Weak coordination between leaf structure and function among closely related tomato species.

Theory predicts that natural selection should favor coordination between leaf physiology, biochemistry and anatomical structure along a functional trait spectrum from fast, resource-acquisitive syndromes to slow, resource-conservative syndromes. However, the coordination hypothesis has rarely been tested at a phylogenetic scale most relevant for understanding rapid adaptation in the recent past or for the prediction of evolutionary trajectories in response to climate change. We used a common garden to examine genetically based coordination between leaf traits across 19 wild and cultivated tomato taxa. We found weak integration between leaf structure (e.g. leaf mass per area) and physiological function (photosynthetic rate, biochemical capacity and CO2 diffusion), even though all were arrayed in the predicted direction along a 'fast-slow' spectrum. This suggests considerable scope for unique trait combinations to evolve in response to new environments or in crop breeding. In particular, we found that partially independent variation in stomatal and mesophyll conductance may allow a plant to improve water-use efficiency without necessarily sacrificing maximum photosynthetic rates. Our study does not imply that functional trait spectra, such as the leaf economics spectrum, are unimportant, but that many important axes of variation within a taxonomic group may be unique and not generalizable to other taxa.

Upper gastrointestinal tract transit times of tablet and drinkable solution formulations of alendronate: a bioequivalence and a quantitative, randomized study using video deglutition.

The bioequivalence and upper digestive tract transit time of a drinkable solution of 70 mg/100 mL alendronate was compared to reference tablets. A randomized, single- dose, two-way crossover study of the rate of urinary recovery of alendronate during 36 h (AE((0-36 h))) by HPLC, in 104 healthy young male volunteers, showed that AE((0-36 h)) and the maximum excretion rate (R (max)) were within the accepted range of bioequivalence 81.8-105.7 and 81.7-106.2, respectively. To characterize the oesophageal passage time of the two alendronate formulations, we performed a randomized, controlled study, in 24 healthy men and women (mean 52 years old), who took the formulations standing or lying down, by an X-ray video deglutition system. When taken in the standing position, both formulations had equal mean transit times from mouth to stomach and tablet disintegration but data dispersion was significantly smaller with the liquid form. When taken in lying position, drinkable alendronate had shorter and less variable median transit times compared to the tablets. These results show that the drinkable alendronate formulation is bioequivalent to the tablets and may be advantageous in patients in whom the transit or disintegration of the tablets is impaired.

[Biomedicine philately]. / La filatelia biomedica.

Biomedicine is a vast field in philately or stamp collecting. It opens the topic the image of the goddess Hygeia, issued in a stamp from Nevis Island dated 1861. The first physicians to appear printed in stamps, in 1869, were three American constitutionalists, but only in 1937 there appear Dutch physicians as an acknowledgement of their contribution to public health. In Argentina the first stamp officially related to the topic was issued in 1944, to raise funds for the victims of the San Juan earthquake. Florentino Ameghino was the first scientist included in 1954, and in 1967 a stamp was issued in honour of Dr. Cecilia Grierson. Afterwards, Argentinean philately has recognized several of our scientists and physicians, congresses, universities, health campaigns, dentistry topics, chemistry, and nursery, among others, promoting a large amount of philatelic material in acknowledgement of the social value that Argentinean biomedical science has gained locally and abroad. Probably, it is a scientist, Dr. Bernardo Houssay, the Argentinean who has more often appeared in international philately.

Reducing Allostatic Load in Depression and Anxiety Disorders: Physical Activity and Yoga Practice as Add-On Therapies.

The allostatic load (AL) index constitutes a useful tool to objectively assess the biological aspects of chronic stress in clinical practice. AL index has been positively correlated with cumulative chronic stress (physical and psychosocial stressors) and with a high risk to develop pathological conditions (e.g., metabolic syndrome, cardiovascular pathology, inflammatory disorders) and the so-called stress-related psychiatric disorders, including anxiety and depressive disorders. Chronic stress has negative effects on brain neuroplasticity, especially on hippocampal neurogenesis and these effects may be reversed by antidepressant treatments. Several evidences indicate that non-pharmacological interventions based on physical activity and yoga practice may add synergizing benefits to classical treatments (antidepressant and benzodiazepines) for depression and anxiety, reducing the negative effects of chronic stress. The aim of this review is to provide a general overview of current knowledge on AL and chronic stress in relation to depression and anxiety, physical activity and yoga practice.

Assessment of material, structural, and functional properties of the human skeleton by pQCT systems.

Peripheral quantitative computed tomography (pQCT) systems measure bone parameters noninvasively using low radiation doses. This limits image resolution but is practical for the diagnosis and quantitative monitoring of the properties of the peripheral human skeleton. pQCT determines volumetric bone mineral density separately in trabecular and cortical bone. It may combine densitometry determinations with geometric estimates and use strain-stress indexes, and it may be used to analyze muscle variables in some areas, allowing the study of regional fragility. Experimental and clinical ex vivo studies show that pQCT variables correlate with biomechanical predictors of fragility and/or fractures. Since pQCT was approved by the US Food and Drug Administration in 1997, new skeletal regions (human femur and mandible) have been considered in the development of the system. Basically, pQCT explores intraindividual and interindividual variations in greater detail and compares the impact of skeletal diseases, risk factors, and anabolic and catabolic treatments within a given bone cross section.

25-Hydroxyvitamin D serum levels in rheumatic female patients in southeast Spain: The paradigm of daily optimal sunshine levels and inadequate vitamin D status.

BACKGROUND: Almeria is a region in southeast Spain with optimal sunlight levels, along with low pluvial and pollution rates. If exposure to sunlight is sufficient to maintain adequate levels of vitamin D (25OHD), this population should display high serum levels. OBJECTIVES: To describe 25OHD serum status in women from Almeria and evaluate the impact of long sunlight exposure along the seasons on 25OHD. METHODS: Cross-sectional study, performed in women consecutively recruited from an outpatient rheumatology clinic. Serum levels of 25OHD were assessed in all patients and evaluated according to age (<48 yrs, 48-53 yrs, 54-60 yrs and >60 yrs), season, and presence or absence of menopause. Clinical and laboratory variables that could affect status of vitamin D were also considered. RESULTS: The sample included 319 Caucasian female patients. Mean 25OHD were 30.2ng/ml with 195 (61.1%) exhibiting 25OHD inadequate serum levels. Season had a significant effect on 25OHD levels, with autumn being the season in which 25OHD serum levels remained well above 30ng/ml in all age bands, and winter the season with more levels of insufficiency. Menopause did not modify 25OH serum levels. Women whose age was below 48 and over 60 had inadequate levels of 25OHD during summer. CONCLUSIONS: Optimal levels of sunlight could not overcome the problem of inadequate 25OHD serum levels, particularly in elderly and young female population. Vitamin D supplementation may be recommended predominantly in winter and summer in this population.

Skeletal effects of long-term estrogen and testosterone replacement treatment in a man with congenital aromatase deficiency: evidences of a priming effect of estrogen for sex steroids action on bone.

The relative contribution of each sex steroid (i.e. estrogen and androgen) on bone in men and the relationships among sex steroids and changes in BMD and bone strength are still unknown. A defective BMD of bone tissue is constantly present in men with aromatase deficiency. This study evaluates the effects of different regimens of treatment with sex steroids over 7.3 years follow-up on BMD in an adult man affected by aromatase deficiency and by a concomitant mild hypogonadism, as previously described. The aim of the study is to provide additional data on the relative roles of androgens and estrogens in male bone metabolism. The effects of testosterone (T) treatment alone and estrogen (tE(2)) treatment alone as well as the effects of the combined treatment with testosterone and estradiol (T plus tE(2)) on areal BMD (aBMD) at dual-energy X-ray absorptiometry (DXA) and the effects of T plus tE(2) on volumetric BMD (vBMD), particular at cortical site, measured by peripheral quantitative computed tomography (pQCT), are investigated. Hormones and markers of bone turnover were monitored during all phases of the study. Treatment with tE(2) normalized serum estradiol, but only the combined treatment with T plus tE(2) normalized both serum estradiol and testosterone. Markers of bone turnover reached a pattern close to normality during T plus tE(2). The aBMD was little modified by T, but increased more during tE(2). T plus tE(2) resulted in a further increase in both aBMD at DXA and vBMD at pQCT. Cortical thickness increased during T plus tE(2) both in radius and tibia. Only the combined treatment led to optimal parameters of aBMD suggesting that testosterone needs estrogens as a permissive factor for a direct androgen anabolic action on bone in men.

Tolerability of intravenous pamidronate for the treatment of osteoporosis and other metabolic osteopathies: A retrospective analysis.

BACKGROUND: Intravenous disodium pamidronate has been described in the treatment of several osteopathies. Although tolerability has been found to be good in clinical trials, some mild to serious adverse events (AEs) have been reported. OBJECTIVES: The aims of this study were to analyze the toelrability of IV pamidronate in patients being treated for osteoporosis and other metabolic osteopathies and to describe particular patients with relative contraindications, because such cases are not commonly seen in daily clinical practice. METHODS: We performed a retrospective analysis of patients with different osteopathies who were administered IV infusions of pamidronate at doses ranging from 15 to 90 mg/infusion and 15 to 900 mg/year. The study was conducted in patients who had received treatment at the Institute of Metabolic Investigations, University of Salvador, Buenos Aires, Argentina, between January 1995 and December 2003. To rule out dose-related AEs, a comparison was made between patients who received fewer IV infusions and had cumulative doses of 120 to 180 mg/y (less frequent administration [LFA] group) and those patients who received regular infusions and had cumulative doses of >180 mg/year (frequent administration [FA] group). To confirm data obtained from medical records and to assess the occurrence of AEs, attempts were made to interview all patients by phone. The following information was verified for each patient included in the study: the reason for treatment, documented evidence of current diagnostic criteria, and whether the dose administered was adequate to treat the patient's condition. RESULTS: Six hundred eight patients (464 [76.3%]women, 144 [23.7%]men; mean [SD] age, 69 [10] years) with various osteopathies (osteoporosis, 367 [60.4%] of the patients; Paget's disease, 172 [28.3%]; Sudeck's disease, 63 [10.4%]; multiple myeloma, 3 [0.5%]; and bone metastases, 3 [0.5%]) were administered a total of 2933 IV infusions of pamidronate during the study period. We were able to confirm the clinical records of 69.4% (422/608) of the patients by telephone survey; 29.9% (124/415) of those patients experienced extraskeletal AEs (most commonly fever and flu-like symptoms [eg, headache, malaise, fatigue, chills, and asthenia]). The percentage of patients reporting AEs was significantly higher for the LFA group than that of the FA group (91.2 vs 19.5; P < 0.001), although factors other than the frequency of treatment might have had a bearing on this finding. All AEs were mild and transient in both groups of patients, and there were no reports of jaw osteonecrosis in either group. It should be noted that although LFA patients received lower doses of pamidronate per infusion than the FA group, they had higher cumulative doses/year. Biochemical variables for the entire study population were compared with baseline measurements, and no significant changes in mean values were observed. Both serum calcium and 25-hydroxy vitamin D levels remained within normal ranges. On the other hand, there was a transient decrease in white blood cell count (WBCC) in 73 (12.0%) patients, and leukopenia was observed in 8 (1.3%) patients. However, 5 of the 6 patients who were leukopenic at the beginning of treatment had normal WBCCs during follow-up. Platelet count decreased significantly in 20 (3.3%) patients, and 5 (0.8%) patients developed thrombocytopenia. Serum creatinine (sCreat) levels increased significantly in 91 (15.0%) patients. This increase was transient and within normal limits (0.6-1.2 mg/dL) in 79 (86.8%) of those patients but persistent in the other 12 (13.2%), all of whom received higher doses of pamidronate or had other risk factors for renal failure such as advanced age, diabetes, multiple myeloma, or an obstructor disease. Baseline sCreat level for 7 of these 12 patients was >1.20 mg/dL. CONCLUSIONS: Pamidronate administered IV was well tolerated when used for treating osteoporosis or other metabolic osteopathies in our study population. The clinical AEs observed with IV pamidronate administration were not serious and hematologic changes were mild, transient, and not associated with dose, time of treatment, or any particular underlying disease. An increase in sCreat level was the most frequent biochemical complication and was found in patients with additional risk factors for renal failure and particular diseases. Whether certain patients with risk factors for osteoporosis may require even fewer IV administrations of the drug is an issue that remains to be elucidated.

Impact of alprazolam in allostatic load and neurocognition of patients with anxiety disorders and chronic stress (GEMA): observational study protocol.

INTRODUCTION: The allostatic load model explains the additive effects of multiple biological processes that accelerate pathophysiology related to stress, particularly in the central nervous system. Stress-related mental conditions such as anxiety disorders and neuroticism (a well-known stress vulnerability factor), have been linked to disturbances of hypothalamo-pituitary-adrenal with cognitive implications. Nevertheless, there are controversial results in the literature and there is a need to determine the impact of the psychopharmacological treatment on allostatic load parameters and in cognitive functions. Gador study of Estres Modulation by Alprazolam, aims to determine the impact of medication on neurobiochemical variables related to chronic stress, metabolic syndrome, neurocognition and quality of life in patients with anxiety, allostatic load and neuroticism. METHODS/ANALYSIS: In this observational prospective phase IV study, highly sympthomatic patients with anxiety disorders (six or more points in the Hamilton-A scale), neuroticism (more than 18 points in the Neo five personality factor inventory (NEO-FFI) scale), an allostatic load (three positive clinical or biochemical items at Crimmins and Seeman criteria) will be included. Clinical variables of anxiety, neuroticism, allostatic load, neurobiochemical studies, neurocognition and quality of life will be determined prior and periodically (1, 2, 4, 8, and 12 weeks) after treatment (on demand of alprazolam from 0.75 mg/day to 3.0 mg/day). A sample of n=55/182 patients will be considered enough to detect variables higher than 25% (pretreatment vs post-treatment or significant correlations) with a 1-ß power of 0-80. t Test and/or non-parametric test, and Pearson's test for correlation analysis will be determined. ETHICS AND DISSEMINATION: This study protocol was approved by an Independent Ethics Committee of FEFyM (Foundation for Pharmacological Studies and Drugs, Buenos Aires) and by regulatory authorities of Argentina (ANMAT, Dossier # 61 409-8 of 20 April 2009), following the law of Habeas Data and psychotherapeutic drug control. TRIAL REGISTRATION NUMBER: GEMA 20811.

Effect of unilateral superior cervical ganglionectomy on mandibular bone in rats.

OBJECTIVE: To assess the effect of local sympathectomy on mandibular bone during tooth eruption in rats. METHODS: The effect of a unilateral superior cervical ganglionectomy (Gx) on morphometry of ipsi- and contralateral mandible and volumetric bone density (as assessed by peripheral computed tomography) was examined 30 days after surgery. RESULTS: Only a few mandibular morphometric parameters decreased significantly after denervation in rats subjected to a unilateral Gx and a contralateral sham-operation. Mandibular volumetric bone density decreased significantly after sympathetic denervation. In a second experiment, carried out under conditions of unilateral unimpeded eruption of incisors performed ipsilaterally or contralaterally to a unilateral Gx, a significant interaction "denervation x type of eruption" was found for most morphometric parameters. Further analysis indicated higher morphometric indexes in denervated mandibles than in the innervated ones under impeded incisor eruption conditions, and lower morphometric indexes in denervated mandibles than in the innervated ones under unimpeded incisor eruption conditions. Unimpeded eruption augmented total volumetric bone density providing the innervation was intact and caused opposite effects on cortical volumetric bone density in the presence of innervation (increase) or absence of innervation (decrease). Trabecular volumetric bone density decreased significantly after sympathetic denervation. CONCLUSION: The results support a role of the sympathetic nervous system in the regulation of bone remodeling.

Mandible and maxilla bone mineral density and threshold analysis studies by pQCT in two edentulous women receiving pamidronate.

The mandible and maxilla of two edentulous women, treated during 25 weeks with oral pamidronate, were monitored by peripheral quantitative tomography (pQCT). Whole bone volumetric mineral density failed to show meaningful variations after treatment. However, an analysis of separated cortical and medullar areas disclosed focal bone loss at the right mandible cortex of patient #1 and at the left maxilla cortex of patient #2. These and other bone sub-regions were further studied by clustering the internal sites with a different degree of bone mineral density, resorting to the mineral threshold analysis provided by the system. Where bone loss was detected, it corresponded to increased loss of the most osteopenic sites, while medium and high-density portions tended to remain unchanged within the region. There were no significant variations in all other regions, or alternatively, minor losses at osteopenic sites were compensated by an increase at high-density portions. Hence, the pQCT system allowed monitoring volumetric bone mineral density at particular sites of interest, discriminating variations at portions with a dissimilar degree of bone volume. Further studies should confirm whether pamidronate exerts a protective effect on sub-regions with previous medium and high degrees of bone mineralization, as suggested by our present findings.

Comparable bioavailability of two esophago-gastric protective formulations containing pamidronate. A cross-over trial in healthy young adults.

The net absorbable amount of pamidronate (APD), according to AUC values assessed in blood, in the customary dose interval of 24 hours, was found to be similar in 8 healthy young volunteers, who received single doses of 3 capsules of 100 mg APD (AUC0-24 = 510.3 +/- 91.5 micrograms/L x h-1) and 2 tablets of 150 mg (AUC0-24 = 580.5 +/- 117.6 micrograms/L x h-1; p = 0.58) in the fasting state. Both formulations present acid-resistant coatings, designed to protect the mucosa of the upper digestive system from contact with insoluble particles of the bisphosphonates. Tmax values were different, and Cmax values presented a wide inter-individual variation, so that both formulations were not strictly bioequivalent. However, these latter factors were of minor clinical importance given the kinetic features of the bisphosphonates. In conclusion, both formulations afforded comparable bioavailability; that is to say that they can provide a sufficient amount of APD within the studied dose interval, so as to cause similar clinical effects.