Cardiopulmonary deconditioning and plasma volume loss are not sufficient to provoke orthostatic hypertension.

Orthostatic hypertension, defined by an increase of systolic blood pressure (SBP) of ≥20 mmHg upon standing, harbors an increased cardiovascular risk. We pooled data from two rigorously conducted head-down tilt bedrest studies to test the hypothesis that cardiopulmonary deconditioning and hypovolemia predispose to orthostatic hypertension. With bedrest, peak VO2 decreased by 6 ± 4 mlO2/min/kg (p < 0.0001) and plasma volume by 367 ± 348 ml (p < 0.0001). Supine SBP increased from 127 ± 9 mmHg before to 133 ± 10 mmHg after bedrest (p < 0.0001). In participants with stable hemodynamics following head-up tilt, the incidence of orthostatic hypertension was 2 out of 67 participants before bedrest and 2 out of 57 after bedrest. We conclude that in most healthy persons, cardiovascular deconditioning and volume loss associated with long-term bedrest are not sufficient to cause orthostatic hypertension.

Lower body negative pressure reduces jugular and portal vein volumes and counteracts the elevation of middle cerebral vein velocity during long-duration spaceflight.

Cephalad fluid shifts in space have been hypothesized to cause the spaceflight-associated neuro-ocular syndrome (SANS) by increasing the intracranial-ocular translaminal pressure gradient. Lower body negative pressure (LBNP) can be used to shift upper-body blood and other fluids toward the legs during spaceflight. We hypothesized that microgravity would increase jugular vein volume (JVvol), portal vein cross-sectional area (PV), and intracranial venous blood velocity (MCV) and that LBNP application would return these variables toward preflight levels. Data were collected from 14 subjects (11 males) before and during long-duration International Space Station (ISS) spaceflights. Ultrasound measures of JVvol, PV, and MCV were acquired while seated and supine before flight and early during spaceflight at day 45 (FD45) and late at day 150 (FD150) with and without LBNP. JVvol increased from preflight supine and seated postures (46 ± 48% and 646 ± 595% on FD45 and 43 ± 43% and 702 ± 631% on FD150, P < 0.05), MCV increased from preflight supine (44 ± 31% on FD45 and 115 ± 116% on FD150, P < 0.05), and PV increased from preflight supine and seated (51 ± 56% on FD45 and 100 ± 74% on FD150, P < 0.05). Inflight LBNP of -25 mmHg restored JVvol and MCV to preflight supine level and PV to preflight seated level. Elevated JVvol confirms the sustained neck-head blood engorgement inflight, whereas increased PV area supports the fluid shift at the splanchnic level. Also, MCV increased potentially due to reduced lumen diameter. LBNP, returning variables to preflight levels, may be an effective countermeasure.NEW & NOTEWORTHY Microgravity-induced fluid shifts markedly enlarge jugular and portal veins and increase cerebral vein velocity. These findings demonstrate a marked flow engorgement at neck and splanchnic levels and may suggest compression of the cerebral veins by the brain tissue in space. LBNP (-25 mmHg for 30 min) returns these changes to preflight levels and, thus, reduces the associated flow and tissue disturbances.

Seropositivity for Trypanosoma cruzi and Leishmania mexicana in dogs from a metropolitan region of Central Mexico.

Trypanosoma cruzi and Leishmania mexicana are parasites of humans and other mammals, causing American Trypanosomiasis and Cutaneous Leishmaniasis, respectively. Domestic dogs are considered key hosts for these parasites in the domicile and peridomicile cycles of transmission, due to their abundance and contact with human population. In Mexico, there are few studies that involve the study of infection with these parasites in dogs, and have only been carried out mainly in the endemic areas for these diseases. In the state of Querétaro (Mexico), infections with both parasites have been reported for dogs only from rural areas, with no records for the metropolitan zone. We analyzed the seropositivity to T. cruzi and L. mexicana in dogs from localities within of the metropolitan zone of Querétaro City in order to determine if these animals are exposed to these parasites and thus, could be an important part of the transmission cycle of these trypanosomatids in a densely populated urban region within the state of Querétaro, Mexico. Serum samples were collected from 303 dogs housed in the Animal Control centers of the municipalities of Querétaro and El Marques, analyzed by indirect ELISA and Western Blot using as an antigen the Iron Superoxide Dismutase (FeSODe) of the parasites. From the total serum samples, we detected 10.2% of seropositivity for T. cruzi and 2.9% for L. mexicana. Our results represent the first evidence of infection with T. cruzi in domestic dogs from the Metropolitan Zone of Querétaro, and the first record for L. mexicana in Central Mexico. Ongoing investigations seek to confirm the circulation of these parasites in the area to evaluate the risk associated to the human population.

The -675 4G/5G PAI-1 polymorphism confers genetic susceptibility to systemic lupus erythematosus, its clinical manifestations, and comorbidities in Mexican-Mestizo population.

Systemic lupus erythematosus (SLE) involves a broad range of factors that contribute to the development of the disease and its comorbidities. Genetic predisposition influences the development of SLE, and the -675 4G/5G PAI-1 polymorphism has been associated with several pathologies with a chronic inflammatory component. Our objective was to investigate the genetic association between the -675 4G/5G PAI-1 polymorphism with SLE, its clinical manifestations, and comorbidities in a Mexican-Mestizo population. The -675 PAI-1 polymorphism was determined by PCR-RFLP in 716 subjects: 293 SLE patients and 423 control subjects. Significant associations for SLE genetic susceptibility were found in carriers of 4G/5G (OR = 2.63; CI 1.81-3.87; p < .001) and 4G/4G (OR = 2.70; CI 1.62-4.51; p < .001) genotype in comparison with the 5G/5G genotype; 4G allele carriers also presented genetic risk for SLE (OR = 1.63; CI 1.31-2.03; p < .001) compared to the 5G allele. Following a dominant genetic model, a similar association was found with the 4G allele to SLE (OR = 2.66; CI1.84-3.84; p < .001). The 4G/5G genotype was associated with shorter disease duration (p = .039), as well as lower levels of haemoglobin (p = .001) and haematocrit (p = .009); the need for prednisone treatment (p = .001), higher BMI (p = .03), presence of type 2 DM (p = .015), clinical activity (Mex-SLEDAI = 57%; p = .047), Chronicity (SLICC-ACR = 0; p = .015) and CRP levels (p = .015) were associated with 5G/5G genotypes. In conclusion, the -675 4G/5G and 4G/4G PAI-1genotypes were found as genetic risk markers of susceptibility for SLE in the Mexican-Mestizo population, and each genotype could influence the clinical manifestations and comorbidities differently in SLE.

Simulating the Lunar Environment: Partial Weightbearing and High-LET Radiation-Induce Bone Loss and Increase Sclerostin-Positive Osteocytes.

Exploration missions to the Moon or Mars will expose astronauts to galactic cosmic radiation and low gravitational fields. Exposure to reduced weightbearing and radiation independently result in bone loss. However, no data exist regarding the skeletal consequences of combining low-dose, high-linear energy transfer (LET) radiation and partial weightbearing. We hypothesized that simulated galactic cosmic radiation would exacerbate bone loss in animals held at one-sixth body weight (G/6) without radiation exposure. Female BALB/cByJ four-month-old mice were randomly assigned to one of the following treatment groups: 1 gravity (1G) control; 1G with radiation; G/6 control; and G/6 with radiation. Mice were exposed to either silicon-28 or X-ray radiation. (28)Si radiation (300 MeV/nucleon) was administered at acute doses of 0 (sham), 0.17 and 0.5 Gy, or in three fractionated doses of 0.17 Gy each over seven days. X radiation (250 kV) was administered at acute doses of 0 (sham), 0.17, 0.5 and 1 Gy, or in three fractionated doses of 0.33 Gy each over 14 days. Bones were harvested 21 days after the first exposure. Acute 1 Gy X-ray irradiation during G/6, and acute or fractionated 0.5 Gy (28)Si irradiation during 1G resulted in significantly lower cancellous mass [percentage bone volume/total volume (%BV/TV), by microcomputed tomography]. In addition, G/6 significantly reduced %BV/TV compared to 1G controls. When acute X-ray irradiation was combined with G/6, distal femur %BV/TV was significantly lower compared to G/6 control. Fractionated X-ray irradiation during G/6 protected against radiation-induced losses in %BV/TV and trabecular number, while fractionated (28)Si irradiation during 1G exacerbated the effects compared to single-dose exposure. Impaired bone formation capacity, measured by percentage mineralizing surface, can partially explain the lower cortical bone thickness. Moreover, both partial weightbearing and (28)Si-ion exposure contribute to a higher proportion of sclerostin-positive osteocytes in cortical bone. Taken together, these data suggest that partial weightbearing and low-dose, high-LET radiation negatively impact maintenance of bone mass by lowering bone formation and increasing bone resorption. The impaired bone formation response is associated with sclerostin-induced suppression of Wnt signaling. Therefore, exposure to low-dose, high-LET radiation during long-duration spaceflight missions may reduce bone formation capacity, decrease cancellous bone mass and increase bone resorption. Future countermeasure strategies should aim to restore mechanical loads on bone to those experienced in one gravity. Moreover, low-doses of high-LET radiation during long-duration spaceflight should be limited or countermeasure strategies employed to mitigate bone loss.

Simulated resistance training, but not alendronate, increases cortical bone formation and suppresses sclerostin during disuse.

Mechanical loading modulates the osteocyte-derived protein sclerostin, a potent inhibitor of bone formation. We hypothesized that simulated resistance training (SRT), combined with alendronate (ALEN) treatment, during hindlimb unloading (HU) would most effectively mitigate disuse-induced decrements in cortical bone geometry and formation rate (BFR). Sixty male, Sprague-Dawley rats (6-mo-old) were randomly assigned to either cage control (CC), HU, HU plus either ALEN (HU+ALEN), or SRT (HU+SRT), or combined ALEN and SRT (HU+SRT/ALEN) for 28 days. Computed tomography scans on days -1 and 28 were taken at the middiaphyseal tibia. HU+SRT and HU+SRT/ALEN rats were subjected to muscle contractions once every 3 days during HU (4 sets of 5 repetitions; 1,000 ms isometric + 1,000 ms eccentric). The HU+ALEN and HU+SRT/ALEN rats received 10 µg/kg ALEN 3 times/wk. Compared with the CC animals, HU suppressed the normal slow growth-induced increases of cortical bone mineral content, cortical bone area, and polar cross-sectional moment of inertia; however, SRT during HU restored cortical bone growth. HU suppressed middiaphyseal tibia periosteal BFR by 56% vs. CC (P < 0.05). However, SRT during HU restored BFR at both periosteal (to 2.6-fold higher than CC) and endocortical (14-fold higher than CC) surfaces (P < 0.01). ALEN attenuated the SRT-induced BFR gains during HU. The proportion of sclerostin-positive osteocytes in cortical bone was significantly higher (+121% vs. CC) in the HU group; SRT during HU effectively suppressed the higher proportion of sclerostin-positive osteocytes. In conclusion, a minimum number of high-intensity muscle contractions, performed during disuse, restores cortical BFR and suppress unloading-induced increases in sclerostin-positive osteocytes.

Valoración de la repercusión del tabaco en la función pulmonar según el sexo / No disponible

Objetivo: Valorar la posible existencia de diferencias, en función del sexo, de la repercusión del tabaco sobre la función pulmonar. Pacientes y método: Se realizó un estudio descriptivo transversal (primer trimestre 2010), en tres ZBS de Toledo. Los participantes fueron fumadores mayores de 18 años (se excluyeron los pacientes con patología oncológica pulmonar, fibrosis quística, enfermedad pulmonar profesional, disfunciones cognitivas, contraindicaciones para poder realizar una espirometría, y no ser hispano- hablantes). Tras contactar telefónicamente, se citó a los pacientes para realizar una espirometría aprovechando dicha situación para realizar el consejo antitabaco. Si padecían un proceso respiratorio agudo se retrasó la cita diez días tras resolución del cuadro. Se recogió: edad, sexo, edad de inicio de hábito tabáquico, índice tabáquico (IT), función pulmonar- espirometría. Resultados: N= 153. Edad media 49±13,59 años. 61,4% hombres. Edad media inicio del consumo de tabaco 18,18±5,95 (inferior en hombres sin diferencias signifi cativas). Índice tabáquico: mediana 25 (RI 36-15), con diferencias signifi cativas entre sexos (hombres 28 vs mujeres 23; z=-2,107 p<0,05). Los valores medios de los datos espirométricos fueron: CVF: 86,41 (DE 17,44); FEV1: 88,94 (DE 18,09); FEV1/CVF: 85,01 (DE 13,64); MEF25-75: 87,94 (DE 32,42). Existían diferencias signifi cativas entre sexos en los valores medios de CVF, FEV1 y MEF25-75. Un 39,1% tenía un FEV1/CVF < 80 y el 16,99% valores de MEF25-75 <60, sin diferencias por sexos en estos grupos. En hombres, el IT se correlaciona signifi cativamente con CVF (rho: -0,309; p<0,001), FEV1 (rho: -0,320; p<0,001) y MEF25-75 (rho: -0,211; p<0,05), no encontrándose correlaciones significativas entre estos parámetros y el IT en mujeres. Se creó un modelo de regresión lineal entre IT y FEV1 para cada sexo obteniéndose una B= -0,035 en mujeres y una B=-0.182 en varones. Conclusiones: En nuestra muestra, la afectación que produce el tabaco parece ser diferente entre hombres y mujeres, con mayor repercusión en los hombres. Sería necesario realizar nuevos estudios para contrastar estos resultados (AU)

No disponible

Susceptibility of Campylobacter jejuni to organic acids and monoacylglycerols.

Organic acids can be used as feed supplements or for treatment of poultry carcasses in processing plants. The antimicrobial activity of nineteen organic acids and two monoacylglycerols in cultures of Campylobacter jejuni CCM 6214(T) (ATCC 33560) was determined using a SYBR Green-based real-time PCR assay. The IC(50) was a concentration at which only 50 % of a bacteria specific DNA sequence was amplified. Caprylic, capric and lauric acids were the most efficient antimicrobials among the compounds tested (IC(50) < or = 0.1 mg/mL). In a weakly acidic environment (pH 5.5), the antimicrobial activity was more pronounced than at pH 6.5. At pH 5.5, oleic and fumaric acid also had clear antimicrobial activity, as did monocaprylin. The antimicrobial activity of acetic, butyric, stearic and succinic acid was low. In cells treated with fumaric acid, the potential of potassium and tetraphenylphosphonium ion-selective electrodes changed, indicating an increase in cytoplasmic and outer membrane permeability, respectively. No changes in membrane permeability were observed in cells treated with capric acid or monocaprin. Transmission electron microscopy revealed separation of the inner and outer membrane in cells treated with capric and fumaric acid, as well as cytoplasmic disorganization in cells exposed to capric acid.

Palatal zygomycosis: experience of 21 cases.

OBJECTIVE: To present a clinical report of palatal zygomycosis, its epidemiological, mycological features, and our treatment experience. DESIGN: Retrospective report. SUBJECTS AND METHODS: This is a 25-year long retrospective trial of clinically and mycologically proven cases of zygomycosis. Some patients underwent a biopsy of the palatal lesion and autopsy. This study reports the treatment experience with amphotericin B alone and in combination with itraconazole and fluconazole. RESULTS: Twenty-one cases (18.75%) of zygomycosis with palatal involvement were included in the study, from a total of 112 cases screened. Mean age was 36.5 years, with 18 adults and three children. The associated pre-disposing factors were: ketoacidotic diabetes (five type-1 and 15 type-2), and acute leukaemia in one patient. The clinical varieties were as follows: 19 cases of rhinocerebral (RC) involvement and two disseminated cases. Palatal ulcers occurred in 3/21 early cases (14.3%) and in 16/21 cases after the nasal involvement. All patients received amphotericin B; in four patients, it was combined with itraconazole and four with fluconazole. Clinical and mycological cure was achieved in 4/21 patients (19.04%). CONCLUSION: Zygomycosis with palatal involvement occurs in around 18% of cases, usually associated with RC modalities; it has an acute and generally lethal course.

Heterogeneity of responses to orthostatic stress in homozygous twins.

Early analysis into the role of genetics on cardiovascular regulation has been accomplished by comparing blood pressure and heart rate in homozygous twins during unstressed, resting physiological conditions. However, many variables, including cognitive and environmental factors, contribute to the regulation of cardiovascular hemodynamics. Therefore, the purpose of this study was to determine the hemodynamic response of identical twins to an orthostatic stress, ranging from supine rest to presyncope. Heart rate, arterial blood pressure, middle cerebral artery blood velocity, an index of cerebrovascular resistance, cardiac output, total peripheral resistance, and end-tidal carbon dioxide were measured in 16 healthy monozygotic twin pairs. Five minutes of supine resting baseline data were collected, followed by 5 min of 60 degrees head-up tilt. After 5 min of head-up tilt, lower body negative pressure was applied in increments of 10 mmHg every 3 min until the onset of presyncope, at which time the subject was returned to the supine position for a 5-min recovery period. The data indicate that cardiovascular regulation under orthostatic stress demonstrates a significant degree of variance between identical twins, despite similar orthostatic tolerance. As the level of stress increases, so does the difference in the cardiovascular response within a twin pair. The elevated variance with increasing stress may be due to an increase in the role of environmental factors, as the influential role of genetics nears a functional limit. Therefore, although orthostatic tolerance times were very similar between identical twins, the mechanism involved in sustaining cardiovascular function during increasing stress was different.

Lower body negative pressure treadmill exercise is more comfortable and produces similar physiological responses as weighted vest exercise.

Lower body negative pressure (LBNP) treadmill exercise can generate a hypergravity load on the lower body that may improve athlete performance by mechanical and cardiovascular adaptations. This study compared the cardiovascular responses, subjective exertion and discomfort levels produced by LBNP exercise with those generated by a weighted vest (WV). We hypothesized that LBNP exercise is more comfortable than WV exercise at comparable levels of exercise. Nine subjects exercised on a treadmill at nine conditions, at 5.5 mph for 15 minutes, in which they ran in random order to avoid confounding effects: 100 %, 110 %, 120 %, 130 %, and 140 % body weight (BW), the latter four conditions were achieved by either LBNP chamber or WV. Heart rate (HR) and oxygen consumption (.VO(2)) were monitored continuously using ECG and open circuit spirometry. At the end of each test, subjects were asked to give discomfort and exertion scores using a ten-point visual analog scale (10 = maximal discomfort and exertion). For both HR and .VO(2), no significant differences were observed between LBNP and WV. Subjects reported significantly higher discomfort levels when exercising with the WV than with the LBNP at 120 % BW (5.1 +/- 0.55 vs. 3.1 +/- 0.64; p < 0.05), 130 % BW (6.2 +/- 0.42 vs. 2.3 +/- 0.44; p < 0.01) and 140 % BW (6.9 +/- 0.27 vs. 4.7 +/- 0.60; p < 0.01), while maintaining similar exertions at all conditions. Based on these results, LBNP exercise is more comfortable than standard WV exercise, while maintaining similar exertion, HR and .VO(2) values.

Cu(II) complexes with a sulfonamide derived from benzoguanamine. Oxidative cleavage of DNA in the presence of H2O2 and ascorbate.

Reaction between benzoguanamine (2,4-diamino-6-phenyl-1,3,5-triazine) and 2-mesitylenesulfonyl chloride leads to formation of a sulfonamide able to form two mononuclear Cu(II) complexes with a CuL(2) stoichiometry. The local environment of the metal cation is a distorted octahedron, with two ligands and two solvent molecules; both complexes crystallize in the monoclinic structure, space group P2(1), with Z=2. In the presence of ascorbate/H(2)O(2,) the two complexes significantly cleavage double-strand pUC18 DNA plasmid. Both complexes exhibit more nuclease efficiency that the copper phenantroline complex. From scavenging reactive oxygen studies we conclude that the hydroxyl radical and a singlet oxygen-like entity, such a peroxide copper complex, are the radical species involved in the DNA damage.

Oxidative cleavage of DNA by a new ferromagnetic linear trinuclear copper(II) complex in the presence of H2O2/sodium ascorbate.

A new trinuclear copper(II) complex has been synthesized and structurally characterized: [Cu(3)(L)(2)(HCOO)(2)(OH)(2)](infinity) (HL = (N-pyrid-2-ylmethyl)benzenesulfonylamide). In the complex, the central copper ion is six-coordinated. The coordination spheres of the terminal copper atoms are square pyramidal, the apical positions being occupied by a sulfonamido oxygen of the contiguous trimer. As a consequence, the complex can be considered a chain of trinuclear species. The three copper atoms are in a strict linear arrangement, and adjacent coppers are connected by a hydroxo bridge and a bidentate syn-syn carboxylato group. The mixed bridging by a hydroxide oxygen atom and a bidentate formato group leads to a noncoplanarity of the adjacent basal coordination planes with a dihedral angle of 61.4(2) degrees. Susceptibility measurements (2-300 K) reveal a strong ferromagnetic coupling, J = 79 cm(-1), leading to a quartet ground state that is confirmed by the EPR spectrum. The ferromagnetic coupling arises from the countercomplementarity of the hydroxo and formato bridges. The trinuclear complex cleaves DNA efficiently, in the presence of hydrogen peroxide/sodium ascorbate. tert-Butyl alcohol and sodium azide inhibit the oxidative cleavage, suggesting that the hydroxyl radical and singlet oxygen are involved in the DNA degradation.

Nuclease activity of [Cu(sulfathiazolato)(2)(benzimidazole)(2)]2MeOH. Synthesis, properties and crystal structure.

The [Cu(sulfathiazolato)(2)(benzimidazole)(2)]2MeOH complex has been synthesised and characterised. It crystallises in the monoclinic system, space group C1c1, with unit cell dimensions a=18.829(7) A, b=12.206(3) A, c=17.233(5) A, alpha=90.06(2) degrees, beta=97.28(3) degrees, gamma=90.21(3) degrees and Z=4. The geometry around the copper(II) ion is intermediate between tetrahedral and square planar. The complex produces cleavage of plasmid pUC18 in presence of reducing agents. The efficiency of cleavage reaction of the title compound with pUC18 and with different reducing agents follows the order ascorbate-H(2)O(2)>ascorbate>MPA>dithiothreitol>H(2)O(2).

Complexes of Ni(II) and Cu(II) with ofloxacin. Crystal structure of a new Cu(II) ofloxacin complex.

Several coordination compounds formed between Ni(II) or Cu(II) with ofloxacin have been synthesised and characterised. According to elemental chemical analysis and FT-IR spectroscopy data, direct reaction of Ni(II) and Cu(II) salts with ofloxacin leads to formation of precipitates for which mass spectrometry demonstrates their polymeric nature. However, crystalline [Cu(oflo)2(H2O)].2H2O is formed if the reaction is carried out in the presence of ammonia. This complex crystallises in the triclinic system, space group P-1 with a=9.2887(12), b=11.2376(14), c=17.874(2) A, alpha=92.12(3), beta=95.39(3), gamma=91.71(3) degrees and Z=2. The local geometry around the Cu(II) ion is a slightly distorted square base pyramid. Electronic spectra, magnetic susceptibility measurements and EPR spectra of the synthesised complexes indicate a tetragonal environment.

[Vaccination against hepatitis B at the Palma-Palmilla Health Center of Málaga]. / Vacunación contra la hepatitis B en el Centro de Salud Palma-Palmilla de Málaga.

AIM: To describe the results of a programme of anti-hepatitis B vaccination of high-risk groups. DESIGN: Observational descriptive study, of a retrospective character. SITE. At a community level within the confines of Primary Care in the Palma-Palmilla (Málaga) Health Centre, between June 1989 and March 1990. PATIENTS AND OTHER PARTICIPANTS: Individuals with a high risk of Hepatitis B infection, according to a modified CDC (Centre for Diseases Control) scale. The subjects were found during their attendance as patients and from among the Health Centre staff. INTERVENTIONS: The second generation vaccine developed by genetic engineering (Engerix B) was used. It was administered by intramuscular injection in a dosage of 20 mcg to those weighing more than 25 kilos; and of 10 mcg to those weighing less than 25 kilos. The vaccination pattern was of three doses in months 0, 1 and 6, followed by a monthly sero-conversion check. MEASUREMENTS AND MAIN FINDINGS: 169 individuals began the vaccination programme: 17.7% were health workers and 81.6% lived with carriers of the virus. 87.6% completed the vaccination programme. Sero-conversion in the individuals controlled was 95.5%. Only five patients were sero-negative after the third vaccination. Of these four cases achieved sero-conversion after a fourth or fifth dosage. CONCLUSIONS: We found there was a high rate of sero-conversion; and also high acceptance of the programme by those living with a carrier.