Walking modality affects respiratory muscle action and contribution to respiratory effort

We hypothesized that walking at increased speed or increasing gradient might have different effects on chest wall kinematics and respiratory muscle power components, and contribute differently to respiratory effort sensation. We measured the volumes of chest wall compartments by optoelectronic plethysmography, esophageal, gastric and transdiaphragmatic (P _di) pressures, and the sensation of the respiratory effort by a Borg scale in five normal subjects walking both at ascending gradient with constant speed (AG) and at ascending speed with constant gradient (AS). Chest wall kinematics, evaluated by displacement of chest wall compartments, did not show any significant difference between AS and AG. Muscle power, calculated as the product of mean flow and mean pressure, increased similarly, but its partitioning into pressure and velocity of shortening differed in the two modes. A greater increase in the pressure developed by the abdominal muscles (P _abm) (4.06-fold), and in the velocity of shortening of both rib cage inspiratory muscles (v _rcm,i) (2.01-fold) and the diaphragm (v _di) (1.90-fold) was associated with a lower increase in the pressure developed by the rib cage inspiratory muscles (P _rcm,i) (1.24-fold) and P _di (0.99-fold) with AG. Instead, with AS, a lower increase in P _abm (2.12-fold), v _rcm,i (1.66-fold) and v _di (1.54-fold) was associated with a greater increase in P _rcm,i (1.56-fold) and P _di (1.97-fold). A combination of P _abm and v _di during AG (Wald ²=23.19, P<0.0000), with the addition of P _rcm,i during AS (Wald ²=29.46, P<0.0000), was the best predictor of Borg score. In conclusion, the general strategy adopted by respiratory centers during different walking modes does not differ in terms of ventilation, chest wall kinematics, and respiratory muscle power production, whereas it does in terms of partitioning of power into pressure and velocity of shortening, and respiratory muscle contribution to respiratory effort sensation. Combinations of different patterns of flow and pressure generation made the respiratory effort sensation similar during AS and AG modes.     

Different levels of natural antibodies in chickens divergently selected for specific antibody responses

We studied the presence of Natural antibodies in plasma samples from individual birds from selected chicken lines at young and old age. Binding, specificity, and relative affinity to various antigens were determined in plasma from non-immunized female chickens at 5 weeks of age, and in plasma obtained from the same chickens one year later using indirect two-step ELISA. Birds were from three different lines. The lines were divergently selected for either high (H line) or low (L line) antibody titers to Sheep Red Blood Cells at 5 weeks of age, next to a random bred control (C line). Binding of plasma immunoglobulins (Ig) from all three lines was found with chicken-egg-white protein (CEP), ovalbumin (OVA), myoglobin (MYO), thyroglobulin (THYRO), keyhole limpet hemocyanin (KLH), bovine serum albumin (BSA), and transferrin (TRANS). Significantly higher binding to most antigens was found with plasma Ig from adult birds from the H line as compared to plasma Ig from the L line, whereas binding of plasma Ig from C-line birds was in between or similar to the H or L line, respectively. Binding of Ig to all antigens in all three lines was significantly higher in plasma obtained at one year of age as compared to plasma obtained at 5 weeks of age. A competitive ELISA with homologous and heterologous antigens was used for determining specificity of the antigen-binding antibodies. Nai;ve plasma samples were characterized by a broad binding to all antigens tested. Inhibition of binding to specific antigens was possible with a broad range of heterologous antigens, but highest competition of binding was obtained with homologous antigen. Both linear regression analysis of serial dilutions of the plasma Ig binding the antigens, as well as competitive ELISA with homologous antigen indicated that plasma Ig from the H line and plasma Ig from the L line had similar affinity characteristics to the antigens tested with the exception of OVA and KLH. Pooled non-immune plasma from H line birds bound to CEP, OVA, THYRO, TRANS, MYO, KLH, and salt-precipitated extracts and supernatants of extracts from chicken heart, spleen, liver, brain, bursa, thymus, and kidney, respectively, as determined by Western blotting. The increasing presence of antibodies in nai;ve chicken plasma binding heterologous and homologous (tissue) antigens indicates the presence of Natural antibodies in poultry. Apart from age, increasing levels of Natural antibodies may be related with the genetically based magnitude of specific antibody levels in the chicken lines studied.     

Stem cell therapy for neurodegenerative diseases: the issue of transdifferentiation

In the past few years research on stem cells has exploded as a tool to develop potential therapies to treat incurable neurodegenerative diseases. Stem cell transplantation has been effective in several animal models, but the underlying restorative mechanisms are still unknown. Several events such as cell fusion, neurotrophic factor release, endogenous stem cell proliferation, and transdifferentiation (adult cell acquisition of new unexpected identities) may explain therapeutic success, in addition to replacement of lost cells. This issue needs to be clarified further to maximize the potential for effective therapies. Preliminary stem transplantation trials have already been performed for some neurodegenerative diseases. There is no effective pharmacological treatment for amyotrophic lateral sclerosis, but recent preliminary data both in experimental and clinical settings have targeted it as an ideal candidate disease for the development of stem cell therapy in humans. This review summarizes recent advances gained in stem cell research applied to neurodegenerative diseases with a special emphasis to the criticisms put forward.     

Specific ultrarush desensitization in Hymenoptera venom-allergic patients.

BACKGROUND: Hymenoptera venom hypersensitivity is an epidemiologically important problem. The only effective treatment in the management of venom-allergic patients with a history of generalized reactions to insect sting is specific immunotherapy. OBJECTIVE: To demonstrate safety and effectiveness of a modified ultrarush desensitization protocol in venom-allergic patients. METHODS: Fifty-seven patients with Hymenoptera venom allergy underwent a specific 1-day ultrarush desensitization by the subcutaneous route, reaching the cumulative dose of 101.1 microg in 2.5 hours. The maintenance dose (100 microg) was administered after 15 days and thereafter once a month. Patients were followed up for a year. Antihistamines were withheld for 15 days before and during desensitization to not underestimate the incidence of adverse effects. RESULTS: All patients but I completed the ultrarush desensitization. (This patient discontinued the treatment because of a hypertensive crisis not related to the desensitization.) The treatment caused a rapid variation of immunological parameters (IgE, IgG4) since the 15th day. After the desensitization, skin prick test results became negative in 15 patients (27%, decrease of 3.5 log), whereas they decreased in 14 patients (25%, decrease of 1 log). Sixty-four percent showed no adverse effects. Only 7% had a mild systemic reaction. CONCLUSIONS: Ultrarush desensitization is an effective and safe therapy in the management of patients with Hymenoptera venom allergy. In fact, it provides a faster tolerance, without significant differences regarding incidence of severe adverse effects, compared with traditional and rush protocols. It can be adopted for all patients, even children and teenagers.     

Drug resistance mutations and newly recognized treatment-related substitutions in the HIV-1 protease gene: prevalence and associations with drug exposure and real or virtual phenotypic resistance to protease inhibitors in two clinical cohorts of antiretroviral experienced patients

This study aimed at identifying HIV-1 protease amino acid changes associated with protease inhibitor (PI) exposure and susceptibility. New amino acid substitutions were correlated with the number of experienced PIs, reaching statistical significance only for those at positions 3, 44, and 74. The correspondence multivariate model demonstrated that > or =3 experienced PIs and substitutions or mutations at positions 3, 46, 54, 73, 74, and 84 were correlated with PI cross-resistance, including resistance for lopinavir and amprenavir in this cohort of patients who were naive for these drugs.     

Trypanosoma cruzi is lysed by coelomic cytolytic factor-1, an invertebrate analogue of tumor necrosis factor, and induces phenoloxidase activity in the coelomic fluid of Eisenia foetida foetida.

A cytolytic protein named Coelomic Cytolytic Factor-1 (CCF-1) was isolated from the coelomic fluid of the earthworm Eisenia foetida foetida. Despite the absence of any gene homology, CCF-1 showed functional analogy with the mammalian cytokine tumour necrosis factor (TNF), particularly based on similar lectin-like activity. Indeed, both CCF-1 and TNF recognise N,N'-diacetylchitobiose and exert lytic activity on African Trypanosoma brucei brucei. In this report, we show that South-American Trypanosoma cruzi trypomastigotes, but not epimastigotes, were lysed by earthworm coelomic fluid or purified CCF-1. However, T. cruzi was less susceptible to lysis than T. brucei brucei. This lytic effect of coelomic fluid and CCF-1 on T. cruzi trypomastigotes was partially inhibited in the presence of anti-CCF-1 monoclonal antibody, antibody neutralising the lectin-like activity of TNF or N,N'-diacetylchitobiose. In contrast, this lytic effect was completely inhibited when using T. b. brucei. In addition, T. cruzi components, upon recognition by CCF-1 in E. f. foetida coelomic fluid, triggered the prophenoloxidase cascade, an invertebrate defence mechanism. These results further extend the functional analogies of CCF-1 and TNF, suggesting that both molecules share a similar lectin-like activity that has been conserved as an innate recognition mechanism in invertebrates and vertebrates. They also establish a link between stercorarian (T. cruzi) and salivarian (T. brucei) trypanosomatids having divergent phylogenetic origins and patterns of evolution, but possessing closely related cell surface sugar moieties.     

Ultrastructural analysis of pancreatic acinar cells from mice fed on genetically modified soybean

No direct evidence that genetically modified (GM) food may represent a possible danger for health has been reported so far; however, the scientific literature in this field is quite poor. Therefore, we investigated the possible effects of a diet containing GM soybean on mouse exocrine pancreas by means of ultrastructural, morphometrical and immunocytochemical analyses. Our observations demonstrate that, although no structural modification occurs in pancreatic acinar cells of mice fed on GM soybean, quantitative changes of some cellular constituents take place in comparison to control animals. In particular, a diet containing significant amount of GM food seems to influence the zymogen synthesis and processing.