Analgesic, antiinflammatory and central depressor effects of the hydroalcoholic extract and fractions from Aeolanthus suaveolens

This work studied antinociceptive, antiedematogenic and central depressor effects of the hydroalcoholic extract (HAE) from Aeolanthus suaveolens and its fractions: hexane (ASHAE-H), ethyl acetate (ASHAE-A), aqueous (ASHAE-E) and precipitate (ASHAE-PPT) in experimental models in mice. The highest activity in the writhing test was presented by ASHAE-A followed by ASHAE-PPT and ASHAE-E and the lowest by ASHAE-H. In the formalin test the effect was manifested at both phases, although more intensely at the 2nd phase of the response. In this test, the most active fraction was ASHAE-PPT causing inhibitions of the order of 76 and 90% of the 2nd phase of the test at the doses of 10 and 100 mg/kg i.p., respectively. Naloxone reversed the effects of ASHAE-PPT in both phases of the test, suggesting the participation of the opioid system in the antinociceptive effect. On the other hand, the HAE effect on both phases of the formalin test was only partially reversed by naloxone, suggesting that the extract presents more than one active compound, and at least one, of a polar nature, acting through the opioid system. HAE and ASHAE-PPT presented antiinflammatory activity and were very effective in decreasing the mouse paw edema induced by carrageenan. All fractions significantly decreased locomotor activity in the open field test in mice. However, only the nonpolar fractions presented myorelaxant activity as demonstrated by the rota rod test.     

High tumor incidence and activation of the PI3K/AKT pathway in transgenic mice define AIB1 as an oncogene

The gene encoding AIB1, an estrogen receptor coactivator, is amplified in a subset of human breast cancers. Here we show that overexpression of AIB1 in transgenic mice (AIB1-tg) leads to mammary hypertrophy, hyperplasia, abnormal postweaning involution, and the development of malignant mammary tumors. Tumors are also increased in other organs, including the pituitary and uterus. AIB1 overexpression increases mammary IGF-I mRNA and serum IGF-I protein levels. In addition, IGF-I receptor and downstream signaling molecules are activated in primary mammary epithelial cells and mammary tumor cells derived from AIB1-tg mice. Knockdown of AIB1 expression in cultured AIB1-tg mammary tumor cells leads to reduced IGF-I mRNA levels and increased apoptosis, suggesting that an autocrine IGF-I loop underlies the mechanism of AIB1-induced oncogenesis.     

CagA antibodies as a marker of virulence in chilean patients with Helicobacter pylori infection

BACKGROUND: The bacterial and host factors that influence the clinical outcomes of the Helicobacter pylori infection have not been fully identified. Cytotoxin-associated gene product (CagA), one of the virulence factors, has been associated with a more aggressive form of infection. The authors studied the relationship between CagA status and clinical outcome in Chilean children and adults with H. pylori infection. METHODS: One hundred eighty consecutive patients undergoing upper gastrointestinal endoscopic analysis were enrolled after informed consent was obtained. Rapid urease test and histologic analysis were used to detect H. pylori infection. IgA and IgG antibodies to H. pylori whole cell antigen preparation and IgG antibodies to CagA were measured by enzyme-linked immunosorbent assay (ELISA). RESULTS: H. pylori infection was detected in 42% of the patients by biopsy or urease test and in 38% and 20% of patients by IgG and IgA antibodies, respectively. The prevalence of H. pylori either by the invasive or the serologic tests was directly related to patient age. Among patients with H. pylori, there was no significant association between age and prevalence of CagA. Nearly 70% of the patients with H. pylori and peptic ulcer disease had CagA-positive strains. In contrast, only 49% of the patients with chronic gastritis alone had CagA-positive strains (P < 0.05). CONCLUSIONS: In Chile, patients infected with H. pylori have a proportion of CagA-positive strains similar to that reported in developed countries. CagA prevalence was not significantly different in adults and children infected with H. pylori, suggesting that variations in clinical outcome may be related to host immune or environmental factors.     

Co-treatment with melanotan-II,a potent melanocortin,does not protect against cisplatin ototoxicity

Cisplatin, an important chemotherapeutic agent, has severe dose-limiting side effects including peripheral neurotoxicity and ototoxicity. Peripheral neurotoxicity can be delayed or prevented by simultaneous treatment with a class of neuropeptides known as melanocortins. Examples are ORG 2766, alpha-melanocyte stimulating hormone (alpha-MSH) and melanotan-II (MT-II). In albino guinea pigs, our group has found that ORG 2766 and alpha-MSH can also reduce cisplatin-induced ototoxicity. In this study we investigated the possibly protective effects of MT-II upon cisplatin ototoxicity. Guinea pigs, equipped with a permanent round-window electrode for electrocochleography, were treated with cisplatin (1.5 mg/kg/day intraperitoneal) and simultaneously with MT-II (30 or 3 microg/kg/day subcutaneous) or saline until a 40 dB suppression of the compound action potential (CAP) threshold (3 microV criterion) at 8 kHz occurred. This -40 dB criterion was reached after 5-18 days. Thereafter, the treatment was stopped, but electrocochleography was continued for another 4 weeks. The number of days in which the -40 dB criterion was reached in the MT-II co-treated group did not differ from the period in the saline group. Ten days after the end of the treatment a spontaneous recovery of the CAP was observed in all groups and at all frequencies, although it was more pronounced at lower frequencies. Also with respect to recovery, no differences were found between the saline and the MT-II co-treated group. Thus, in contrast with the otoprotective properties of other melanocortins, MT-II has no protective properties against cisplatin-induced ototoxicity, at least not with the doses applied here.     

Healing process induced by three composite prostheses in the repair of abdominal wall defects

The present study compared the performance of three composite prostheses used to repair abdominal wall defects in rabbits. Two of them [Parietex Compositereg (PC) and Composixreg (CS)] are commonly used in clinical practice and one was designed by the present team (PL-PU99). At 14 and 90 days postimplant, specimens were obtained for morphological, macrophage response (RAM-11) and morphometric and biomechanical analysis. The prosthetic area covered by adhesions was significantly greater (p < 0.05) in the CS group (6.83 plus minus 2.31 cm(2)) than in PC (0.11 +/- 0.02 cm(2)) or PL-PU99 (0.10 +/- 0.07 cm(2)). At 14 days, it was observed a homogeneous, organized, well-vascularized neoperitoneum that was significantly thicker (p < 0.05) in PL-PU99. Except in the CS implants, this layer was covered by a continuous mesothelium. All three composites achieved good recipient tissue integration. Highest macrophage levels were recorded at 14 days with significantly higher values in the PL-PU99 prosthesis. Biomechanical strength was significantly greater (p < 0.05) in CS at two weeks postimplant, but it was similar at 90 days. These findings suggest that the three composites show ideal integration with host tissue, along with similar biomechanical strength at 90 days, and significantly higher adhesion formation is induced by the CS prosthesis, possibly due to incomplete mesothelialization of the lower prosthetic surface.     

Human T-cell leukemia virus type I infection in various recipients of transplants from the same donor

BACKGROUND: The human T-cell lymphotrophic virus (HTLV) causes adult T-cell leukemia-lymphoma, tropical spastic paraparesis-HTLV type I, and associated myelopathy. METHODS: An analysis was performed of serum samples from a multiorgan donor and the five recipients. Also studied was the donor's family and the partner of one of the renal recipients. Serologic detection of anti-HTLV antibodies was carried out by enzyme immunoassay and Western blot to confirm and discriminate between HTLV types. Analysis of proviral DNA was performed by polymerase chain reaction and sequenced in the long terminal repeat region and the env gene. Peripheral blood mononuclear cell samples from all the recipients of the HTLV-I-positive organs and the donor's mother were studied. RESULTS: Two years after transplantation, three organ recipients positive for antibodies to HTLV-I were detected (two kidney transplants and one liver). All the recipients' serum samples were negative at the time of transplantation except those from the multiorgan donor. The donor's mother was born in Venezuela and was confirmed positive for antibodies to HTLV-I. The remaining family members were negative. HTLV-I DNA sequences were recovered, amplified, and sequenced from all the samples from the HTLV-I-positive recipients and the donor's mother. The homology of HTLV-I sequences was 100% in all cases. CONCLUSIONS: The authors are reporting the first documented case of HTLV-I infection in several transplant recipients sharing the same donor. The donor was infected by vertical transmission. HTLV-I infection has devastating consequences for some immunocompromised organ recipients. This emphasizes the need for a systematic survey of HTLV antibodies in all potential donors.     

Effect of the V1a/V2-AVP receptor antagonist,Conivaptan, on renal water metabolism and systemic hemodynamics in rats with cirrhosis and ascites

BACKGROUND: Selective V(2)-AVP receptor antagonists are effective in inducing aquaresis in humans and rats with cirrhosis, hyponatremia and water retention. However, it is unknown whether dual V(1a)/V(2)-AVP antagonists are also efficacious as aquaretic agents under these conditions. This is important, particularly considering that blockade of V(1a)-AVP receptors could aggravate cardiocirculatory function in decompensated cirrhosis.AIMS: To evaluate the renal, hormonal and hemodynamic effects induced by the chronic oral administration of the V(1a)/V(2)-AVP antagonist, Conivaptan, in rats with CCl(4)-induced cirrhosis, ascites and severe water retention.METHODS: We assessed the aquaretic efficacy of 10-day chronic oral administration of Conivaptan (0.5mg/kg body weight (bw)) in cirrhotic rats with hyponatremia and water retention. Urine volume (UV), osmolality (UOsm), and sodium excretion (U(Na)V) were measured daily. At the end of the study arterial pressure was also measured.RESULTS: Conivaptan produced an acute increase in UV, a reduction in UOsm and, at the end of the investigation, cirrhotic rats receiving the V(1a)/V(2)-AVP receptor antagonist did not show hyponatremia or hypoosmolality. Conivaptan also normalized U(Na)V without affecting creatinine clearance and arterial pressure.CONCLUSIONS: Dual V(1a)/V(2)-receptor antagonists may be therapeutically useful for the treatment of water retention and dilutional hyponatremia in human cirrhosis.