Circulating interleukin 6 levels, blood pressure, and insulin sensitivity in apparently healthy men and women.

There is increasing evidence that systemic inflammation and insulin resistance constitute interrelated events that contribute to atherosclerosis. We studied the effect of the association between circulating interleukin 6 (IL-6) levels, one of the major mediators of inflammation, and C-reactive protein on insulin resistance and blood pressure in 228 healthy volunteers. The plasma IL-6 concentration was significantly and similarly associated with systolic (SBP) and diastolic (DBP) blood pressure, fasting insulin, and the fasting insulin resistance index (FIRI) in all subjects. When smokers were excluded from the analysis, plasma IL-6 levels correlated with percent fat mass (r = 0.19; P = 0.02), absolute fat mass (r = 0.17; P = 0.03), SBP, DBP, fasting insulin levels, and FIRI. The latter associations persisted after controlling for body mass index (r = 0.15 and r = 0.19; P = 0.02 and P: = 0.0004 for SBP and DBP, respectively; r = 0.24 and r = 0.19, P = 0.004 and P = 0.03, for fasting insulin and FIRI, respectively). Gender and smoking status significantly influenced the results. Although IL-6 levels were significantly associated with fasting insulin and FIRI in men, these significant correlations were not observed in women. Conversely, although IL-6 levels were significantly associated with SBP and DBP in women, these coefficients were not statistically significant in men. All of these associations were lost among smokers and remained significant in nonsmokers. As IL-6 is the major mediator of the acute phase response by hepatocytes and induces the synthesis of C-reactive protein (CRP), we also controlled for the latter. Serum CRP levels correlated significantly with IL-6 in all the subjects, but mainly in nonsmokers and men. Of note was that this significant relationship was lost among smokers. CRP was associated with fasting insulin (r = 0.28; P < 0.0001) and FIRI (r = 0.25; P < 0.0001), but not with SBP or DBP (P = NS), in all subjects. Unlike IL-6, the associations between CRP and these parameters were similar in men and women and in smokers and nonsmokers. For insulin and FIRI they were stronger in women and in nonsmokers. CPR significantly correlated with the WHR only in men (r = 0.22; P = 0.01). Using multiple linear regression in a stepwise manner to predict circulating IL-6 levels, smoking status (P = 0.0059) and FIRI (P = 0.03), but not fat mass or SBP, independently contributed to 11% of its variance in men. When CRP was introduced into the model, the latter (P < 0.0001) and smoking status (P = 0.02), but not FIRI, fat mass, or SBP, contributed to 33% of the variance in IL-6 levels. In women, only SBP (P = 0.04) contributed to 5% of its variance. When CRP was introduced into the model, again only SBP (P = 0.01) contributed to 10% of the variance in IL-6 levels. In 25 of these subjects, insulin sensitivity was determined using the frequently sampled iv glucose tolerance test with minimal model analysis, and circulating IL-6 levels were strongly associated with the insulin sensitivity index (r = -0.65; P < 0.0001). Again, this relationship was even stronger in men (r = -0.75; P < 0.001) and was not significant in women (r = -0.26; P = NS). In all of these subjects, only insulin sensitivity (P = 0.0037), not fat mass, contributed to 21% of the variance of IL-6 levels in a multiple linear regression analysis. In summary, circulating IL-6 levels, by inducing either hypertension in women or insulin resistance in men, constitute a significant proatherogenic cytokine. The mechanisms of these associations should be further investigated.

The fat-free mass compartment influences serum leptin in men.

OBJECTIVE: Recent experimental work in mice has demonstrated that leptin is synthesized by muscle cells. As this latter tissue is the main target for insulin-estimulated glucose disposal, we hypothesized that the muscular and fat-free mass (FFM) compartments might influence serum leptin levels in humans through increased insulin resistance. DESIGN AND METHODS: We evaluated body composition (through bioelectric impedance and anthropometrical parameters), insulin resistance (using the fasting insulin resistance index (FIRI) and insulin sensitivity (S(I)) from the minimal model analysis) and leptin levels in 140 men and 114 women. RESULTS: Serum insulin, FIRI and leptin levels were significantly increased in men in the highest quintile of FFM. Leptin levels positively correlated with FFM in men (r=0.24, P=0004) but not in women (r=0.02, P=not significant). With weight gain, however, approximately 25% of the additional weight is lean mass, so that obese people have higher fat-free mass than lean people. Hence, we performed a multiple linear regression analysis in a stepwise manner to predict leptin levels, in which fat mass (FM), FFM, and FIRI, but not age or waist-to-hip ratio (WHR) independently contributed to 32%, 6% and 3% of the variance in serum leptin levels in men. In women, FM (49%), FIRI (3.6%) and WHR (2.4%), but not FFM or age explained this variance. In a sample of 40 subjects, S(I) and leptin correlated with mid-arm muscle circumference (r=-0.51, P=0.03 and r=0.53, P=0.02) and mid-arm muscle area (r=-0.52, P=0.03 and r=0.53, P=0.02) in men (n=17) but not in women (n=23). CONCLUSIONS: The fat-free mass compartment contributes to the variability of serum leptin levels in men. Whether insulin resistance at this level mediates an increased production of leptin merits further research.

Circulating granulocyte-macrophage colony-stimulating factor and serum fatty acid composition in men and women.

Atherosclerosis is increasingly recognized as an inflammatory disease. Granulocyte-macrophage colony-stimulating factor (GM-CSF) is a proinflammatory cytokine, recently implicated as a prominent component of the regulatory network involved in atherogenesis. We aimed to study the relationship between circulating GM-CSF levels and serum fatty acid (FA) composition in 78 healthy subjects. The latter was analyzed by gas-liquid chromatography and GM-CSF by a high-sensitivity commercial enzyme-linked immunosorbent assay (ELISA). Among women (n = 40), serum GM-CSF levels were found to be positively associated with the proportion of palmitic acid (C16:0) and negatively with linoleic acid (C18:2omega-6), docosahexaenoic acid (DHA, C22:6omega-3), and the proportion of total essential FA. After excluding smoking women (n = 6), the associations among GM-CSF and serum linoleic acid concentration (r = -0.49, P =.003), arachidonic acid (r = -0.52, P =.001), and DHA (r = -0.34, P =.04) were strengthened. The ratio of palmitic to linoleic and DHA acids was the single best predictor of serum GM-CSF in all subjects. Together with arachidonic acid, it contributed to 22% of the GM-CSF variance in women, after taking into account the effects of age, body mass index (BMI), blood pressure, and smoking status. None of these associations were observed among men. In conclusion, serum FA composition is associated with circulating GM-CSF specifically in women. As human arterial and venous smooth muscle cells release GM-CSF, and treatment of endothelial cells with oxidized low-density lipoproteins results in a rapid expression of GM-CSF, the mechanisms involved in these associations and the sex-linked differences should be further explored.

Efficacy of an inactivated vaccine for prevention of reproductive failure induced by porcine reproductive and respiratory syndrome virus.

This report describes the results of experiments with an inactivated oily vaccine containing per dose about 10(5.5) median tissue culture infectious dose (TCID50) of the Spanish strain of porcine reproductive and respiratory syndrome (PRRS) virus grown in porcine alveolar macrophages (PAMs). In order to evaluate the efficacy of the vaccine, two experimental infection routes were tested in sows; subsequent intranasal (i.n.) and intravenous (i.v.) (out of a total of 93 piglets born to 7 sows, 16% were mummified, 18.2% were weak and died within 48 h of birth, 37% were stillborn, 5.3% died between 2 and 7 days of age, 22.5% lived for more than one week) and intranasal alone (out of a total of 65 piglets born to 5 sows, 0% were mummified, 22.5% were weak and died within 48 h of birth, 40% were stillborn, 4.6% lived for more than one week). I.N. alone was selected to evaluate the efficacy of the vaccine because this is the natural route of infection. A number of experiments were conducted to test the immunogenicity of the vaccine. In general, after challenge with the homologous strain, protection in vaccinated sows was high (at least 70% of the piglets were born alive and healthy), whereas protection in unvaccinated sows was low (only 10% of the piglets were born alive and healthy). Vaccinated animals devoid of antibodies by immunoperoxidase monolayer assay (IPMA) at the time of challenge were still protected at experimental infection.

Porcine epidemic abortion and respiratory syndrome (mystery swine disease). Isolation in Spain of the causative agent and experimental reproduction of the disease.

In March of 1991, a disease that affected pregnant sows and caused a high mortality in unweaned piglets was detected in Spain. Based on the clinical signs observed, mystery swine disease, which had been described recently in Germany, Holland and Belgium, was suspected. From the samples obtained from the affected farm, a filtrable agent (0.22 micron) was isolated on cell culture. It produced cytopathic effects, its replication was intracytoplasmic, it was sensitive to chloroform, and cross-reacted with a Lelystad reference serum. When inoculated into pregnant sows, the agent produced inappetence for 2-4 days, without hyperthermia. One of the sows aborted at 100 days of gestation; the two others had delayed parturitions (days 115 and 116). There was a mixture of healthy piglets, mummified fetuses, stillbirths and weak piglets. Microscopic examination of the lungs of healthy piglets killed at 8 and 12 days of life revealed the presence of interstitial pneumonia. The sera from the three sows at 39 days after infection cross-reacted with the Lelystad virus (titres > or = 1/640), whereas pre-inoculation sera did not recognize it (titres < or = 1/10). This is the first report from Spain of the isolation of an agent (antigenically related to the Lelystad virus), capable of reproducing the disease previously designated as mystery swine disease.

[Body mass index (BMI) and percent fat mass. A BMI > 27.5 kg/m2 could be indicative of obesity in the Spanish population]. / Indice de masa corporal (IMC) y porcentaje de masa grasa: un IMC mayor de 27,5 kg/m2 podría suponer obesidad en la población española.

BACKGROUND: The World Health Organization (WHO) defines obesity as a condition of excessive fat accumulation to the extent that health and well-being are affected. For population studies, the measurement of weight, corrected for height, is still the method of choice (BMI). In Caucasian populations, the BMI cut-off point for obesity (30 kg/m2) corresponds with a percent body fat (PFM) of over 25% in young adult males and 35% in young adult females. However, the relation between BMI and PFM is not uniform among populations. It is important to define in each population the threshold of BMI which corresponds to the definition of obesity. PATIENTS AND METHOD: BMI was calculated in 282 subjects. PFM was analyzed using Bio-electrical impedance. Blood pressure, serum glucose and insulin, and the fasting insulin resistance index were also determined in all subjects to analyze the metabolic impact. RESULTS: The PFM of 25% in males and 35% in females corresponded to a BMI of 27.5 and 27.4 kg/m2, respectively. The slope of the relationship between the degree of obesity and comorbilities (insulinemia, fasting insulin resistance index and blood pressure) was strengthened above 26 kg/m2 in men and 24 kg/m2 in women. CONCLUSIONS: BMI that corresponds to a PFM previously defined as obesity is lower in our population in comparison with other Caucasian populations. Our results confirm that is impossible to compare the prevalence of obesity among populations using exclusively the BMI. It will be important to define, using reference methods, whether these findings have physiological impact or not, and if this cut-off of BMI determines an increment in cardiovascular and overall mortality using epidemiological approaches.

Study of carbendazin residue accumulation on greenhouse and field-grown strawberries, after successive treatments with benomyl.

Benomyl, a systemic fungicide used in preharvest treatments to prevent Botrytis and other fungal diseases, metabolizes to carbendazim (MBC). A study was undertaken to determine if the total residues of MBC of greenhouse and field-grown Douglas strawberries accumulate in fruits after successive fortnightly treatments with a commercial preparation of benomyl. Statistical analysis of the data obtained indicates that residues of MBC do not accumulate in fruits; on the contrary, they decrease over time.

Monitoring residues of carbendazim (applied as benomyl) and thiabendazole in Wellspur apples.

Residues of benomyl (determined as carbendazim, widely accepted as MBC) and of thiabendazole in Wellspur apples were monitored after the apples were treated postharvest by immersion in a bath with each of the fungicides separately and stored under refrigeration. Whole fruit and pulp analyses were conducted over the period beginning 1 day after treatment and lasting up to 200 days afterwards. Under the conditions described, both benomyl (expressed as parts per million of carbendazim) and thiabendazole were found in the fruits in the following average amounts: 0.44 +/- 0.03 and 0.11 +/- 0.03 ppm benomyl (as carbendazim) in whole fruit and in pulp, respectively; 0.98 +/- 0.10 and 0.39 +/- 0.10 ppm thiabendazole in whole fruit and in pulp, respectively.