Anti-annexin V antibody in systemic lupus erythematosus patients with lupus anticoagulant and/or anticardiolipin antibody

We investigated anti-annexin V antibody (aANX) in patients with systemic lupus erythe-matosus (SLE), and correlated to positivity with lupus anticoagulant (LA)/anticardiolipin antibody (aCL). aANX was positive in 12/47 SLE patients (26%), including 7 with β₂-glycoprotein 1 (GPl)-dependent aANX. The positivity of aANX was higher in patients with aCL (19%) and LA/aCL (50%) than in those without LA/aCL (10%). From these results, it is concluded that aANX is an autoantibody closely related to LA/aCL, and can be a possible new risk marker for thrombosis. © 1994 Wiley-Liss, Inc.     

Methanol and Formic Acid Toxicity: Biochemical Mechanisms

Abstract: Metabolism of methanol, methyl ethers, esters and amides give rise to formic acid. This acid is an inhibitor of the mitochondrial cytochrome oxidase causing histotoxic hypoxia. Formic acid is a weaker inhibitor than cyanide and hydrosulphide anions. The body burden of formate in methanol poisoning is high enough to cause acidosis, and other clinical symptoms. Part of the protons can be attributed to formic acid whereas the most significant acid load results from the hypoxic metabolism. The acidosis causes e.g. dilatation of cerebral vessels, facilitation of the entry of calcium ions into cells, loss of lysosomal latency and deranged production of ATP. The latter effect seems to impede parathormone-dependent calcium reabsorption in the kidney tubules. Besides, urinary acidification is affected by formic acid. Its excretion causes continuous recycling of the acid by the tubular cell Cl^?/formate exchanger. This sequence of events may partially explain an accumulation of formate in urine. Occupational exposure to vapours of methanol and formic acid can be quantitatively monitored by urinary formic acid determinations. Formic acid toxicity may prove a suitable model for agents causing histotoxic hypoxia.     

Glucocorticoids do not protect against the lethal effects of experimental heatstroke in baboons

The mortality and neurological morbidity in heatstroke have been attributed to the host's inflammatory responses to heat stress, suggesting that anti-inflammatory therapy may improve outcome. We tested the hypothesis that a high dose of dexamethasone protects baboons against the lethal effects of heatstroke. Ten anesthetized baboons (Papio hamadryas) were assigned randomly to dexamethasone (n = 5) or control group (n = 5). Dexamethasone (2 mg/kg i.v.) was administered in four divided doses every 6 h starting immediately before heat stress and continuing during cooling. All animals were heat-stressed in a prewarmed neonatal incubator at 44 degrees C to 47 degrees C until systolic blood pressure fell less than 90 mmHg and then cooled passively at the ambient temperature. Mortality and neurological morbidity were noted, and biochemical markers of tissue injury/organ dysfunction were determined. Circulating interleukin (IL) 6 and complement components (C3 and C4) were measured sequentially. All heat-stressed animals had systemic inflammation indicated by increased plasma IL-6 and decreased C3 and C4 levels. Dexamethasone attenuated the complement system activation and maintained a higher plasma concentration of IL-6, with a significant augmentation of arterial blood pressure. Dexamethasone did not prevent the occurrence of severe heatstroke but unexpectedly aggravated significantly the tissue injury and multiorgan system dysfunction. Two animals (40%) in the control group and one in the steroid group survived (P > 0.05). Dexamethasone failed to protect the baboons from the lethal effects of heatstroke. These results do not support clinical testing of corticosteroids as beneficial in preventive or therapeutic strategies for the treatment of heatstroke in humans.     

The potential impact of the preparation rich in growth factors (PRGF) in different medical fields

Platelet-rich preparations constitute a relatively new biotechnology for the stimulation and acceleration of tissue healing and bone regeneration. The versatility and biocompatibility of this approach has stimulated its therapeutic use in numerous medical and scientific fields including dentistry, oral implantology, orthopaedics, ulcer treatment, tissue engineering among others. Here we discuss the important progress that has been accomplished in the field of platelet-rich preparations in the last few years. Some of the most interesting therapeutic applications of this technology are discussed as are some of the limitations, future challenges and directions in the field.     

Plasma levels of 17-OH-progesterone and testosterone in patients with varicoceles

In order to study Leydig cell function in patients with varicoceles, we determined plasma levels of the most important testicular steroids, 17-OH-progesterone (17-OH-P) and testosterone (T) in the basal condition and after hCG stimulation. There was a significant inverse linear correlation between age, plasma testosterone, and 17-OH-P (n = 65, r = 0.316, P = 0.01, n = 48, r = 0.532, P = 0.01). This was in contrast to the absence of such correlations in normal men in the same age range. Following hCG stimulation in 16 patients the 17-OH-P/T ratio was significantly increased with respect to normal controls. No correlation was been observed between sperm count and age in varicocele patients. Analysis of variance of 17-OH-P plasma levels between the patients with a sperm count less than 10 million/ml and that of more than 10 million/ml did not reveal any significant difference. These results suggest that the deleterious effects of varicocele on seminiferous tubules and Leydig cells are unrelated. Moreover the increased 17-OH-P/T ratio after hCG stimulation suggests that some enzymatic impairment involving the last steps of testosterone biosynthesis exists in patients with varicoceles. This is evident in middle aged varicocele patients with a premature decrease of plasma levels of testosterone.     

Chronic infiltrative lung diseases: value of gadolinium-enhanced MRI in the evaluation of disease activity--early report

STUDY OBJECTIVE: To determine the value of gadolinium-enhanced MRI in the assessment of disease activity in chronic infiltrative lung diseases (CILDs). DESIGN: Retrospective study. SETTING: University hospital. Materials and Methods: Twenty-five consecutive patients with CILD were studied. The following diseases were diagnosed: sarcoidosis (n = 10), bronchiolitis obliterans organizing pneumonia (n = 3), usual interstitial pneumonia (n = 4), radiation pneumonia (n = 2), desquamative interstitial pneumonia (n = 1), rheumatoid lung (n = 1), vasculitis (n = 1), alveolar proteinosis (n = 1), bronchioloalveolar carcinoma (n = 1), and chronic eosinophilic pneumonia (n = 1). In each patient, the disease activity was assessed by one or more of the following studies: BAL (n = 18), gallium-radioisotope lung scanning (n = 6), serum angiotensin-converting enzyme assay (n = 10), and open lung biopsy (n = 4). T1-weighted breath-hold MRI studies were obtained before and after IV injection of gadolinium. The MRI examinations were analyzed to assess the presence or absence of lesional enhancement. RESULTS: The presence of enhanced pulmonary lesions was seen in 14 patients. All of these patients had active disease. Of the 17 patients with active disease, 14 had enhanced lesions, and 3 had unenhanced lesions. Pulmonary lesions were not enhanced in any patients with inactive disease. The difference was statistically significant (Fisher Exact Test, p < 0.05). CONCLUSION: Gadolinium-enhanced MRI may prove to be a useful tool in assessing disease activity in CILDs.     

Presenteeism according to healthy behaviors, physical health, and work environment

Abstract The objective of this study is to identify the contribution that selected demographic characteristics, health behaviors, physical health outcomes, and workplace environmental factors have on presenteeism (on-the-job productivity loss attributed to poor health and other personal issues). Analyses are based on a cross-sectional survey administered to 3 geographically diverse US companies in 2010. Work-related factors had the greatest influence on presenteeism (eg, too much to do but not enough time to do it, insufficient technological support/resources). Personal problems and financial stress/concerns also contributed substantially to presenteeism. Factors with less contribution to presenteeism included physical limitations, depression or anxiety, inadequate job training, and problems with supervisors and coworkers. Presenteeism was greatest for those ages 30-49, women, separated/divorced/widowed employees, and those with a high school degree or some college. Clerical/office workers and service workers had higher presenteeism. Managers and professionals had the highest level of presenteeism related to having too much to do but too little time to do it, and transportation workers had the greatest presenteeism because of physical health limitations. Lowering presenteeism will require that employers have realistic expectations of workers, help workers prioritize, and provide sufficient technological support. Financial stress and concerns may warrant financial planning services. Health promotion interventions aimed at improving nutrition and physical and mental health also may contribute to reducing presenteeism. (Population Health Management 2012:15:293-301).     

Human ejaculated spermatozoa contain active P450 aromatase

The generation of cytochrome P450 aromatase (P450arom) and estrogen receptor (ER) knockout mice has raised new interest in the physiological role of estrogens in male reproduction. Testicular expression of P450arom, the enzyme that converts androgens into estrogens, has been shown in both somatic and germ cell types in several species, whereas in humans, testicular expression is confined to the somatic cells. The aim of this study was to determine whether P450arom is present in human ejaculated spermatozoa. Using RT-PCR and specific primers, we amplified the highly conserved helical, aromatic, and heme-binding sequences of the conventional human P450arom from RNA isolated from human spermatozoa. Employing a rabbit polyclonal antiserum directed against human placental P450arom, immunoblotting analysis demonstrated aromatase protein expression, which was localized primarily to the tail and midpiece of spermatozoa. Measurement of enzymatic activity using a sensitive (3)H(2)O aromatase assay revealed that activity was enhanced by the 2'-O-dibutyryl cAMP and completely inhibited in the presence of the specific aromatase inhibitor, letrozole. These results represent the first demonstration that human spermatozoa are a potential site of estrogen biosynthesis. The physiological relevance of estrogen synthesis in spermatozoa remains to be elucidated and opens a new area of investigation in male fertility.     

Anti-GMP140 (CD62) autoantibody in a patient with autoimmune thrombocytopenic purpura

The presence of platelet GMP140 (CD62) antibodies was analysed by the MAIPA test in 57 sera from patients with AITP and on platelets from 54 patients with thrombocytopenia of suspected immune origin. A CD62 antibody was found in only one serum. Its specificity was confirmed by an ELISA and a radioimmunoprecipitation procedure using total intact platelets and immuno-purified GMP140. An increased amount of platelet-associated (PA) IgG, due to in vivo fixation of GMP140 and GpIIb/IIIa antibodies, was also found on the patient platelet membrane, suggesting that GMP140 autoantibody may contribute to immune platelet destruction. No increase in PAGMP140 antibody was found on the other 54 platelet suspensions.     

Fetal alcohol exposure and temporal vulnerability: effects of binge-like alcohol exposure on the ventrolateral nucleus of the thalamus

BACKGROUND: Prenatal alcohol exposure disrupts motor performance in affected offspring. The ventrolateral nucleus (VLN) of the thalamus functions to relay information between the cerebellum and motor cortex. Reductions in the size of the thalamus have been found in children with fetal alcohol syndrome, and therefore a rat model system was used to determine whether VLN size and neuronal number were altered by alcohol exposure during development. METHODS: Rat pups were exposed to alcohol in utero during the first 10 days of gestation (first trimester equivalent), the second 10 days of gestation (second trimester equivalent), or the first two trimesters equivalent combined. Some pups were exposed to alcohol in utero during the time of VLN neurogenesis. In addition, offspring from some of the dams treated during the first two trimesters equivalent were reared artificially from postnatal day (P) 4 through P9 (part of the third trimester equivalent) and received binge-like alcohol during this time, resulting in offspring exposed to alcohol during all three trimesters equivalent. Other offspring from untreated dams were reared in the same manner but received alcohol only during the third trimester equivalent. Control animals (nutritional and untreated) were reared for all treatment conditions. All pups were perfused on P10. RESULTS: A unique effect of alcohol treatment was not found for the VLN volume or the number of neural cells within the VLN. However, the period of VLN neurogenesis was found to be sensitive to both alcohol and nutritional control treatments, resulting in significant decreases in the VLN volume and neural cell number. CONCLUSIONS: Motor deficits seen in offspring exposed prenatally to alcohol do not seem to result from direct effects on the structure of the VLN of the thalamus.