturated fatty acids in reducing risk of cardiovascular disease in the general population and patients with preexisting heart disease. In particular, several long-term epidemiologic studies have found an inverse association between fish consumption and risk of coronary heart disease or stroke. Two secondary prevention trials have found that increasing fish consumption or fish oil supplementation significantly reduced coronary death among patients with existing myocardial infarction. In addition, epidemiologic and clinical studies have suggested that alpha-linolenic acid (ALA), a short-chain n3-3 fatty acid from plant sources, may have similar cardiac benefits as long-chain n-3 fatty acids from fish. Potential mechanisms through which n-3 polyunsaturated fatty acids protect against CVD include their antiarrhythmic and antithrombotic effects, and improving insulin sensitivity and endothelial function. (c) 2001 Prous Science. All rights reserved.     

Role of GPR40 in pathogenesis and treatment of Alzheimer's disease and type 2 diabetic dementia

Abstract

G-protein coupled receptor 40 (GPR40) is also known as free fatty acid receptor 1. It is a typical 7 transmembrane receptor and currently the natural receptor of the saturated or unsaturated long-chain fatty acids. It could trigger the intracellular signalling pathway when combined with the free long-chain fatty acids, thereby controlling cells physiological function. In this review, we summarised the relationships and the potential mechanisms between the promising target GPR40, and pathogenesis and treatment of Alzheimer's disease and type 2 diabetic dementia. It may provide a theoretical reference for the development of clinical drug targeting GPR40.     

Altered long chain fatty acids composition in Duchenne muscular dystrophy erythrocytes

BACKGROUND: Biochemical abnormalities, increased efflux of soluble enzymes and muscle proteins, and altered permeability of muscle membranes imply the presence of a disorganized erythrocyte membrane in Duchenne muscular dystrophy (DMD). The purpose of the present study was to investigate this hypothesis of a generalized membrane defect. MATERIALS AND METHODS: Twenty-five patients with the disease were analyzed for their erythrocyte lipid composition and for alterations in their fatty acid content compared to twenty-five healthy subjects. RESULTS: DMD patients showed a decreased concentration of total phospholipids compared to healthy volunteers, with striking fluctuations in concentrations of erythrocyte long chain fatty acids. Specifically, the unsaturated fatty acids such as oleic, linoleic and arachidonic acids were significantly decreased in the disease, whereas the saturated fatty acid, palmitic acid was increased in DMD patients compared to healthy controls. CONCLUSION: Our findings suggest an abnormal fatty acid composition and disorganization of erythrocyte membrane in patients with DMD associated with possible functional alterations.     

The bleeding time effects of a single dose of aspirin in subjects receiving omega-3 fatty acid dietary supplementation

Dietary supplementation with omega-3 fatty acids reduces platelet aggregation in subjects who usually eat a diet low in these fatty acids. Aspirin also has an antiplatelet effect. The clinical effects of the concomitant administration of these agents were examined in this double-blind controlled crossover trial. Twelve healthy adults were randomized to supplement their diet for 21 days with 8 g of omega-3 fatty acids or identical-looking olive oil capsules. At the end of each treatment period, bleeding times were obtained before and after the administration of one 325-mg aspirin tablet. Overall, percent change in bleeding time after omega-3 fatty acid supplementation was significantly prolonged compared with olive oil supplementation before aspirin administration but not after. Bleeding times were influenced significantly by the order of randomization in the two treatment groups. Changes in post-aspirin bleeding time varied in subjects after they received olive oil. Post-aspirin bleeding times after omega-3 fatty acid supplementation were prolonged compared with baseline values but not significantly prolonged when compared with those after olive oil administration. The authors concluded that the concomitant administration of a single dose of aspirin does not prolong bleeding time in subjects who eat a diet enriched by omega-3 fatty acids versus a diet enriched by olive oil.     

Essential fatty acid status in paediatric Crohn's disease: relationship with disease activity and nutritional status

BACKGROUND: Active paediatric Crohn's disease is associated with nutritional deficiencies and altered nutrient intake. The availability of essential fatty acids (linoleic and alpha-linolenic acids) or their derivatives (arachidonic and eicosapentaenoic acids) may alter in plasma and cell membrane phospholipid in protein-energy malnutrition in children and in Crohn's disease in adults. AIM: To investigate the relationship of fatty acid phospholipid profiles with disease activity and nutritional status in paediatric Crohn's disease. METHODS: The fatty acid (proportionate) composition of plasma and erythrocyte phosphatidylcholine was determined in 30 patients (10.3-17.0 years) stratified into active and quiescent Crohn's disease (paediatric Crohn's disease activity index) and high and low body mass (body mass index centile). RESULTS: In plasma phosphatidylcholine, active disease activity was associated with a lower level of alpha-linolenic acid compared with that in quiescent disease (P < 0.05). A body mass index below the 50th centile was associated with active Crohn's disease, low linoleic and alpha-linolenic acids and high arachidonic acid (P < 0.05) in plasma phosphatidylcholine, and low alpha-linolenic acid in erythrocyte phosphatidylcholine. These findings could not be explained through differences in habitual dietary fat intake. CONCLUSION: In paediatric Crohn's disease, a low body mass index centile and high disease activity are associated with altered profiles of essential fatty acids and their derivatives, which may reflect altered metabolic demand.     

非诺贝特和辛伐他汀对酒精性脂肪肝血清游离脂肪酸谱的影响

目的　研究非诺贝特和辛伐他汀对酒精性脂肪肝大鼠模型血清游离脂肪酸谱的影响。方法　以酒精灌胃加橄榄油饮食的方法建立酒精性脂肪肝大鼠模型 ,模型组分为非诺贝特治疗组 (80mg·kg-1)、辛伐他汀治疗组 (4mg·kg-1)以及未治疗组。 4wk后处死大鼠 ,用气相色谱方法测定血清游离脂肪酸谱。结果　非诺贝特治疗组明显改善由乙醇引起的血清多不饱和脂肪酸的降低 [油酸 :(38 2 12± 7 788) μg·L-1vs (31 6 2 0± 6 14 2 ) μg·L-1,亚油酸 :(37 2 6 9± 8 0 6 5 ) μg·L-1vs (30 2 5 4± 9 0 6 3) μg·L-1,花生四烯酸 :(11 6 4 6±2 6 0 1) μg·L-1vs (9 0 12± 1 2 36 ) μg·L-1) ;同时肝脏病理改善。辛伐他汀治疗组则加重血清多不饱和脂肪酸的降低 ,并使饱和脂肪酸增加。结论　非诺贝特和辛伐他汀对酒精性脂肪肝血清游离脂肪酸谱作用不同 ;血清多不饱和脂肪酸在酒精性脂肪肝的发病机制以及治疗反应中可能起着重要的作用     

Prolonged n-3 polyunsaturated fatty acid supplementation ameliorates hepatic steatosis in patients with non-alcoholic fatty liver disease: a pilot study

BACKGROUND: Recent studies suggest a role of n-3 long-chain polyunsaturated fatty acids (n-3 PUFA) as peroxisome proliferator-activated receptor-alpha ligands in improving non-alcoholic fatty liver disease (NAFLD) in rodents. However, data in humans are still lacking. AIM: To evaluate the efficacy of prolonged PUFA supplementation in patients with NAFLD. METHODS: Fifty-six patients with NAFLD were enrolled. Among the overall eligible patients, 42 assumed n-3 PUFA 1-g capsule daily for 12 months, whereas 14 refused the treatment and were analysed as controls. All patients underwent haematochemical and ultrasound follow-up. RESULTS: Polyunsaturated fatty acid supplementation significantly decreased serum aspartate transaminase (P = 0.003), alanine transaminase (P = 0.002), gamma-glutamyl transpeptidase (P = 0.03), triglycerides (P = 0.02) and fasting glucose (P = 0.02) in comparison with controls. Circulating arachidonate and n-6/n-3 fatty acid ratio was reduced (P = 0.0002, and P = 0.0001 respectively) in treated patients. Moreover, ultrasonography demonstrated improvement of liver echotexture after PUFA (P = 0.0001), and increase of Doppler perfusion index (P = 0.001), whereas no significant changes occurred in controls. CONCLUSIONS: Supplementation with n-3 PUFA improves biochemical, ultrasonographic and haemodynamic features of liver steatosis. Our study supports the efficacy of n-3 PUFA as a new therapeutic approach in the treatment of NAFLD.     

Release of 5-ASA from Pentasa in patients with Crohn's disease of the small intestine

Background: Pentasa is a controlled-release tablet made from semipermeable microspheres and designed to continuously deliver therapeutic quantities of 5-ASA (5-aminosalicylic acid) throughout the gastrointestinal tract. Scintigraphic studies in healthy subjects have documented that 5-ASA release could occur in the small intestine. We tested here the disintegration of Pentasa in the digestive tract of nine patients with Crohn's disease of the small intestine. Materials: Each patient was given, after breakfast, a 250 mg tablet of Pentasa containing samarium-153 oxide. For 8 h the progression of the isotope in the gastrointestinal tract was followed using gamma camera scintigraphy. Plasma measurement of 5-ASA and acetylated 5-ASA was used to verify the liberation and absorption of 5-ASA. Results: The Pentasa tablet appeared completely dissolved in the stomach by 117 ± 18 min. Samarium oxide was first detected in the small intestine 60 ± 5 min after its ingestion; it reached the colon after 280 ± 13 min and it was completely absent from the small intestine at 360 ± 26 min. Plasma concentrations of 5-ASA started to rise after 67 ± 7 min and were maximal at 222±25 min. Conclusion: In patients with Crohn's disease of the small intestine, Pentasa microgranules start releasing 5-ASA in the proximal small intestine, acting locally to exert its beneficial effect.     

Quantitative Assessment of the Impact of Crohn's Disease on Protein Abundance of Human Intestinal Drug-Metabolising Enzymes and Transporters

Crohn's disease affects the mucosal layer of the intestine, predominantly ileum and colon segments, with the potential to affect the expression of intestinal enzymes and transporters, and consequently, oral drug bioavailability. We carried out a quantitative proteomic analysis of inflamed and non-inflamed ileum and colon tissues from Crohn's disease patients and healthy donors. Homogenates from samples in each group were pooled and protein abundance determined by liquid chromatography–mass spectrometry (LC-MS). In inflamed Crohn's ileum, CYP3A4, CYP20A1, CYP51A1, ADH1B, ALPI, FOM1, SULT1A2, SULT1B1 and ABCB7 showed ≥10-fold reduction in abundance compared with healthy baseline. By contrast, only MGST1 showed ≥10 fold reduction in inflamed colon. Ileal UGT1A1, MGST1, MGST2, and MAOA levels increased by ≥2 fold in Crohn's patients, while only ALPI showed ≥2 fold increase in the colon. Counter-intuitively, non-inflamed ileum had a higher magnitude of fold change than inflamed tissue when compared with healthy tissue. Marked but non-uniform alterations were observed in the expression of various enzymes and transporters in ileum and colon compared with healthy samples. Modelling will allow improved understanding of the variable effects of Crohn's disease on bioavailability of orally administered drugs.     

Dopamine D2 receptor as a novel target molecule for heart-type fatty acid binding protein

Essential roles of long-chain polyunsaturated fatty acids (LCPUFAs) have been documented in higher brain functions including emotion, learning and memory. Several clinical studies indicate that oral administration of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) can improve emotional and cognitive dysfunctions in schizophrenic patients. Likewise, arachidonic acid supplementation can improve cognitive dysfunction seen in human neurodegenerative disorders such as Alzheimer's disease. Since LCPUFAs are insoluble in an aqueous cellular environment, fatty acid binding proteins (FABPs) are essential to function as intracellular transport of LCPUFAs to appropriate intracellular compartments. Of various FABPs, heart-type fatty acid binding protein (H-FABP, FABP3) is highly expressed in neurons of mature brain. We previously demonstrated that H-FABP is associated with dopamine D2 receptor long isoform (D2LR) in vitro. Furthermore, we demonstrated that H-FABP knockout mice exhibit dopamine D2 receptor dysfunction. These results indicate that administration of LCPUFAs regulates dopamine D2 receptor functions through H-FABP in the brain.     

Studies on the mechanism of action of the hypoglycemic agent, 2-(3-methylcinnamylhydraznoo)-propionate (BM 42.304)

A new hypoglycemie agent, 2-(3-methylcinnamylhydrazono)-propionate MCHP (BM 42.304) was shown to be an inhibitor of the transfer of long-chain fatty acids across the mitochondrial inner membrane. The following data support this conclusion: the drug, at already 5 μM, inhibited ketogenesis from oleate but not from octanoate in the perfused guinea-pig liver; likewise, ketogenesis from l-(?)-palmitoylcarnitine and palmitoyl-CoA + l-(?)-carnitine, but not from octanoate, was depressed in isolated guinea-pig liver mitochondria. Oxigraphic measurements of the oxygen uptake by isolated mitochondria showed that the drug impaired oxygen uptake with the long-chain fatty acid derivatives but not with octanoate. Finally,in vivo effects of the drug such as hypoketonemia and an increased concentration of free fatty acids in blood are in agreement with the above formulated mechanism of action. A comment is given on the relationships between fatty acid oxidation and gluconeogenesis in the guinea-pig liver.     

Inhibition of long-chain acyl-CoA synthetase by the peroxisome proliferator perfluorodecanoic acid in rat hepatocytes

Perfluorodecanoic acid (PFDA) is a potent peroxisome proliferator and is known to affect hepatic lipid metabolism in rats. The effects of PFDA on fatty acid utilization were examined in isolated rat hepatocyte suspensions and in rat liver mitochondria and microsomes. PFDA inhibited the oxidation of palmitic acid but not octanoic or pyruvic acids when hepatocytes were incubated with 1 mM PFDA. At this PFDA concentration the esterification of palmitic acid into triacylglycerols was also reduced. The activity of long-chain acyl-CoA synthetase (ACS), an enzyme essential for both oxidation and esterification of fatty acids, was reduced in hepatocytes incubated with 1 mM PFDA. Carnitine palmitoyltransferase (CPT), an important enzyme for the oxidation of long-chain fatty acids, was not altered in hepatocytes incubated with this PFDA concentration. In rat liver mitochondria, palmitate oxidation and ACS activity were reduced significantly (P less than 0.01) at a PFDA concentration that had no effect on CPT activity. The inhibition of ACS by PFDA was similar in liver mitochondria and microsome preparations. In mitochondria incubated with PFDA, the inhibition of ACS appears to be noncompetitive for the substrates palmitic acid and CoA. However, the ACS inhibition by PFDA appeared to be competitive for the ATP binding site of the enzyme. Several chain length perfluorinated fatty acids were examined for their ability to inhibit mitochondrial ACS. Short-chain perfluorinated fatty acids (perfluoroproprionic and -butyric acid) did not inhibit ACS activity. However, medium-chain perfluorinated acids (perfluorooctanoic, -ananoic and -decanoic acid) were found to be potent inhibitors of ACS in isolated mitochondria. Whether ACS inhibition is causally related to PFDA-induced peroxisome proliferation and altered lipid metabolism seen in vivo is yet to be determined.     

儿童炎症性肠病微量营养素缺乏研究进展及治疗建议

炎症性肠病（IBD）是一种免疫相关的慢性肠道疾病,儿童患者占比约1/4。由于该症累及肠道,可影响营养元素的吸收,引起营养元素的缺乏。IBD患儿多见营养元素缺乏,由此可能影响IBD的发展及预后。故本文旨在总结与IBD并发症、疾病发展或结局有明确相关性的微量营养素,如并发症贫血（铁、叶酸、维生素B12）、骨病（钙、维生素D）、腹泻（锌和镁）。根据IBD患儿微量营养素缺乏治疗相关的最新文献,综合研究结果提供精准的药物治疗建议,推进儿童炎症性肠病的营养治疗。     

Nature and nurture in atherosclerosis: The roles of acylcarnitine and cell membrane-fatty acid intermediates

Macrophages recycle components of dead cells, including cell membranes. When quantities of lipids from cell membranes of dead cells exceed processing capacity, phospholipid and cholesterol debris accumulate as atheromas. Plasma lipid profiles, particularly HDL and LDL cholesterol, are important tools to monitor atherosclerosis risk. Membrane lipids are exported, as triglycerides or phospholipids, or as cholesterol or cholesterol esters, via lipoproteins for disposal, for re-use in cell membranes, or for fat storage. Alternative assays evaluate other aspects of lipid pathology. A key process underlying atherosclerosis is backup of macrophage fatty acid catabolism. This can be quantified by accumulation of acylcarnitine intermediates in extracellular fluid, a direct assay of adequacy of β-oxidation to deal with membrane fatty acid recycling. Further, membranes of somatic cells, such as red blood cells (RBC), incorporate fatty acids that reflect dietary intake. Changes in RBC lipid composition occur within days of ingesting modified fats. Since diets with high saturated fat content or artificial trans-fatty acids promote atherosclerosis, RBC lipid content shifts occur with atherosclerosis, and can show cellular adaptation to pathologically stiff membranes by increased long-chain doubly unsaturated fatty acid production. Additional metabolic changes with atherosclerosis of potential utility include inflammatory cytokine production, modified macrophage signaling pathways, and altered lipid-handling enzymes. Even after atherosclerotic lesions appear, approaches to minimize macrophage overload by reducing rate of fat metabolism are promising. These include preventive measures, and drugs including statins and the newer PCSK9 inhibitors. New cell-based biochemical and cytokine assays provide data to prevent or monitor atherosclerosis progression.     

INCREASED CONCENTRATION OF ARACHIDONIC ACID IN ERYTHROCYTE MEMBRANES IN CHRONICALLY LEAD-EXPOSED MEN

Animals intoxicated by lead present alterations in the fatty acid composition of red blood cells (RBC). Since this altered fatty acid com position of membranes may be a general reflection of lead toxicosis, we have examined 12 clinically healthy leadexposed male subjects for fatty acid composition of RBC membranes along with blood lead, serum calcium, and serum iron concentrations. Twelve unexposed age-matched male subjects were used as controls. Significantly increased levels of arachidonic acid (AA) were found as compared to matching healthy controls in the RBC of the leadexposed subjects. The increase of AA correlated in a dose-dependent manner with elevation in lead, and with serum iron, while a negative correlation was found between AA and serum calcium. The known ability of lead to substitute for calcium, which is essential in activating phospholipase A₂ for AA release from membrane phospholipids, may be the main reason for increased AA in RBC membranes.     

INCREASED BLOOD PRESSURE AND CHANGES IN MEMBRANE LIPIDS ASSOCIATED WITH CHRONIC ETHANOL TREATMENT OF RATS

1. Changes in membrane fluidity have been proposed to contribute to the pathogenesis of ethanol-induced hypertension possibly through changes in membrane lipid patterns, but reports are inconsistent. 2. In a controlled trial we documented ethanol-induced changes in blood pressure and composition of membrane lipids in ethanol-fed rats. 3. Systolic blood pressure increased significantly in the ethanol-treated rats (9.3 mmHg, s.e.m. 2.9) compared with the control group (—1.3 mmHg, s.e.m. 2.6). Mean cholesterol content in red cell membranes did not differ significantly between ethanol-fed and control rats. Phospholipids of aorta, red cells and kidney showed a significant decrease in the polyunsaturated to saturated fatty acid ratio, while membrane phospholipids from the heart showed a significant increase in the polyunsaturated to saturated fatty acid ratio with ethanol treatment. 4. In univariate regression blood pressure was significantly negatively related to levels of arachidonic acid in the kidney (P= 0.0013) and to linoleic acid in the aorta (P= 0.0341) and red cells (P= 0.0289). Blood pressure was not significantly related to fatty acids in the heart nor to membrane cholesterol or phospholipids. 5. Differences in fatty acid composition of phospholipids between controls and ethanol-fed rats are consistent with altered membrane fluidity. Altered membrane function is a potential mechanism involved in ethanol-induced hypertension.     

The effects of some antibiotics on polymorphonuclear leukocyte functions of elderly patients in vitro before and after zinc supplementation

The effects of ciprofloxacin, cefodizime, rifampicine, doxycycline and cefodizime + rifampicine combination on polymorphonuclear leukocyte (PMN) functions (phagocytosis and intracellular killing activity) were investigated in vitro in elderly patients and compared with those of healthy young volunteers before and after zinc supplementation. PMNs of 13 elderly hypertensive patients and 10 healthy young volunteers were isolated by Ficoll-Hypaque gradient centrifugation method from venous blood with EDTA. The subjects were given 22 mg/daily/oral zinc supplementation for 1 month. Serum zinc levels before and after supplementation were measured by flame atomic absorbtion spectrophotometer and the effects of each drug on PMN functions at therapeutic concentrations were investigated. Ciprofloxacin significantly increased the PMN's phagocytic activity of elderly patients (p = 0.002) before zinc supplementation and significantly increased both PMN functions of elderly patients (p = 0.002) after zinc supplementation. The same antibiotic significantly increased both PMN functions of healthy young volunteers (p = 0.005 and p<0.05, respectively) before and after zinc supplementation when compared with the control (drug-free). Cefodizime significantly increased the PMN's phagocytic activity of elderly patients (p = 0.003, p = 0.002) before and after zinc supplementation when compared with the control (drug-free). It also significantly increased both PMN functions of healthy young volunteers (p = 0.005 and p<0.05, respectively) before and after zinc supplementation when compared with the control (drug-free). Doxycycline significantly increased PMN's intracellular killing activity of healthy young volunteers before zinc supplementation (p<0.05) when compared with the control (drug-free) values. Rifampicine significantly decreased PMN's phagocytic activity of elderly patients (p<0.05) after zinc supplementation. Cefodizime+rifampicine combination significantly increased PMN's phagocytic activity at therapeutic concentrations of healthy young volunteers (p = 0.005) before zinc supplementation and PMN's phagocytic activity of elderly patients (p<0.05) after zinc supplementation when compared with the control (drug-free). Consequently, in the present study from the antibiotics ciprofloxacin, cefodizime and cefodizime + rifampicine combination, which are accepted as biological response modifiers have demonstrated stimulatory effects by significantly increasing polymorphonuclear leucocyte functions (phagocytosis and/or intracellular killing activity) of elderly patients and healthy young volunteers in vitro before and after zinc supplementation. Additionally zinc supplementation has more immunostimulatory effects on PMN functions of healthy young volunteers than elderly patients.