In vitro and in vivo effects of clindamycin on polymorphonuclear leukocyte function.

The effects of clindamycin on polymorphonuclear leukocytes (PMNLs) were evaluated in vitro and in vivo in an experimental model and in immunocompromised patients with and without infection. Chemotaxis, chemiluminescence, and bactericidal capacity were evaluated using PMNLs preincubated with clindamycin in different concentrations. In the three phases of the study, clindamycin at a concentration of 2 mg/L significantly increased PMNL function. In contrast, when higher concentrations were used, PMNL function was not modified and in some cases it was decreased. Our findings suggest that clindamycin, in concentrations of 2 mg/L, positively modifies PMNL function.     

The midterm (6 years) clinical results of the Carpenter-Edwards supra-annular bioprosthesis]

We present here the clinical results with a second-generation porcine bioprosthesis, the Carpentier-Edwards supra-annular valve (CESA). Two-hundred and twenty-two CESA bioprostheses were implanted in 189 patients during a four-year period (from 1984 to 1987), either as an isolated procedure or associated to mitral or tricuspid repair. The mid-term clinical results have been evaluated after a mean follow-up of 3.4 years, being 96% complete. There were 16 in-hospital deaths (8.4%) and 6 late, potentially valve-related, cardiac deaths (1.1% patients/year). Overall, 86.7 +/- 2% of the patients were free from cardiac death at 6 years (95.1 +/- 2% of the patients surviving the operative period). Linearized rates of valve related complications were the following: 1.4% patients/year for thromboembolism (including valve thrombosis), 0.5% patients/year for treatment-related hemorrhage and 0.7% patients/year for endocarditis. We did not found any case of either intrinsic or extrinsic valve failure, unrelated to infection of thrombosis. Two patients were reoperated, one because of valve thrombosis and the other due to prosthetic valve endocarditis (reoperation rate of 0.3% patients/year). When lethal and nonlethal valve-related complications (including in-hospital deaths) were considered all together, 75.8 +/- 8.4% of the patients remained alive and free of morbid events at 6 years. When patients were grouped according to the valve replaced (aortic, mitral and multiple), best results were found with patients submitted to isolated aortic valve replacement. We conclude that the CESA bioprosthesis has an excellent mid-term clinical performance. However, longer follow-up is necessary to know if improvement in valve design and manufacturing results in increased valve durability.     

Accumulation of brown adipose tissue and nutritional status. A prospective study of 366 consecutive autopsies.

Increased amounts of brown adipose tissue have been reported to occur in association with several diseases. The objective of the present study was to determine whether brown adipose tissue accumulation is related to nutritional status. Histologic sections of periadrenal tissue prospectively obtained at consecutive autopsies from 366 adults were examined. The cases were separated into three groups: malnourished (101 autopsies), normotrophic (128 autopsies), and obese (137 autopsies), according to the Quetelet index. Of these patients, 89 had brown adipose tissue accumulation, 35 were malnourished, 32 were normotrophic, and 22 were obese. The results showed a correlation between brown adipose tissue and patient nutritional status and a higher brown adipose tissue accumulation in malnourished patients. Cardiovascular disease was the most common type of illness present in the cases with brown adipose tissue accumulation.     

Antiplatelet activity of dipyridamole in non anticoagulated whole blood

Dipyridamole has been reported to inhibit platelet aggregation in citrate anticoagulated whole blood (WB). However, citrate may alter the response of platelets and/or the effect of antiplatelet drugs. The present study evaluates the "ex vivo" effect of dipyridamole, two hours after a single dose (3 mg/Kg) in 25 normal subjects in non-anticoagulated (native) WB and in WB anticoagulated with citrate or hirudin. We have used the BASIC anticoagulated with citrate or hirudin. We have used the BASIC wave as analytical method, which can evaluate the early steps of platelet activation with collagen in less than 1 min after venoclysis, thus allowing the study in native WB. The results show that dipyridamole significantly inhibits (p less than 0.001) platelet activation to collagen in citrated WB (66%) while the drug's effect is much lower (21%) and non-significant if evaluated in native or hirudine anticoagulated WB. These results suggest that citrate or low calcium concentration amplify the drug's platelet inhibitory action in WB and, therefore, the laboratory results may overestimate the drug's effect "in vivo".     

Adenosine administration produces an antidepressant-like effect in mice: evidence for the involvement of A1 and A2A receptors

This study investigated the effect of adenosine in the forced swimming test (FST) and the tail suspension test (TST) in mice, and the contribution of adenosine A1 and A2A receptors to adenosine's antidepressant-like effect. The immobility time in the FST was reduced by adenosine given either by i.p. (5-10 mg/kg) or i.c.v. (0.01-10 microg/site) route. Adenosine (1-10 mg/kg, i.p.) also produced an antidepressant-like effect in the TST. No treatment affected locomotion in an open-field. The anti-immobility effect of adenosine (10 mg/kg, i.p.) in the FST was prevented by i.p. pretreatment of mice with caffeine (3 mg/kg), DPCPX (2 mg/kg) and ZM241385 (1 mg/kg). CHA (0.05 mg/kg, i.p.) and DPMA (1-5 mg/kg, i.p.) also produced an antidepressant-like effect in the FST. This is the first report of an antidepressant-like effect of adenosine in mice, apparently mediated through an interaction with A1 and A2A receptors.     

HLA-B44 subtyping in a Spanish population: further evidence of Caucasian population diversity

HLA-B44 is the most frequent HLA-B allele in Caucasian populations. Several B44 subtypes, B*4402-B*4406, have been identified in individuals with this ethnic origin. Mismatches among B44 subtypes have been described as major targets for allogeneic responses in bone marrow transplantation. We have developed a PCR-SSO method, based on a B12- specific DNA amplification of exon 2 through exon 3 and subsequent non radioactive hybridization with eight probes, which allow us to discriminate all B12 homozygous combinations. We applied this method to determine the frequency of B44 subtypes in a Spanish population, as well as their HLA-A.-C.-DRB1,-DRB3/DRB4/DRB5.-DQA1 and -DQB1 associated haplotypes. A total of 141 healthy unrelated Spanish individuals and 31 B44-bearing haplotypes were investigated. Four B44 alleles were identified, B*4402 (33%), B*4403 (66%), B*4404 (0.7%), and B*4405 (0.7%). Haplotype analysis showed a clear differentiated distribution pattern for the two major B44 subtypes. B*4402 is associated with Cw5 (11/13) and A2 antigens (10/13). In contrast, B*4403 is mainly found together with DRB1*0701 (14/16). An inverted B*4402/B*4403 frequency in comparison with other European and North American Caucasian populations, revealed the existence of an extended haplotype diversity between populations of the same ethnic origin. Apart from anthropological studies, high resolution typing for HLA class I antigens presenting molecular polymorphism will be of great relevance in unrelated bone marrow transplantation.     

Angiotensin-(1–7) stimulates water transport in rat inner medullary collecting duct: evidence for involvement of vasopressin V2 receptors

The peptide angiotensin-(1–7) [Ang-(1–7)] is known to enhance water transport in rat inner medullary collecting duct (IMCD). The aim of this study was to determine the mechanism of the Ang-(1–7) effect on osmotic water permeability (P _f). P _f was measured in the normal rat IMCD perfused in vitro in presence of agonists [Ang-(1–7), arginine vasopressin (AVP) and Ang-(3–8)], and antagonists of the angiotensin and the vasopressin cascade. Ang-(1–7), but not Ang-(3–8), increased P _f significantly. The effect of Ang-(1–7) on P _f was abolished by its selective antagonist, A-779, added before or after Ang-(1–7). Prostaglandin E₂ and the protein kinase A inhibitor H8 also blocked the Ang-(1–7) effect. Blockade of vasopressin V₁ receptors by antagonists did not change the Ang-(1–7) effect, but pre-treatment with a V₂ antagonist abolished the effect of Ang-(1–7) on P _f. Similarly, pre-treatment with A-779 inhibited AVPs effect on P _f. Forskolin-stimulated P _f was blocked both by A-779 and by the V₂ antagonist. Finally, Ang-(1–7) increased cAMP levels in fresh IMCD cell suspensions whilst the forskolin-stimulated cAMP synthesis was decreased by A-779 and the V₂ antagonist. These data provide evidence that Ang-(1–7) interacts via its receptor with the AVP V₂ system through a mechanism involving adenylate-cyclase activation.