Induction of apoptosis of human primary osteoclasts treated with extracts from the medicinal plant <Emphasis Type="Italic">Emblica officinalis</Emphasis>

Background  

Osteoclasts (OCs) are involved in rheumatoid arthritis and in several pathologies associated with bone loss. Recent results support the concept that some medicinal plants and derived natural products are of great interest for developing therapeutic strategies against bone disorders, including rheumatoid arthritis and osteoporosis. In this study we determined whether extracts of Emblica officinalis fruits display activity of possible interest for the treatment of rheumatoid arthritis and osteoporosis by activating programmed cell death of human primary osteoclasts.     

Effects of tryptophan depletion on central and peripheral chemoreflexes in man

Klein (Arch. Gen. Psychiatry 50, 306-317, 1993) suggests that panic attacks are the result of a defective 'suffocation alarm' threshold that presents with carbon dioxide (CO(2)) hypersensitivity, exaggerated ventilatory response and panic in panic disorder (PD) patients. Serotonergic deficiencies enhance this ventilatory response in PD patients, as per 'suffocation alarm' theory predictions, suggesting that serotonin (5-HT) normalizes the ventilatory response. Other research supports a serotonin system-mediated stimulation of ventilation. Knowledge of 5-HT's role on ventilatory output and its neurophysiological sources impacts on the 'suffocation alarm' theory validity and predictive value. We used tryptophan depletion (TRP-) in concert with a modified Read rebreathing test to determine the effect of deficient serotonergic modulation on the central and peripheral chemoreflex threshold and sensitivity of response to CO(2) in 11 healthy men. TRP- did not affect central or peripheral chemoreflex threshold or sensitivity of response to CO(2). However, basal ventilation was significantly elevated during TRP-. In contrast to 'suffocation alarm' theory predictions, decreased 5-HT neurotransmission does not significantly affect the respiratory chemoreflex response to CO(2), impacting on non-chemoreflex drives to breathe. Panic associated respiratory abnormalities may be related to defective 5-HT modulation of non-chemoreflex drives to breathe, unrelated to any respiratory chemoreflex abnormality.     

Proteomic and postproteomic characterization of keratan sulfate-glycanated isoforms of thyroglobulin and transferrin uniquely elaborated by papillary thyroid carcinomas

Previous studies have suggested that surface components of papillary thyroid carcinoma (PTC) cells may be aberrantly glycanated, but the precise nature of these molecules has not been unveiled nor documented to be of clinical relevance. A monoclonal antibody was raised against a unique keratan sulfate (KS) determinant and used to differentially screen benign and malignant thyroid tissue for the expression of components carrying these moieties. In a total of 349 cases of benign and malignant thyroid lesions, 100% of the 115 PTC cases examined (including various histological subtypes) were found to contain KS-bearing molecules, whereas these were virtually absent from benign tissues and other thyroid tumors, with the exception of 21% of the follicular carcinoma cases analyzed. A composite immunoaffinity chromatography, immunochemistry, and mass spectrometric approach revealed that the PTC-specific KS-bearing macromolecules were unique glycoforms of thyroglobulin and transferrin. Combined, reciprocal immunoprecipitation and Western blotting further indicated that the former glycoform predominated and that most of the transferrin produced by PTC was glycanated with KS moieties. Fluorescent keratanase II-based fingerprinting of the KS moieties bound to these isoforms further demonstrated several PTC-specific peculiarities: 1) that a considerable portion of the moieties was covalently attached via a novel core protein linkage structure; 2) they had an unusual extended average length; 3) an unusual relative ratio of highly sulfated disaccharides terminating with alpha (2-3)-linked N-acetylneuraminic acid capping residues; and 4) a novel unidentified oligosaccharide moiety at the nonreducing terminus. Comparative analysis of the relative distribution of transferrin in benign versus PTC tissues highlighted a marked malignancy-associated abundance of the molecule, with a >75% frequency in expression in PTC. These findings demonstrate that PTC cells synthesize unique post-translationally modified thyroglobulin and transferrin variants in situ that may be directly exploitable for diagnosis, through histological and noninvasive cytological procedures; for devising novel strategies for antibody-guided imaging of this tumor in vivo; and for postsurgery follow-up of PTC patients.     

Six-month multicenter study on invasive infections due to Streptococcus pyogenes and Streptococcus dysgalactiae subsp. equisimilis in Argentina

During a 6-month period, 95 invasive infections due to Streptococcus pyogenes and group C or group G Streptococcus dysgalactiae subsp. equisimilis were recorded from 40 centers of 16 cities in Argentina. We describe here epidemiologic data available for 55 and 19 patients, respectively, associated with invasive infections due to S. pyogenes and S. dysgalactiae subsp. equisimilis. The associated isolates and 58 additional pharyngeal isolates were genotyped and subjected to serologic and/or antibiotic susceptibility testing. Group A streptococcal emm type distribution and strain association with toxic shock appeared to differ somewhat from results found within the United States; however, serologic characterization and sof sequence typing suggested that emm types found in both countries are reflective of shared clonal types.     

Haemophilus influenzae type b infection in childhood: history of bacteremia and antigenemia.

Groups of children (mean age, 31.4 months) with Haemophilus influenzae type b meningitis, epiglottitis, or septic arthritis were tested for the presence and levels of bacteremia, capsular polyribophosphate (PRP) antigenemia, and development of specific antibody in serum after the onset of acute illness. Although bacteremia cleared promptly after antibiotic therapy, circulating PRP could be detected in serum for relatively long periods, with 51% of the patients still having detectable antigen after 30 days postinfection. Even in the presence of specific antibody, antigenemia persisted for as long as 47 days after admission. It was observed that there was no statistically significant correlation between the persistence of antigenemia and age (P greater than 0.2), the initial antigen concentration (P greater than 0.50), or the development of antibody (P greater than 0.20). The presence of a low magnitude of bacteremia (less than 300 organisms per ml) was associated with a maximum concentration of 10 ng of PRP per ml. On the other hand, bacterial counts in excess of 10(4)/ml were associated with greater than 1,000 ng of PRP per ml (r = 0.98, r2 = 0.96, P less than 0.001). It was observed that the amount of circulating PRP in the acute phase of illness was related to whether a child developed convalescent-phase antibody. Invariably, the younger children, who primarily had meningitis, had a PRP concentration of greater than 10 ng/ml and failed to develop an antibody response in any isotype, whereas the older patients, who primarily had infections other than meningitis, had a PRP concentration of less than 10 ng/ml and a 45.5% success rate in developing an antibody response (P = 0.006). These findings suggest that there is a direct correlation between the magnitudes of bacteremia and antigenemia, that antigen may persist for long periods even in the presence of antibody, and that the level of antigenemia in addition to the patient age is significantly related to the nature of the convalescent-phase antibody response.     

Prevalences, genotypes, and risk factors for HIV transmission in South America

HIV cross-sectional studies were conducted among high-risk populations in 9 countries of South America. Enzyme-linked immunosorbent assay screening and Western blot confirmatory testing were performed, and env heteroduplex mobility assay genotyping and DNA sequencing were performed on a subset of HIV-positive subjects. HIV prevalences were highest among men who have sex with men (MSM; 2.0%-27.8%) and were found to be associated with multiple partners, noninjection drug use (non-IDU), and sexually transmitted infections (STIs). By comparison, much lower prevalences were noted among female commercial sex workers (FCSWs; 0%-6.3%) and were associated mainly with a prior IDU and STI history. Env subtype B predominated among MSM throughout the region (more than 90% of strains), whereas env subtype F predominated among FCSWs in Argentina and male commercial sex workers in Uruguay (more than 50% of strains). A renewed effort in controlling STIs, especially among MSM groups, could significantly lessen the impact of the HIV epidemic in South America.     

Semantic relatedness effects in conjoined noun phrase production: implications for the role of short-term memory

Speech error data and empirical studies suggest that the scope of planning is larger for semantic than for phonological form representations in speech production. Previous results have demonstrated that some patients show dissociable impairments in the retention of semantic and phonological codes. The effect of these STM deficits on speech production was investigated using a phrase production paradigm that manipulated the semantic relatedness of the words in the phrase. Subjects produced a conjoined noun phrase to describe two pictures (e.g., "ball and hat") or produced the same phrases in response to pairs of written words. For the picture naming condition, control subjects showed an interference effect for semantically related pictures relative to unrelated pictures. This interference effect was greatly exaggerated for two patients with semantic short-term memory deficits but not for a patient with a phonological STM deficit. For the written words, control subjects showed a small facilitatory effect for the onset of phrases containing semantically related words. One of the patients with a semantic STM deficit who was tested on picture naming was also tested on these materials and showed a small facilitatory effect within the range of controls. The findings support the contention that speech planning is carried out at a phrasal level at the lexical-semantic level and that the capacities that support semantic retention in list recall support speech production planning.     

Biochemical characterization of new strains of<Emphasis Type="Italic"> Trypanosoma cruzi</Emphasis> and<Emphasis Type="Italic"> T. rangeli</Emphasis> isolates from Peru and Mexico

Seven trypanosome stocks isolated have been characterized by lectin agglutination, isoenzyme analysis, and the end products excreted. The stocks were isolated from different geographic areas—one from Mexico (TM5), and six from Peru, four of these isolated from different species of triatoma (TP504, TP702, TP704 and TP706), the other two isolated from the salivary glands of Rhodnius ecuadorensis (TRa605 and TRa606). Additionally, one strain of Trypanosoma cruzi isolated from a human case (strain TC-Maracay) and one strain of T. rangeli (TRa, Cajamarca-Peru strain), characterized and maintained in our laboratory, were used as reference strains. According to statistical study, the stocks were grouped into three clusters: (1) cluster I included the reference strain of T. cruzi (TC-Maracay); (2) cluster II was subdivided into two groups—subcluster IIA for the Mexican isolate (TM5) and subcluster IIB for the Peruvian ones, isolated from the salivary glands of Rhodnius ecuadorensis (TRa 605 and TRa 606) and the reference strain T. rangeli (TRa); these two new isolates were classified as T. rangeli; and (3) cluster III for the rest of the Peruvian isolates, which should be considered at least as a different strain from the T. cruzi strain Maracay. We show that the identification of T. cruzi and T. rangeli in mixed infections is readily achieved by biochemical methods. These findings identified three clusters of Mexican and Peruvian stocks that correlate with geographic origin, although assignment to a T. cruzi linage was not possible.     

Combination of PCR targeting the VD2 of omp1 and reverse line blot analysis for typing of urogenital Chlamydia trachomatis serovars in cervical scrape specimens

In this study we developed and evaluated a new PCR-based typing assay, directed to the VD2 region of the omp1 gene, for the detection and typing of urogenital Chlamydia trachomatis infections. A nested VD2 PCR-reverse line blot (RLB) assay was developed for the typing of nine different urogenital serovars of C. trachomatis. The assay developed was tested with reference strains of C. trachomatis serovars and cervical scrapes of 86 Colombian women previously found to be positive for C. trachomatis by using plasmid PCR. Two sets of primers directed to the VD2 region of the omp1 gene of C. trachomatis were designed, and fragments of 220 and 166 bp were generated in the primary and nested PCRs, respectively. In addition, an RLB assay was developed to identify nine different urogenital serovars of C. trachomatis (Ba, D, E, F, G, H, I, J, and K) and group controls, including group B (Ba, D, and E), group C (I, J, K, and H), and an intermediate group (F and G). Using this assay, we were able to type 81 of the 86 samples (94.2%). Of these samples, 91.3% were single C. trachomatis infections, and 8.7% were multiple infections. The most common serovars identified were serovars D (22.2%), F (18.5%), G (13.6%), and E (12.3%). Of the women with multiple C. trachomatis infections, >50% contained both serovars D and E. The nested VD2 PCR-RLB developed is a simple, fast, and specific method for the identification of individual urogenital C. trachomatis serovars previously detected by using plasmid PCR. Moreover, it is an appropriate method for studying multiple C. trachomatis infections and for use in large epidemiological studies.