Adult stem cells: Early clinical trials and perspective

Cardiac repair with cell-based therapy is a promising treatment for patients with coronary heart disease. Preclinical and early clinical studies have shown that stem cell therapy is safe and effective in improving left ventricular function and myocardial perfusion. Specifically, cardiac stem cell therapy may be beneficial in reducing left ventricular remodeling in patients with myocardial infarction and in improving symptoms and preventing cardiac enlargement in patients with chronic ischemic heart disease. Although not well defined, multiple mechanisms, including paracrine effects, probably contribute to stem cell-mediated cardiac repair. The issues of timing, mode of delivery, and cell dose need to be systematically studied to maximize benefits. Nevertheless, rapid advancements may soon make cardiac stem cell therapy a central part of the treatment regimen for patients with coronary heart disease.     

Differentiation of Mycobacterium tuberculosis from other mycobacteria with rho-nitrobenzoic acid using MGIT960.

SETTING: Mycobacteria growth in media with the addition of inhibitory substances has been used in species identification. Growth of the Mycobacterium tuberculosis complex (MTC) is inhibited by rho-nitrobenzoic acid (PNB), whereas non-tuberculous mycobacteria (NTM) are resistant. OBJECTIVE: To develop a rapid PNB test using the automated BACTEC MGIT960 system and to evaluate its usefulness in the screening of mycobacterial isolates. DESIGN: PNB tests were performed in 93 MTC strains and 61 NTM strains from the Instituto Adolfo Lutz Culture Collection. PNB was added to L?wenstein-Jensen (LJ) medium and to BACTEC MGIT960 medium. RESULTS: The MTC strains were all PNB-susceptible, confirming the original identification. Among 10 NTM species, all were found to be resistant to PNB, except for one strain of M. kansasii and another of M. marinum. The median time to obtain presumptive identification of MTC by inhibition test in the BACTEC MGIT960 system was 6.3 days and for NTM it was 2.5 days. The presumptive identification of MTC in LJ was mostly obtained after day 20. CONCLUSION: The key finding of this analysis was the possibility of combining the traditionally accepted method proposed by Tsukamura and Tsukamura in 1964 with the modern, safe and rapid BACTEC MGIT960 methodology.     

Long-term left ventricular pacing

A 57-year-old female was implanted with a Biotronik Pikos VVI pulse generator. During her follow-up period right bundle-branch block was observed. Therefore further posteroanterior and lateral chest X-ray and echocardiography were performed. Only the transoesophageal echocardiography showed exactly the abnormal pathway of the electrode through the foramen ovale apertum to the left side of the heart. Abnormal electrode position can create serious complications, however, our patient remained free of symptoms throughout her 5 year follow-up.     

Changes in the isoenzyme and kinetoplast DNA patterns of Trypanosoma cruzi strains induced by maintenance in mice

Culture forms of thirteen Trypanosoma cruzi strains from 4 zymodemes and 9 schizodemes were inoculated and kept by successive passages in C3H mice. The strains were initially from the following zymodemes: 3 from A, 3 from B, 4 from C and 2 from D and 1 from AB mixed zymodemes. After approximately 18 months maintenance the parasites were isolated by hemoculture and again typed according to their isoenzyme and kinetoplast DNA patterns. The zymodeme A strains kept their initial patterns; from the 3 zymodeme B strains, two kept the initial patterns and one changed to zymodeme A; from the 4 zymodeme C, two kept the initial pattern and two changed to zymodeme B; from the 2 zymodeme D strains, one kept the initial pattern and one changed to zymodeme A. The strain from AB mixed zymodeme was reduced to zymodeme. A. The zymodeme changes were accompanied by schizodeme changes. Although not simultaneously, in one T. cruzi strain the parasitemia change was followed by zymodeme and schizodeme changes. The results showed that prolonged maintenance of T. cruzi in mice by successive passages alters the isoenzyme and k-DNA patterns of some strains and that these alterations tend to move towards zymodeme A, suggesting a selective effect of mice over these T. cruzi populations.     

Detection of Toxoplasma gondii soluble antigen, SAG-1(p30), antibody and immune complex in the cerebrospinal fluid of HIV positive or negative individuals

Active infection by T. gondii was evaluated by immunoassay for soluble SAG-1 (p30), the major surface antigen from T. gondii, specific antibodies and immune complexes in human cerebrospinal fluid (CSF) samples. A total of 263 samples of CSF were collected from hospitalized patients presenting neurological disorders and analyzed for antibodies to HIV. Patients were divided into two groups: HIV positive (n = 96) or HIV negative (n =167). The results of the assays showed that 45% of all samples were positive for soluble SAG-1. Toxoplasma Ag/Ab immune complexes were detected in 19% of the CSF samples and 62% were positive for T. gondii- specific IgG. A combination of these assays in the presence of clinical findings consistent with active Toxoplasma infection may predict the presence of toxoplasmic encephalitis. Moreover, detection of soluble SAG-1 in the CSF of these individuals appears consistent with active infection.     

Experimental leptospirosis in marmoset monkeys (Callithrix jacchus): a new model for studies of severe pulmonary leptospirosis

Experimental infection of marmoset monkeys (Callithrix jacchus) with Leptospira interrogans serovar Copenhageni showed microscopic patterns of tissue reactions comparable to those seen in the severe forms of human leptospirosis, including intra-alveolar hemorrhage. The most impressive microscopic changes were seen in the lung and kidney of animals killed at days 6 and 12 after inoculation. There were extensive and irregular areas of hemorrhage predominating around main bronchial branches or diffusely spread to the pulmonary parenchyma, as well as severe tubulointerstitial nephritis. Antibody response detected by the microscopic agglutination test was quantitatively similar to those seen in humans and paralleled severity of tissue lesions. The distribution of leptospires or antigenic debris in infected tissues was observed by immunofluorescence and confocal laser scanning microscopy. Large numbers of typical leptospires were seen in the lumen of proximal renal tubules. Positive reactions showing antigenic debris were closely associated with sites of tissue damage.     

Late coronary artery recanalization effects on left ventricular remodelling and contractility by magnetic resonance imaging.

AIMS: To assess the recanalization effects of post-myocardial infarction (MI) on left ventricular (LV) remodelling and contractility in relation to conservative therapy. METHODS AND RESULTS: Thirty-six patients with occluded infarct-related artery between 12 h and 14 days post-anterior MI were randomized to percutaneous coronary intervention (PCI group) or conservative therapy (no-PCI group). Magnetic resonance imaging was performed at enrollment and after 6 months. The left ventricle was divided into infarct, adjacent, and remote segments. There was no difference in relation to LV volume between groups at the 6 month follow-up. Change in LV ejection fraction was favourable to the PCI group: 5.00% vs. -0.76%, P=0.012. Change in circumferential shortening (Ecc) of the remote segments in the PCI group was significantly better than in the no-PCI group: -1.67+/-6.30% vs. 0.29+/-6.02%, P<0.001. Infarct size and LV mass were similar between groups. CONCLUSIONS: Late recanalization improved LV ejection fraction and myocardial contractility in late follow-up, but did not change the ventricular volumes. Improvement in the left ventricle global and regional contractility may benefit the long-term outcome in post-MI patients with sustained patency of the infarct-related artery.     

Changes in distribution spaces and cell permeability caused by ATP in the rat liver

AIMS/BACKGROUND: Cellular and extracellular volume changes caused by ATP were investigated in the liver as well as the possible formation of diffusion barriers, which could be responsible for some of its metabolic effects. METHODS: The experimental system was the bivascularly perfused rat liver. [(14)C]Sucrose and [(3)H]water were simultaneously injected into either the portal vein or the hepatic artery. Mean transit times, distribution spaces, variances and linear superimpositions were calculated. RESULTS: In the portal system, ATP reduced the transit time in the great vessels, had little or no effect on sinusoidal and cellular spaces, but impaired the flow-limited distribution of both [(14)C]sucrose and [(3)H]water. In the arterial bed ATP infused into either the portal vein or the hepatic artery produced vasodilation and increased the aqueous extra-sucrose space. These effects were inhibited by Nomega-nitro-L-arginine methyl ester infused into the hepatic artery. CONCLUSIONS: Sucrose and extra-sucrose space changes caused in the arterial bed by portally infused ATP are most probably analogous to the transhepatic vasodilation effect already described for the rabbit liver. Impairment of flow-limited distribution of tracers in the sinusoidal bed indicates that ATP induces the formation of permeability barriers, which could be responsible for some of its metabolic effects.     

The first record of American visceral leishmaniasis in domestic cats from Rio de Janeiro, Brazil

This paper is the first to report visceral leishmaniasis in domestic cats (Felis catus domesticus) from an endemic area in Rio de Janeiro state, Brazil. A relatively high seroprevalence of 25% was observed although none of them have presented any symptom. Our results support the observation of previous authors, suggesting that cats may be considered as alternative domestic hosts of visceral leishmaniasis and should be included in serological investigations performed in endemic areas.     

Geographical patterns of allelic diversity in the Plasmodium falciparum malaria-vaccine candidate, merozoite surface protein-2

The polymorphic merozoite surface protein-2 (MSP-2) of Plasmodium falciparum is a major malaria-vaccine candidate. In the present study, PCR and hybridization with allelic-specific probes were used to type the Msp-2 gene from isolates from hypo-endemic Brazil (N = 113), meso-endemic Vietnam (N = 208) and holo-endemic Tanzania (N = 67). The typing methods were designed to group isolates into the dimorphic allelic families FC27 and IC1 and to detect possible between-family recombination events. The analysis was complemented by a comparison of 156 Msp-2 sequences from the GenBank database with 12 additional sequences obtained during the present study. Statistically significant differences were detected in pair-wise comparisons of the distribution of Msp-2 allelic types in Brazil and Vietnam, and in Brazil and Tanzania, but not in Vietnam and Tanzania. The extent of allelic diversity in the Msp-2 gene, as estimated by the total number of different alleles found in a given parasite population and the mean multiplicity of infections, clearly paralleled the levels of malaria endemicity in the study areas. However, no correlation between age and multiplicity of infections was found in the subjects. The patterns of Msp-2 diversity in Brazil appeared to be temporally stable, since no significant difference was observed in the distribution of Msp-2 allelic types among isolates collected, 10--13 years apart, in the same area of Rond?nia. Despite the extensive sequence diversity found in Msp-2 alleles, especially in the central repetitive region of the molecule, several instances of identical or nearly identical alleles were found among isolates from different countries and regions, possibly as a result of extensive homoplasy. No recombinant allele was detected by molecular typing in any of the study sites, and the GenBank database included only 12 recombinant sequences (representing 7% of all reported Msp-2 sequences), all of them with an IC1-type 5' end and an FC27-type 3' end. A single, putative, crossover site was characterised for all recombinant alleles. Most of the allelic diversity observed was therefore attributable to variation in the repetitive region of the gene, instead of recombination between alleles of dimorphic families (as commonly found, for example, in the Msp-1 gene). The implications of these findings for studies on the genetic and antigenic diversity of malarial parasites are discussed.